HAPpEN: A pragmatic general practitioner-centered obesity management trial in rural Germany integrating multimodal lifestyle interventions

HAPpEN: A pragmatic general practitioner-centered obesity management trial in rural Germany integrating multimodal lifestyle interventions | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article HAPpEN: A pragmatic general practitioner-centered obesity management trial in rural Germany integrating multimodal lifestyle interventions Natascha Schau, Constanze Betz, Anna Weber, Alisa Bader, Laura M. König, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6540216/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background: Elevated prevalence of obesity has increasingly challenged public health systems worldwide, with rural areas being particularly affected. This trial aimed to evaluate the effectiveness of a general practitioner (GP)-centered, multifactorial intervention for obesity management in rural areas. Methods: The HAPpEN trial was a pragmatic, controlled study conducted in six rural primary care practices in Upper Franconia, Germany, with 98 adults (BMI ≥30 kg/m²) enrolled and a 12-month follow-up rate of 62.2%. Exclusion criteria included severe comorbidities restricting physical activity. The intervention combined GP-led behavioral strategies, monthly motivational counselling, nutritional guidance, physical activity, educational workshops, and digital self-monitoring with community activities to foster engagement. The control group received standard care. Primary outcomes included body weight, body mass index (BMI), waist circumference, blood pressure, heart rate, and metabolic parameters such as hemoglobin A1c (HbA1c), fasting glucose, cholesterol, triglycerides, high- and low-density lipoprotein, C-reactive protein and uric acid. Results: The intervention group showed significant reductions in body weight (−5.0 ± 7.7 kg, 95% CI: [-7.24, - 2.83], p< 0.001) and BMI (−1.7 ± 2.6 kg/m², 95% CI: [-2.48, -0.99]), p< 0.001] over 12 months. Waist circumference (−11.5 ± 11.1 cm, 95% CI: [-15.57, -7.34], p< 0.001), systolic blood pressure (−8.3 ± 14.2 mmHg, 95% CI: [-13.22, -3.30], p= 0.04) and HbA1c levels (-3.3 ± 6.2 mmol/mol, 95% CI: [-5.33, -1.30], p< 0.001) significantly improved, with HbA1C normalizing in many cases. A negative correlation was identified between program engagement and weight loss (r s = −0.453, p< 0.001). Conclusion: The GP-centered, multifactorial intervention significantly reduced body weight and improved metabolic health markers in individuals with obesity. Sustained program engagement correlated with enhanced weight loss, underscoring the importance of structured support in rural obesity management. These findings emphasize the key role of GPs in obesity care and suggest the potential for broader application. Trial registration : DRKS00033916, March, 20 th 2024 retrospectively registered. Obesity Primary care Body Mass Index Rural Weight Loss Adults Figures Figure 1 Figure 2 Figure 3 INTRODUCTION The global rise in obesity is a logical outcome of shifting dietary habits and lifestyle patterns as observed in recent decades. The literature highlights not only a significant increase in obesity prevalence but also notable disparities in its incidence across various ethnic groups, socioeconomic positions, and geographical regions ( 1 ). Notably, the proportion of individuals affected by obesity is higher in rural areas compared to urban counterparts ( 2 ), a trend that is particularly pronounced in high-income and industrialized countries, where women, in particular, exhibit a greater prevalence of this inequality. Despite the general extended life expectancy in high-income countries, the rising prevalence of obesity in these regions is strongly associated with comorbidities such as type 2 diabetes, cardiovascular diseases, and cancer, reducing life expectancy by 5.6 to 10.3 years ( 3 ). The reasons for higher obesity prevalence among rural residents remain insufficiently researched. However, weaker structures – including gaps in medical care, preventive programs, and health-promoting infrastructures – seem crucial ( 4 ). Access to healthcare is often limited, with only a few or single facilities serving large districts, creating challenges for both patients and general practitioners (GPs). Patients face long travel distances and waiting times, while GPs must oversee extensive catchment areas, limiting the time available for individual consultations. Despite these challenges, GPs hold a pivotal position in the healthcare system as accessible and trusted primary care providers. They are uniquely positioned to consider the patient’s family and social context, as well as comorbidities, which can enhance patient trust and willingness to act on their advice. This was confirmed by Wrangler et al. ( 5 ), demonstrating that patients view GPs as suitable partner in obesity management and, additionally, GP recommendations positively influences patient’s willingness to lose weight. However, significant deficiencies persist in obesity management, including delayed or incidental diagnosis, inconsistent counseling, infrequent establishment of weight reduction goals, limited referrals to support service, and occasional lack of sensitivity, underscoring the need for effective programs that integrate GP training. Additionally, practitioners report low confidence in the quality of obesity care provided. Schwenke et al.( 6 ) highlighted that doctors rate obesity management in primary care as below average, reinforcing the necessity for systemic improvements and comprehensive intervention strategies that address both GP and patient needs. In rural settings, where doctors benefit from a close familiarity with their patients but often face limited resources, low-threshold and flexible intervention strategies are particularly necessary. The HAPpEN trial explored innovative and scalable strategies for obesity management within a rural, GP-centered framework. By integrating regular GP-led consultations, educational workshops, digital self-monitoring, group-based physiotherapy, and community-based activities, the intervention aims to provide a modular, adaptable, and equitable approach to obesity care. Understanding weight loss dynamics and their broader health implications in rural primary care is critical. This pragmatic trial addresses the following objectives: 1. Effectiveness and Sustainability: Assessing the structured intervention’s impact on body weight and body mass index (BMI) compared to standard obesity treatment. 2. Metabolic and Inflammatory Markers: Evaluating cardiovascular parameters, glucose metabolism, lipid profiles, and systemic inflammation to determine the preventive potential of HAPpEN in reducing the risk of type 2 diabetes or cardiovascular diseases. 3. Physical Function and Medication Adjustment: Investigating changes in joint health, mobility, and medication health as indicators of physiotherapy- and physical activity-induced improvements. 4. Program Adherence and Weight Loss Contribution: Analyzing the relation between program engagement and individual weight loss outcomes. By systematically evaluating these factors, the study provides a comprehensive analysis of the intervention’s effectiveness and feasibility, offering critical insights for future implementation and policy development in rural obesity management. METHODS Aim, design and setting of the study To evaluate the effectiveness of a GP-centered, multifactorial intervention for obesity management in rural, sparsely populated settings, HAPpEN was conducted as a pragmatic trial across six rural primary care practices in Upper Franconia, Germany. Additionally, nine physiotherapists were involved in leading group-based exercise sessions. The enrollment period spanned from May to June 2023. Eligible participants were aged 18 to 65 years with a BMI ≥ 30 kg/m 2 . Comprehensive eligibility criteria are detailed in Supplementary Table 1. Participant recruitment was initiated by physicians during routine GP consultation and checkups, and was further supported by targeted outreach efforts, including informational posters, flyers and public announcements broadcast via local radio. Multifactorial intervention The HAPpEN program adheres to current clinical guidelines following the 5A model ( 7 , 8 ) and, emphasizing individualized care. Baseline assessments included (self-reported) medical history, physical exams, and laboratory testing to evaluate health status. GPs, serving as central coordinators, conducted follow-up evaluations at six (T6) and 12 (T12) months to monitor changes and potential risk factors. Primary outcomes comprised body weight, BMI, waist circumference, blood pressure, heart rate and metabolic parameters including hemoglobin A1c (HbA1c), fasting glucose, cholesterol, triglycerides, high- and low-density lipoproteins (HDL/LDL), C-reactive protein (CrP) and uric acid. Body weight and BMI were recorded monthly, while waist circumferences, blood pressure, heart rate and laboratory analysis were assessed at baseline and at follow-ups after six and 12 months, alongside physical exams of the heart, lungs, abdomen, joints, and spine to guide exercise recommendations and track progress. Ergometry was conducted following standardized protocols to assess physical fitness and exercise-induced blood pressure responses. Secondary outcomes included assessments of quality of life, disease burden conceptualized as wellbeing, nutritional status, physical activity, health literacy, social interaction, and digital therapy support. The results of these assessments will be reported separately. Throughout the trial, GPs developed individualized therapy plans focusing on nutrition, physical activity and behavioural modification while providing continuous motivational support. Participants received monthly in-office monitoring by their GP, supplemented by structured physiotherapy sessions and app-based self-monitoring. Education and social interaction were reinforced through digital learning modules and in-person activities, including cooking workshops and hiking events, fostering community engagement and sustainable health behaviour changes. The full trial setup, intervention and the description of the trial population is provided in the study protocol ( 9 ). Control patients Patients receiving current standard care (n = 58) including a combination of nutritional therapy, exercise, and behavioural therapy ( 8 , 7 ) for obesity, administered by the same GPs within the same timeframe served as controls. In this context, body weight and BMI of these patients were analysed. However, these patients did not receive the structured education and monthly counselling on nutrition, physical activity or behaviour provided in the HAPpEN intervention program. Statistical Analysis All statistical calculations including descriptive statistics were performed using SPSS version 29. The comparison of the social anamnesis characteristics between the baseline population and the completers was employed either using a two-sample t-test or a Pearson Chi-squared test. Changes within the intervention group over time were tested using a one-way analysis of variance. For weight and BMI assessments, a two-way analysis of variance was conducted analyzing the effects between the intervention group and a control cohort over time. The post-hoc comparisons were performed using the Bonferroni test. For joint-related outcomes, Cochran’s Q test and Friedmann test were applied. Spearman correlation was conducted to examine the association between time spent on intervention and weight reduction (T0 - T12). Normality was assessed by graphical inspection or using the Shapiro-Wilk test and variance homogeneity was checked by using Levene’s test. Statistical significance was set at p < 0.05. Artificial intelligence statement In the drafting of this manuscript, ChatGPT was employed to assist with spelling correction and language refinement. RESULTS Trial and population characteristics Between May and June 2023, 98 eligible participants representing the baseline cohort (T0) were enrolled in the trial (Fig. 1 ). They were all German, with a mean age of 46.9 ± 11.8 years. The majority of patients were female (74.1%, see Supplementary Table 2) and the BMI was 40.1 ± 6.1 kg/m², with 48.5% classified as having grade III obesity (BMI ≥ 40 kg/m²) ( 9 ). A total of 61 patients (62.2%) completed the 12 months follow-up (Fig. 1 ). Sociodemographic factors or previous years spent on weight reduction were unrelated to dropout, as a comparison of these characteristics between the dropouts and final population showed no significant differences (see Supplementary Table 2). Based on the clinical record of the baseline population, the prevalence of hypertension was notably high at 59.6% (see Supplementary Table 3). Dyslipidemias and type 2 diabetes were also prevalent, affecting 21.3% and 19.1% of participants, respectively, while latent diabetes was reported in 12.8%. Obesity-related conditions were common, including venous insufficiency (25.5%), obstructive sleep apnea (3.2%), and lipedema (2.1%). Additional diagnoses included hypothyroidism (8.5%), asymptomatic hyperuricemia (11.7%), gastroesophageal reflux disease (10.6%) and depressive episodes (11.7%). Musculoskeletal disorders were also frequent, with gonarthrosis (12.8%), coxarthrosis (7.4%), degenerative spinal diseases (10.6%), and chronic back pain, including radiculopathy and lumbago (17.0%). These findings highlight the substantial burden of metabolic, cardiovascular, psychiatric, and musculoskeletal comorbidities within this cohort, emphasizing the necessity for comprehensive and multidisciplinary management strategies to address these interconnected health challenges. Notably, participants’ self-assessment of their health status, as measured by questionnaire ( 9 ), showed only minor deviations from the documented clinical diagnoses, indicating a accurate perception of their own health conditions. Clinical outcome Comparisons to control patients: Changes in body weight and BMI In the completers analysis, the intervention group exhibited a higher mean body weight (+ 6.8 kg, 95% CI: [-1.07, 14.62], p = 0.090) and BMI (+ 2.3 kg/m 2 , 95% CI: [0.08; 4.55], p = 0.042) at baseline compared to the control group, with a greater proportion of participants classified as having obesity grade III (+ 14.9%) and grade II (+ 5.4%) (see Table 1 ). A two-way analysis of variances yielded a significant time x group interaction effect (F(1.77, 206.47) = 8.52, p < 0.001, ηp 2 = 0.07), indicating greater weight reduction in the intervention group compared to controls (see Table 1 ). Over the course of the trial, the intervention group experienced a significant reduction in body weight, with a mean loss of -5.4 ± 6.5 kg from T0 to T6 (95% CI: [-7.33, -3.40], p < 0.001) and − 5.0 ± 7.7 kg from T0 to T12 (95% CI: [-7.24, -2.83], p < 0.001). Weight loss was most pronounced in the first six months, followed by weight maintenance between T6 and T12 (+ 0.3 kg, 95% CI: [-1.26, 1.91], p = 1.000), despite seasonal challenges such as Christmas and New Year, during which a temporary weight increase was observed (see Supplementary Fig. 1). By T6, 42.6% of participants in the intervention group achieved ≥ 5% and 9.8% achieved ≥ 10% weight loss, compared to 16.4% and 19.7% by T12 (see Table 1 ). In contrast, no significant weight changes were observed in the control group, with an average weight reduction of -1.2 ± 6.1 kg from T0 to T6 (95% CI: [-3.23, 0.80, p = 0.434) and − 1.0 ± 6.4 kg from T0 to T12 (95% CI: [-3.29, 1.24, p = 0.820). Similarly, a significant time x group interaction effect was noted for BMI (F(1.77, 207.17) = 8.73, p < 0.001, ηp 2 = 0.07), confirming a more pronounced BMI reduction in the intervention group. BMI in the HAPpEN group decreased significantly by -1.8 ± 2.2 kg/m 2 from T0 to T6 (95% CI: [-2.48, -0.99], p < 0.001) and by -1.7 ± 2.6 kg/m 2 from T0 to T12 (95% CI: [-2.48, -0.99], p < 0.001), with minimal changes between T6 and T12. By T12, the intervention group showed a shift towards lower BMI classes, with an increase in participants classified as overweight (+ 6.6%) and reductions in obesity grade II (-6.5%) and grade III (-3.3%) (see Table 1 and Fig. 2 A). Changes over time in HAPpEN patients: Waist circumference, blood pressure, cardiovascular fitness and blood parameters In alignment with weight loss, waist circumference significantly decreased over time among participants enrolled in the HAPpEN intervention group. The mean waist circumference declined by -8.4 ± 10.8 cm from T0 to T6 (95% CI: [-12.42, -4.40], p < 0.001) and further by -11.5 ± 11.1 from T0 to T12 (95% CI: [-15.57, -7.34], p < 0.001; F(1.35, 59.21) = 35.59, ηp 2 = 0.45) (see Table 2 ). Additionally, systolic blood pressure showed significant reductions by T12 (systolic: F(1.77, 86.70) = 6.15, p = 0.04, ηp 2 = 0.11). During physical exertion, significant reductions in systolic diastolic blood pressure were observed from T0 to T6 at 75 W(systolic: F(2, 78) = 7.65, p < 0.001, ηp 2 = 0.16; diastolic: F(2, 78) = 7.09, p = 0.01, ηp 2 = 0.15) and at 125 W (systolic: F( 2 , 38 ) = 3.94, p = 0.028, ηp 2 = 0.17; diastolic: F( 2 , 38 ) = 3.80, p = 0.031, ηp 2 = 0.17). Additionally, the mean maximal wattage achieved during ergometry assessments increased by + 6.7 ± 21.2 W (95% CI: [-1.31, 14.80], p = 0.129) at T6 (see Table 2 ), reflecting improved cardiovascular fitness. Conversely, heart rate did not exhibit statistically significant changes, nor did glucose, uric acid, triglycerides, cholesterol, HDL- and LDL-cholesterol over the trial period (see Table 3 ). However, percental HbA1c level decreased significantly by -0.3 ± 0.6% both from T0 to T6 and T0 to T12 (T6: 95% CI: [-0.47, -0.09], T12: 95% CI: [-0.49, -0.12], F(1.19, 67.91) = 13.39, p < 0.001, ηp 2 = 0.19) (see Table 3 and Fig. 2 B). Similarly, absolute HbA1c decreased by -3.3 ± 6.2 mmol/mol at T12 (95% CI: [-5.33, -1.30], F(1.19, 68.00) = 13.55, p < 0,001, ηp 2 = 0.19) (see Table 3 ). The significant reduction in HbA1c levels, alongside decreases in weight, BMI, and blood pressure, indicates that HAPpEN contributed to improved glycemic control, lowering the risk of developing type 2 diabetes. In line, the improvement in ergometry parameters enhanced cardiovascular fitness, further supporting diabetes prevention. Comorbidities and Medication Use As shown in Table 4 , the knee and shoulder joints emerged as the most frequently affected sites of pain among individuals with obesity. The hips also demonstrated a comparatively high prevalence of pain, while pain in the fingers, wrists, ankles, toe joints and elbows was reported less frequently. The proportion of participants reporting overall physical complaints was pretty high, but significantly decreased over trial time, from 81.6% at baseline (T0) to 65.3% at T12 (Q( 2 ) = 8.59, p = 0.014). In contrast, the prevalence of joint complaints over the past 12 months as well as in the last 24 hours remained stable. In addition, joint health metrics remained unchanged and no significant changes in the medication regimes were seen for the participants either (see Table 5 ). All medication categories showed stable usage patterns during the trial, with minimal fluctuations. Thus, the proportion of participants on antihypertensives as the most prevalent medication remained 60.3–63.8%, while diuretics and statins as the second most common drugs were consistent at 31.0–32.8% and 19.0%. Given the significant reductions in body weight, BMI, waist circumference, blood pressure and HbA1C observed, the lack of change in joint complaints and medication use suggests that improvements in metabolic health may not immediately translate into measurable reduction in musculoskeletal burden. Engagement with HAPpEN program and association with weight loss A Spearman correlation was conducted to assess the relationship between participation time in HAPpEN as an indicator for program engagement and individual weight loss in percent from T0 to T12. The analysis showed a significant negative correlation [r s = − 0.45, p < 0.001, n = 51) indicating that higher weekly participation in the HAPpEN program was associated with greater weight loss over the trial period (see Fig. 3 ). This finding suggests that increased engagement in the intervention contributes to enhanced weight reduction outcomes, supporting the effectiveness of consistent participation in structured health programs. Table 1 Clinical parameters of participants in HAPpEN intervention group and control cohort. parameters groups T0 [95% CI] or (n) T6 [95% CI] or (n) T12 [95% CI] or (n) T0 to T6 [95% CI] T6 to T12 [95% CI] T0 to T12 [95% CI] time effect time x group effect Weight (kg) Controls HAPpEN 111.8 ± 20.2 [106.18, 117.41] 118.6 ± 22.8 [113.09, 124.05] 110.6 ± 19.3 [105.06, 116.10] 113.0 ± 22.9 [107.82, 118.59] 110.8 ± 20.1 [105.03, 116.51] 113.5 ± 23.8 [107.94, 119.13] -1.2 ± 6.1 [– 3.23, 0.80] -5.4 ± 6.5 [-7.33, -3.40] 0.2 ± 5.2 [-1.43, 1.82] 0.3 ± 5.0 [-1.26, 1.91] -1.0 ± 6.4 [-3.29, 1.24] -5.0 ± 7.7 [-7.24, -2.83] < 0.001 < 0.001 Weight loss (%) 5%/ 10% Controls HAPpEN 13.8 ( 8 )/ 1,7 ( 1 ) 42.6 ( 26 )/ 9.8 ( 6 ) 13,8 ( 8 )/ 3,4 ( 2 ) 16.4 ( 10 )/ 19.7 ( 12 ) BMI (kg/m²) Controls HAPpEN 38.0 ± 5.8 [36.39, 39.59] 40.3 ± 6.5 [38.75, 41.86] 37.6 ± 5.4 [36.00, 39.16] 38.5 ± 6.7 [36.94, 40.01] 37.6 ± 5.7 [36.00, 39.28] 38.6 ± 6.8 [36.97, 40.17] -0.4 ± 2.1 [-1.10, -0.29] -1.8 ± 2.2 [-2.48, -0.994] 0.1 ± 1.8 [-0.49, 0.61] 0.1 ± 1.7 [-0.44, 0.63] -0.4 ± 2.1 [-1.12, 0.41] -1.7 ± 2.6 [-2.48, -0.99] < 0.001 < 0.001 BMI classes (%) Overweight Obesity grade I Obesity grade II Obesity grade III Controls HAPpEN 0.0 (0) 44.8 ( 26 ) 24.1 ( 14 ) 31.0 ( 18 ) 0.0 (0) 24.6 ( 15 ) 29.5 ( 18 ) 45.9 ( 28 ) 0.0 (0) 43.1 ( 25 ) 22.4 ( 13 ) 34.5 ( 20 ) 6.6 ( 4 ) 29.5 ( 18 ) 26.2 ( 16 ) 37.7 ( 23 ) 5.2 ( 3 ) 37.9 ( 22 ) 24.1 ( 14 ) 32.8 ( 19 ) 6.6 ( 4 ) 27.9 ( 17 ) 23.0 ( 14 ) 42.6 ( 26 ) Data are shown as mean ± standard deviation at baseline (T0), after six (T6) and twelve months (T12) including statistical analysis performed using a two-way analysis of variances across time points (T0- T12). The HAPpEN Intervention group is represented by 61 participants, the control cohort by 58 participants. BMI: body mass index Table 2 Clinical parameters of participants in HAPpEN intervention group. parameters T0 [95% CI] or (n) T6 [95% CI] or (n) T12 [95% CI] or (n) T0 to T6 [95% CI] T6 to T12 [95% CI] T0 to T12 [95% CI] time effect n Abdominal circumference (cm ) 123.7 ± 14.3 [119.43, 128.01] 115.3 ± 14.2 [111.05, 119.57] 112.3 ± 14.7 [107.84, 116.69] -8.4 ± 10.8 [-12.42, -4.40] -3.0 ± 5.2 [-4.97, -1.12] -11.5 ± 11.1 [-15.57, -7.34] < 0.001 45 BP (mmHg) systolic diastolic 136.1 ± 14.0 [132.13, 140.07] 85.2 ± 8.9 [82.67, 87.77] 130.3 ± 15.6 [125.90, 134.78] 83.6 ± 11.4 [80.36, 86.84] 127.8 ± 12.8 [124.21, 131.47] 80.9 ± 9.4 [78.20–83.52] -5.8 ± 19.6 [-12.62, 1.10] -1.6 ± 13.3 [-6.28, 3.04] -2.5 ± 17.1 [-8.49, 3.49] -2.7 ± 13.9 [-7.61, 2.13] -8.3 ± 14.2 [-13.22, -3.30] -4.4 ± 9.6 [-7.73, -0.99] 0.004 0.055 50 Ergometry Maximum W 139.8 ± 30.1 [130.51, 149.03] 146.5 ± 35.2 [135.69, 157.34] 144.2 ± 30.3 [134.86, 153.51] 6.7 ± 21.2 [-1.31, 14.80] -2.3 ± 23.7 [-11.32, 6.67] 4.4 ± 22.7 [-4.22, 13.07] 0.144 43 Ergometry classification % < 125 watts ≥ 125 watts 15.8 ( 9 ) 84.2 (48) 14.3 ( 7 ) 85.7 ( 42 ) 19.0 ( 11 ) 81.0 (47) BP (mmHg) – 75 W systolic diastolic 162.8 ± 20.9 [156.07, 169.44] 92.1 ± 12.6 [88.02, 96.08] 151.0 ± 12.8 [146.87, 155.08] 84.5 ± 8.9 [81.69, 87.36] 155.8 ± 17.8 [150.07, 161.44] 87.5 ± 12.7 [83.45, 91.55] -11.8 ± 20.0 [-19.70, -3.85] -7.5 ± 13.9[-13.04, -2.01] 4.8 ± 17.1 [-1.99, 11.54] 3.0 ± 10.2 [-1.08, 7.03] -7.0 ± 20.2 [-14.98, 0.98] -4.6 ± 13.7 [-9.96, 0.86] < 0.001 0.001 40 BP (mmHg) – 100 W systolic diastolic 172.5 ± 22.7 [163.70, 181.31] 94.5 ± 10.0 [90.58, 98.36] 164.0 ± 16.2 [157.71, 170.29] 89.6 ± 10.9 [85.41, 93.85] 166.8 ± 27.6 [156.06, 177.44] 90.4 ± 17.8 [83.54, 97.32] -8.5 ± 22.0 [-19.09, 2.09] -4.8 ± 9.2 [-9.27, -0.41] 2.8 ± 25.2 [-9.43, 14.93] 0.8 ± 14.8 [-6.36, 7.96] -5.8 ± 27.3 [-18.94, 7.44] -4.0 ± 14.6 [-11.07, 2.99] 0.194 0.135 28 BP (mmHg) – 125 W systolic diastolic 187.8 ± 18.9 [178.91, 196.59] 100.0 ± 12.5 [94.17, 105.83] 173.8 ± 17.5 [165.58, 181.92] 92.5 ± 8.4 [88.59, 96.41] 184.5 ± 22.9 [173.77, 195.23] 96.5 ± 16.1 [88.94, 104.06] -14.0 ± 24.6 [-28.46, 0.46] -7.5 ± 12.0 [-14.53, -0.47] 10.8 ± 24.5 [-3.64, 25.14] 4.0 ± 11.1 [-2.50, 10.50] -3.3 ± 20.7 [-15.38, 8.89] -3.5 ± 13.4 [-11.36, 4.36] 0.028 0.031 20 BP (mmHg) – 150 W systolic diastolic 192.1 ± 25.9 [175.63, 208.53] 96.3 ± 12.1 [88.57, 103.93] 177.9 ± 18.3 [166.31, 189.53] 90.0 ± 8.8 [84.42, 95.59] 185.8 ± 22.3 [171.64, 200.03] 87.4 ± 5.5 [83.93, 90.90] -14.2 ± 19.6 [-30.15, 1.82] -6.3 ± 10.5 [-14.78, 2.28] 7.9 ± 19.7 [-8.13, 23.96] -2.6 ± 12.4 [-12.65, 7.48] -6.3 ± 22.5 [-24.55, 12.05] -8.8 ± 14.5 [-20.60, 2.94] 0.080 0.063 12 Heart rate (beats/min) 79.1 ± 12.0 [75.63, 82.58] 77.8 ± 10.2 [74.78, 80.72] 75.9 ± 10.9 [72.70, 79.01] -1.4 ± 14.3 [-6.48, 3.77] -1.9 ± 10.5 [-5.65, 1.86] -3.3 ± 14.2 [-8.33, 1.83] 0.232 48 Data are shown as mean ± standard deviation at baseline (T0), after six (T6) and twelve months (T12) including statistical analysis performed using a one-way analysis of variances across time points (T0- T12). BP: blood pressure, W: wattage Table 3 Laboratory parameters of participants in the HAPpEN intervention group. parameters Ref. T0 [95% CI] T6 [95% CI] T12 [95% CI] T0 to T6 [95% CI] T6 to T12 [95% CI] T0 to T12 [95% CI] time effect n Glucose (mg/dl) 60–100 102.2 ± 23.6 [96.11, 108.22] 97.0 ± 19.6 [92.01, 102.02] 100.7 ± 19.6 [95.65, 105.67] -5.1 ± 18.8 [-11.07, 0.78] 3.6 ± 14.5 [-0.94, 8.22] -1.5 ± 17.1 [-6.90, 3.88] 0.054 61 HbA1C ( %) 4.5–5.6 5.9 ± 0.9 [5.71, 6.17] 5.7 ± 0.5 [5.53, 5.80] 5.6 ± 0.5 [5.51, 5.76] -0.3 ± 0.6 [-0.47, -0.09] -0.03 ± 0.21 [-0.10, 0.04] -0.3 ± 0.6 [-0.49, -0.12] < 0.001 58 HbA1C (mmol/mol) 26.0–38.0 41.3 ± 9.5 [38.81, 43.83] 38.4 ± 5.7 [36.88, 39.87] 38.0 ± 5.1 [36.7, 39.35] -2.9 ± 6.4 [-5.02, -0.87] -0.4 ± 2.2 [-1.10, 0.36] -3.3 ± 6.2 [-5.33, -1.30] < 0.001 58 Uric Acid (mg/dl) 7.5 ± 11.1 [4.69, 10.32] 5.8 ± 1.4 [5.46, 6.20] 5.8 ± 1.4 [5.47, 6.20] -1.6 ± 10.6 [-5.02, 1.76] 0.01 ± 0.90 [-0.28, 0.29] -1.6 ± 10.6 [-4.99, -1.74] 0.241 60 Uric Acid (mg/dl) - female 2.4–5.7 7.8 ± 13.7 [3.32, 12.23] 5.4 ± 1.2[5.03, 5.83] 5.5 ± 1.4 [5.01, 5.93] -2.4 ± 13.1 [-7.62, 2.93] 0.4 ± 0.8 [-0.27, 0.36] -2.3 ± 13.1 [-7.56, 2.95] 0.276 39 Uric Acid (mg/dl) - male 3.4-7.0 7.0 ± 1.6 [6.23, 7.87] 6.7 ± 1.4 [5.98, 7.44] 6.7 ± 1.1[6.11, 7.24] -0.3 ± 1.8 [-1.51, 0.84] 0.04 ± 1.12 [-0.69, 0.76] -0.4 ± 1.4 [-1.25, 0.51] 0.519 17 Triglycerides (mg/dl) < 150 154.4 ± 85.5 [132.31, 176.49] 140.1 ± 76.0 [121.26, 160.51] 150.1 ± 100.7 [124.10, 176.10] -13.5 ± 55.9 [-31.29, 4.26] 9.2 ± 71.5 [-13.53, 31.97] -4.3 ± 70.3 [-26.68, -18.08] 0.276 60 Cholesterol (mg/dl) < 200 196.3 ± 42.3 [85.39, 207.24] 196.5 ± 42.8 [185.42, 207.54] 198.3 ± 48.7 [185.67, 210.83] 0.2 ± 19.5 [-6.02, 6.36] 1.8 ± 27.6 [-7.02, 10.55] 1.9 ± 28.5[-7.14, 11.01] 0.211 60 HDL Cholesterol (mg/dl) > 45 52.0 ± 16.2 [47.78, 56.13] 53.0 ± 13.9 [49.39, 56.58] 52.4 ± 15.8 [48.32, 56.48] 1.0 ± 7.0 [-1.20, 3.27] -0.6 ± 7.1 [-2.84, 1.68] -0.5 ± 8.1 [-3.02, 2.12] 0.559 60 LDL Cholesterol (mg/dl) < 160 116.8 ± 34.6 [107.82, 125.72] 118.5 ± 36.0 [109.14, 127.76] 118.1 ± 40.1 [107.77, 128.46] 1.7 ± 17.1 [-3.75, 7.12] -0.3 ± 24.2 [-8.02, 7.36] 1.4 ± 26.3 [-7.01, 9.71] 0.183 60 CrP (mg/l) < 5.0 5.8 ± 5.5 [4.39, 7.23] 5.3 ± 5.0 [4.05, 6.62] 4.4 ± 3.8 [3.37, 5.35] -0.5 ± 3.7 [-1.66, 0.71] -1.0 ± 3.7 [-2.14, 0.20] -1.5 ± 4.4 [-2.84, -0.06] 0.017 60 Data are shown as mean ± standard deviation at baseline (T0), after six (T6) and twelve months (T12), including statistical analysis performed using a one-way analysis of variances across time points (T0- T12). HbA1C: hemoglobin A1C, HDL: high-density lipoprotein, LDL: low-density lipoprotein, CrP: C-reactive protein Table 4 Descriptive analysis of self-reported joint complaints in the HAPpEN intervention group. T0 T6 T12 p-value Cochran-Q Chi-squared test df n Overall physical complaints (%) 81.6 63.3 65.3 0.014 8.59 - 2 49 Joint complaints last 12 months (%) 77.6 81.6 69.4 0.280 2.55 - 2 Joint complaints last 24 hours (%) 46.8 44.7 38.3 0.522 1.30 - 2 47 Pain in the last 24 hours (%) Light/Moderate/Severe Shoulder Left side: 14.5/ 7.3/ 0.0 Right side: 16.4/ 5.5/ 1.8 Left side: 10.9/ 7.3/ 7.3 Right side: 14.5/ 7.3/ 3.6 Left side: 20.0/ 12.7/ 3.6 Right side: 20.0/10.9/ 1.8 0.122 0.460 - 4.21 1.56 2 2 55 Elbow Left side: 1.8/1.8/ 0.0 Right side: 5.5/ 1.8/ 1.8 Left side: 10.9/3.6/ 0.0 Right side: 10.9/ 1.8/ 0.0 Left side: 9.1/ 1.8/ 0.0 Right side: 9.1/ 1.8/ 1.8 0.116 0.544 - 4.31 1.22 2 2 Wrist Left side: 5.5/ 3.6/ 0.0 Right side: 3.6/ 7.3/ 0.0 Left side: 14.6/ 3.6/ 1.8 Right side: 14.5/ 5.5/ 0.0 Left side: 16.4/ 3.6/ 0.0 Right side: 14.5/ 3.6/ 0.0 0.070 0.414 - 5.31 1.76 2 2 Finger joint Left side: 10.9/ 5.5/ 0.0 Right side: 9.1/ 7.3/ 0.0 Left side: 10.9/ 1.8/ 0.0 Right side: 10.9/ 1.8/ 0.0 Left side: 12.7/ 3.6/ 0.0 Right side: 12.7/ 7.3/ 0.0 0.670 0.205 - 0.80 3.17 2 2 Hip Left side: 7.3/ 7.3/ 3.6 Right side: 10.9/ 3.6/ 7.3 Left side: 7.3/ 14.5/ 0.0 Right side: 5.5/ 10.9/ 3.6 Left side: 12.7/ 9.1/ 1.8 Right side: 9.1/ 10.9/ 1.8 0.581 0.880 - 1.09 0.26 2 2 Knee Left side: 14.5/ 12.7/ 1.8 Right side: 18.2/ 12.7/ 1.8 Left side: 9.1/ 18.2/ 1.8 Right side: 10.9/ 14.5/ 1.8 Left side: 3.6/ 20.0/ 3.6 Right side: 5.5/ 20.0/ 3.6 0.781 0.694 - 0.49 0.73 2 2 Ankle Left side: 9.1/ 7.3/ 0.0 Right side: 7.3/9.1/ 0.0 Left side: 10.9/ 10.9/ 0.0 Right side: 9.1/ 12.7/ 0.0 Left side: 9.1/ 7.3/ 0.0 Right side: 7.3/ 7.3/ 1.8 0.469 0.510 - 1.51 1.35 2 2 Toe joint Left side: 3.6/ 5.5/ 0.0 Right side: 3.6/ 3.6/ 0.0 Left side: 10.9/ 1.8/ 1.8 Right side: 12.7/ 1.8/ 0.0 Left side: 7.3/ 5.5/ 0.0 Right side: 7.3/ 5.5/ 0.0 0.674 0.307 - 0.79 2.36 2 2 Data are shown as completers analysis at baseline (T0), after six (T6) and twelve months (T12), including statistical analysis performed using either Cochran-Q or Friedmann test. While significant improvements in general physical complaints were observed during the trial, no significant changes were shown in joint complaints. Table 5 Descriptive and statistical analysis of medications from participants in the HAPpEN intervention trial. Medication Final Population (%) T0 T6 T12 p-value Cochran-Q df Antihypertensives (Ramipril, Amlodipine, Bisoprolol, Valsartan, Enalapril) 60.3 60.3 63.8 0.641 0.89 2 Diuretics (Furosemide, Piretanide, Torasemide, Hydrochlorothiazide) 31.0 32.8 32.8 0.846 0.33 Antidiabetic/Biguanides (Metformin) 13.8 15.5 15.5 0.717 0.67 DPP-IV Inhibitors (Linagliptin, Saxagliptin, Sitagliptin, Vildagliptin) 0.0 1.7 0.0 0.368 2.00 GLP Analogues (Dulaglutid, Exenatid, Liraglutid) 5.2 5.2 3.4 0.368 2.00 SGLT2 Inhibitors (Empagliflozin, Dapagliflozin) 5.2 6.9 5.2 0.717 0.67 PPI (Omeprazole, Pantoprazole, Esomeprazole) 15.5 12.1 10.3 0.368 2.00 Statins (Atorvastatin, Rosuvastatin, Simvastatin) 19.0 19.0 19.0 1.000 0.00 Cholesterol Absorption Inhibitors (Ezetimibe) 5.2 3.4 5.2 0.368 2.00 Cholesterol Synthesis Inhibitors (Bempedoic Acid) 1.7 0.0 1.7 0.368 2.00 Bile Acid Sequestrants (Cholestyramine) 1.7 1.7 1.7 1.000 0.00 Analgetics (Ibuprofen, Etoricoxib, Celecoxib, Metamizole, Diclofenac) 12.1 8.6 8.6 0.513 1.33 Anticonvulsants (Pregabalin) 1.7 1.7 1.7 1.000 0.00 Psychotropic Drugs Tricyclic Antidepressants (Amitriptyline, Clomi-pramine, Desipramine, Nortriptyline) Selective Serotonin Reuptake Inhibitors (Citalopram, Sertraline, Fluoxetine) Serotonin-Norepinephrine Reuptake Inhibitors (Venlafaxine, Duloxetine) Norepinephrine-Dopamine Reuptake Inhibitor (Bupropion) 13.8 13.8 17.2 0.264 2.67 Antipsychotics/Neuroleptics (Olanzapine, Clozapine, Quetiapine, Ziprasidone, Aripiprazole) 1.7 1.7 1.7 1.000 0.00 Information on medication was obtained from the patient’s medication plans (n = 58). Anticonvulsants (Valproate, Carbamazepine, Lamotrigine, Topiramate), psychotropic drugs (Lithium), and steroids were not consumed by any of the participants and therefore not included in the table. For statistical analysis Cochran’s Q test was applied. DISCUSSION The present trial examined the impact of a GP-centered, multifactorial intervention focusing on exercise and nutrition on weight loss and metabolic health markers in rural populations, where obesity prevalence has been notably high ( 10 , 4 , 11 , 2 ). Our findings show significant reductions in body weight, BMI, waist circumference and improved HbA1c levels from enrollment to trial completion. The most significant weight loss was observed between T0 and T6, aligning with evidence that the initial phase of weight reduction is typically the most pronounced ( 12 , 13 ). Thereafter, weight maintenance became predominant, despite external challenges such as the holiday season, during which a temporary weight increase was observed but subsequently reversed, indicating adherence resilience ( 13 – 15 ). In contrast but consistent with literature ( 12 ), the control group undergoing standard treatment did not exhibit significant weight changes throughout the study period, underscoring the efficacy of the intervention program. With the significant reductions in waist circumference and HbA1c next to body weight and BMI, the intervention's potential to lower the risk of type 2 diabetes and in glycemic improvements is highlighted, too ( 16 ). Improvements in blood pressure and ergometry parameters further suggest benefits for long-term cardiovascular health. These findings align with previous research and confirm the effectiveness of primary care interventions in managing obesity and related comorbidities in rural populations ( 17 ). The HAPpEN trial effectively addressed rural healthcare challenges by integrating structured follow-ups with already familiarized GPs, local grouped physiotherapy, and digital self-monitoring, demonstrating its viability as an obesity management model in underserved areas ( 18 ). Moreover, the trial enabled dynamic adjustments to dietary and exercise recommendations, ensuring the program remained accessible in a sparsely populated rural real-world setting and personalized to each participant's needs. Higher participation frequency was associated with greater weight loss, supporting findings that show at least 12 contacts with the primary care provider seem valuable for sustainable outcomes ( 17 ). The strong correlation between program engagement and weight loss also highlights the value of structured (primary care) lifestyle interventions ( 19 ). Its multifactorial approach proved effective, seen in a similar way in the past compared to single-component interventions, reinforcing the importance of continuous participation and engagement, including behavioral counseling, nutritional counseling and exercise guidance as well as social events and support. The potential benefit of GP-centered support may be especially valuable for rural populations that face unique barriers for weight-loss or lifestyle-modification programs, including limited healthcare resources, longer travel distances, and fewer community-based health initiatives ( 20 , 21 , 4 , 22 ) by offering accessible, long-term support. Following previous research ( 5 , 27 , 35 , 36 ), the perspectives of GPs on obesity therapy and their role within this domain must be considered to enhance the effectiveness of treatment strategies. Not only the centrality of the GP within the patient’s view as well as the possibility to reach and motivate many, but also the current update of therapeutic guidelines goes hand in hand with our results, emphasizing the critical role of GPs in coordinating comprehensive care for patients with obesity. Bridging the gap between GP visits in rural areas, our trial also incorporated an app for self-monitoring and management. This aligns with previous research and the current German obesity guidelines, showing increased efficiency of app-based interventions especially in underserved areas ( 23 , 24 ) and therefore now recognizing digital therapeutic tools as essential components of obesity treatment, rather than optional interventions ( 7 , 25 ). By promoting self-regulation and providing personalized guidance, digital tools like the app enhance adherence and outcomes. The app fosters a personalized approach enabling participants to track their food intake, physical activity, and health metrics as well as tailored adjustments based on individual progress and needs. The app’s role in fostering self-regulation and continuous support enhances adherence and long-term results ( 26 ). However, digital exclusion may limit the app’s effectiveness, as individuals with limited digital literacy may face challenges, potentially reducing the program's overall impact ( 27 – 29 ). Our findings align with previous studies that demonstrate the efficacy of multifactorial lifestyle interventions with (digital) self-management, social events and regular check-ups in promoting weight loss, cardiovascular and metabolic improvements. Notably, this trial differs from others ( 30 – 36 ) by focusing on the percentage change in clinical parameters for each individual, rather than averaging the parameters at a specific time point across the entire cohort. This approach allows for a more nuanced understanding of individual progress and the effectiveness of the intervention over time. Despite these strengths, the study's lack of a no-intervention control group represents a limitation, especially when compared to randomized controlled trials ( 37 ), where such a control group allows for clearer conclusions regarding the intervention's specific effects. Unlike many previous studies conducted in urban or well-resourced settings, this trial specifically targeted rural populations, indicating that structured, GP-centered interventions can be effectively adapted to rural contexts. While this rural focus may limit the generalizability to urban or suburban settings, where healthcare access and lifestyle behaviors differ, the high global prevalences of obesity in rural areas ( 2 ) underscores the critical role of GPs in delivering obesity care in sparsely populated areas and broadens the applicability of GP-centered interventions there. The pragmatic design of our trial allowed for flexibility, such as the incorporation of unplanned social events and the use of a multi-centered approach, distributing patients among local physiotherapy providers, thereby reducing the administrative burden for rural GPs. Nonetheless, this flexibility introduced challenges: The management of sub-cohorts depended on the motivation and resources of individual GPs and physiotherapists, and the geographic distribution did not always align with patients’ personal or work schedules. Consequently, some patients missed parts of the program, complicating the assessment of specific intervention components on trial outcomes. The HAPpEN trial reported a dropout rate of 37.8%. While participants who remained engaged demonstrated high adherence and meaningful weight loss, the attrition rate indicates that the program’s full potential may not have been realized across the entire study population. This finding is consistent with previous research, showing that adherence to lifestyle-based obesity interventions typically declines over time due to the sustained effort and self-regulation required ( 38 ). High dropout rates, common in weight management programs, may introduce selection bias, as completes are more motivated or face fewer barriers ( 39 ). Contributing factors likely included competing personal and professional commitments, lack of immediate results, fluctuating motivations, and rural healthcare barriers. Nevertheless, the strong association between program participation and weight loss underscores the importance of strategies to improve retention and maximize program impact ( 40 ). Future research should focus on strategies to address barriers to sustained engagement, such as providing motivational support and continuous feedback ( 41 ), offering flexible participation options, and providing additional support for individuals at higher risk of dropout ( 42 , 43 ). These improvements could optimize the program’s effectiveness and increase long-term success in obesity prevention and management. In addition, a randomized controlled trial design would provide a more robust assessment of causality and strategies to optimize program retention and engagement, particularly for participants initially less motivated, should be explored to improve the intervention’s effectiveness. Finally, expanding the intervention to other underserved populations, such as urban areas with limited resources, could assess its broader applicability and identify potential areas for program refinement. CONCLUSION This trial demonstrated the effectiveness of a GP-centered, multifactorial intervention in promoting weight loss and improving cardiovascular and metabolic health in rural populations. Significant reductions in body weight, BMI, waist circumference, and HbA1c highlight its potential for obesity management and diabetes prevention. The positive correlation between engagement and weight loss underscores the importance of sustained participation. These findings emphasize the critical role of GPs in rural healthcare settings and support the broader applicability of GP-centered interventions in underserved areas. Abbreviations general practitioner (GP), body mass index (BMI), hemoglobin A1c (HbA1c), high- and low-density lipoprotein (HDL/LDL), C-reactive protein (CrP) Declarations Ethics approval: The HAPpEN trial has been positively approved by the ethics committee of the University of Bayreuth (Az. O 1305/1 – GB) stating: there are no ethical objections to carrying out the project. The trial is registered at the German Clinical Trial Register (DRKS00033916, March 20 th 2024 retrospectively registered). Consent to participate and for publication: All participants had given written informed consent (consent for publication included) to GPs prior to trial start. The medical data of patients are assigned a pseudonym, ensuring that the collected and transmitted data cannot be traced back to the individual person’s data. Availability of data and materials statement: The datasets generated and analyzed during the current trial are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: This work was supported by the Bavarian Federal Ministry of Health, Care and Prevention (G31i-G8000-2021/2630-23). Author Contributions: NvS, LK, TB, RH and MH initiated the HAPpEN project. The acquisition of funding for the trial was primarily led by NvS, RH and MH. NvS and MH were responsible for coordinating patients, GPs, and researchers. All authors contributed to the intervention's design and analysis of the intervention. NvS, CB, AW, AB and MH prepared tables, while MH was responsible for creating the figures. NvS, CB, AB, MM and MH drafted the initial manuscript, which was subsequently reviewed and revised by AW, LK, TB and RH. All authors read and approved the final manuscript. Acknowledgements: We acknowledge the Bavarian Federal Ministry of Health, Care and Prevention for funding this research and extend our gratitude to our patients and GPs for participating in this trial. We are also grateful to Susanne Tittlbach (Social and Health Science in Sport, University of Bayreuth, Bayreuth, Germany) for their support in the setup of the trial and valuable scientific discussions. Special thanks to Bria-Estella Johnson, Miriam Witthüser and Antonia Baldauf (Institute for Management in Medicine and Health Sciences, University of Bayreuth, Bayreuth, Germany) for assistance. References Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019; 15(5):288–98. Available from: URL: https://www.nature.com/articles/s41574-019-0176-8 NCD Risk Factor Collaboration. 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BMC Health Serv Res. 2022; 22(1):438. Available from: URL: https://bmchealthservres.biomedcentral.com/articles/ 10.1186/s12913-022-07829-2 Boehmer TK, Lovegreen SL, Haire-Joshu D, Brownson RC. What constitutes an obesogenic environment in rural communities? Am J Health Promot. 2006;20(6):411–21. Ely AC, Befort C, Banitt A, Gibson C, Sullivan D. A qualitative assessment of weight control among rural Kansas women. J Nutr Educ Behav. 2009;41(3):207–11. Kupila SKE, Joki A, Suojanen L-U, Pietiläinen KH. The Effectiveness of eHealth Interventions for Weight Loss and Weight Loss Maintenance in Adults with Overweight or Obesity: A Systematic Review of Systematic Reviews. Curr Obes Rep. 2023; 12(3):371–94. Available from: URL: https://link.springer.com/article/ 10.1007/s13679-023-00515-2 Chong SOK, Pedron S, Abdelmalak N, Laxy M, Stephan A-J. An umbrella review of effectiveness and efficacy trials for app-based health interventions. npj Digit. Med. 2023; 6(1):233. 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Available from: URL: https://onlinelibrary.wiley.com/doi/ 10.1111/obr.13542 König LM, Western MJ, Denton AH, Krukowski RA. Umbrella review of social inequality in digital interventions targeting dietary and physical activity behaviors. npj Digit. Med. 2025; 8(1):11. Available from: URL: https://www.nature.com/articles/s41746-024-01405-0 Wilson S, Tolley C, McArdle R, Slight R, Slight S. Who is most at risk of digital exclusion within healthcare? Int J Pharm Pract. 2024;32(Supplement1):i3–4. Fichtner UA, Armbruster C, Bischoff M, Maiwald P, Sehlbrede M, Tinsel I et al. Evaluation of an Interactive Web-Based Health Program for Weight Loss-A Randomized Controlled Trial. International Journal of Environmental Research and Public Health. 2022; 19(22):15157. Available from: URL: https://www.mdpi.com/1660-4601/19/22/15157 Kohl J, Brame J, Centner C, Wurst R, Fuchs R, Sehlbrede M et al. 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Analysis of the efficacy of an internet-based self-administered intervention (Living Better) to promote healthy habits in a population with obesity and hypertension: An exploratory randomized controlled trial. International journal of medical informatics. 2019; 124:13–23. Available from: URL: https://pubmed.ncbi.nlm.nih.gov/30784422/ Talay L, Vickers M, Ruiz L. Effectiveness of an Email-Based, Semaglutide-Supported Weight-Loss Service for People with Overweight and Obesity in Germany: A Real-World Retrospective Cohort Analysis. Obesities. 2024; 4(3):256–69. Available from: URL: https://www.mdpi.com/2673-4168/4/3/21 Wang L, Zhou B, Zhao Z, Yang L, Zhang M, Jiang Y et al. Body-mass index and obesity in urban and rural China: findings from consecutive nationally representative surveys during 2004-18. Lancet (London, England). 2021; 398(10294):53–63. Available from: URL: https://pubmed.ncbi.nlm.nih.gov/34217401/ Batsis JA, Gill LE, Masutani RK, Adachi-Mejia AM, Blunt HB, Bagley PJ et al. Weight Loss Interventions in Older Adults with Obesity: A Systematic Review of Randomized Controlled Trials Since 2005. Journal of the American Geriatrics Society. 2017; 65(2):257–68. Available from: URL: https://agsjournals.onlinelibrary.wiley.com/doi/ 10.1111/jgs.14514 Teixeira PJ, Carraça EV, Marques MM, Rutter H, Oppert J-M, Bourdeaudhuij I et al. de Successful behavior change in obesity interventions in adults: a systematic review of self-regulation mediators. BMC Med. 2015; 13(1):84. Available from: URL: https://bmcmedicine.biomedcentral.com/articles/ 10.1186/s12916-015-0323-6 Moroshko I, Brennan L, O'Brien P. Predictors of dropout in weight loss interventions: a systematic review of the literature. Obes Rev. 2011;12(11):912–34. Johnson F, Wardle J. The association between weight loss and engagement with a web-based food and exercise diary in a commercial weight loss programme: a retrospective analysis. Int J Behav Nutr Phys Act. 2011; 8(1):83. Available from: URL: https://ijbnpa.biomedcentral.com/articles/ 10.1186/1479-5868-8-83 Krukowski RA, Denton AH, König LM. Impact of feedback generation and presentation on self-monitoring behaviors, dietary intake, physical activity, and weight: a systematic review and meta-analysis. Int J Behav Nutr Phys Act. 2024; 21(1):3. Available from: URL: https://ijbnpa.biomedcentral.com/articles/ 10.1186/s12966-023-01555-6 Schmied EA, Madanat H, Chuang E, Moody J, Ibarra L, Cervantes G et al. Factors predicting parent engagement in a family-based childhood obesity prevention and control program. BMC Public Health. 2023; 23(1):457. Available from: URL: https://bmcpublichealth.biomedcentral.com/articles/ 10.1186/s12889-023-15359-7 Partridge SR, Redfern J. Strategies to Engage Adolescents in Digital Health Interventions for Obesity Prevention and Management. Healthcare. 2018; 6(3):70. Available from: URL: https://www.mdpi.com/2227-9032/6/3/70 Additional Declarations No competing interests reported. Supplementary Files 250413HAPpENHauptpaperSupplementsBMC.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 11 Sep, 2025 Reviews received at journal 11 Sep, 2025 Reviews received at journal 07 Sep, 2025 Reviewers agreed at journal 19 Aug, 2025 Reviewers agreed at journal 16 Aug, 2025 Reviewers invited by journal 13 May, 2025 Editor invited by journal 02 May, 2025 Editor assigned by journal 28 Apr, 2025 Submission checks completed at journal 28 Apr, 2025 First submitted to journal 27 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6540216","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":455959416,"identity":"04e875c0-6513-4d86-9f98-e26e651c8a30","order_by":0,"name":"Natascha Schau","email":"","orcid":"","institution":"Institute of General Practice, Friedrich-Alexander University Erlangen-Nuremberg","correspondingAuthor":false,"prefix":"","firstName":"Natascha","middleName":"","lastName":"Schau","suffix":""},{"id":455959417,"identity":"46a5f85c-9109-4e64-9660-33fbcb1597f2","order_by":1,"name":"Constanze Betz","email":"","orcid":"","institution":"Faculty of Life Sciences: Food, Nutrition, and Health, University of Bayreuth","correspondingAuthor":false,"prefix":"","firstName":"Constanze","middleName":"","lastName":"Betz","suffix":""},{"id":455959418,"identity":"0bf9d214-17b2-4cdf-aa5d-5d7a7afe4f80","order_by":2,"name":"Anna Weber","email":"","orcid":"","institution":"Institute for Medical Management and Health Sciences, Project office of the Medical Campus Upper Franconia, University of Bayreuth","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Weber","suffix":""},{"id":455959419,"identity":"ea908c2e-66aa-4662-a6d6-c0f3ffd974ad","order_by":3,"name":"Alisa Bader","email":"","orcid":"","institution":"Institute for Medical Management and Health Sciences, Project office of the Medical Campus Upper Franconia, University of Bayreuth","correspondingAuthor":false,"prefix":"","firstName":"Alisa","middleName":"","lastName":"Bader","suffix":""},{"id":455959420,"identity":"4c4acaa1-72aa-4b0e-8203-c16b15fc0d68","order_by":4,"name":"Laura M. König","email":"","orcid":"","institution":"Faculty of Psychology, University of Vienna","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"M.","lastName":"König","suffix":""},{"id":455959421,"identity":"1d56fa75-bff2-43e2-bef2-84167521ae9d","order_by":5,"name":"Tina Bartelmeß","email":"","orcid":"","institution":"Faculty of Life Sciences: Food, Nutrition, and Health, University of Bayreuth","correspondingAuthor":false,"prefix":"","firstName":"Tina","middleName":"","lastName":"Bartelmeß","suffix":""},{"id":455959430,"identity":"8ca21605-8393-4f4f-bf6c-90408d99a653","order_by":6,"name":"Mirna Al Masri","email":"","orcid":"","institution":"Faculty of Law, Business and Economics, University of Bayreuth","correspondingAuthor":false,"prefix":"","firstName":"Mirna","middleName":"Al","lastName":"Masri","suffix":""},{"id":455959431,"identity":"0313d291-2a65-407e-99c7-f4139c169519","order_by":7,"name":"Reiner Hofmann","email":"","orcid":"","institution":"Institute for Medical Management and Health Sciences, Project office of the Medical Campus Upper Franconia, University of Bayreuth","correspondingAuthor":false,"prefix":"","firstName":"Reiner","middleName":"","lastName":"Hofmann","suffix":""},{"id":455959432,"identity":"67748a45-93de-4faf-a325-6e942e319cb6","order_by":8,"name":"Marika Haderer","email":"data:image/png;base64,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","orcid":"","institution":"Faculty of Life Sciences: Food, Nutrition, and Health, University of Bayreuth","correspondingAuthor":true,"prefix":"","firstName":"Marika","middleName":"","lastName":"Haderer","suffix":""}],"badges":[],"createdAt":"2025-04-27 12:08:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6540216/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6540216/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82888319,"identity":"400ac207-767e-46c1-b768-db8bbbd094c3","added_by":"auto","created_at":"2025-05-16 12:01:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":115481,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart illustrating the trial timeline. Assessment points are at baseline (T0), 6 months (T6) and 12 months (T12). Reasons for participant dropout and corresponding numbers are detailed. Of 98 enrolled participants, 61 completed the trial, resulting in a dropout rate of 37.8%.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6540216/v1/6b4e5fc2e779e5fd2eda55c9.png"},{"id":82892159,"identity":"929e45a2-6a4f-4cd3-ba97-aa4e01812f92","added_by":"auto","created_at":"2025-05-16 12:17:41","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":194769,"visible":true,"origin":"","legend":"\u003cp\u003e12-month changes in BMI and HbA1c among HAPpEN intervention participants versus control group. (A) BMI of HAPpEN participants showed a significant reduction of -1.8 after 6 months (95% CI: [-2.48, -0.99], p\u0026lt; 0.001) and -1.7 after 12 months (95 % CI: [-2.48, -0.99], p\u0026lt; 0.001), while no significant change was observed in the control group. Red dashed lines indicate the thresholds for obesity classes (I: 30.0 – 34.9, II: 35.0 – 39.9, III: ≥ 40.0 kg/m²), showing a shift of the median towards obesity grade I in the intervention group after 12 months. (B) HbA1c levels significantly decreased within the HAPpEN intervention group by -0.3% after 6 months (95% CI: [-0.47, -0.09], p= 0.002) respectively -0.3% after 12 months (95% CI: [-0.49, –0.12], p\u0026lt; 0.001). The red dashed lines represent the references range for HbA1c levels (4.5 – 5.6), showing a shift of the majority of the participants of the intervention group towards normal range. One dot represents one patient. BMI: body mass index, HbA1C: hemoglobin A1C.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6540216/v1/d0e9a5f52ccad3ef9fabdab9.png"},{"id":82888321,"identity":"6d9c7ebd-7405-415c-b28c-fee26cb472f8","added_by":"auto","created_at":"2025-05-16 12:01:41","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":42400,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of 12-month program adherence and percentage weight change among HAPpEN participants. Using boxplots, self-reported time spent on the HAPpEN program is illustrated and categorized into four groups: \u0026lt; 3 h, 3 – 5 h, 5-7 h, and \u0026gt; 7 h per week. Red dashed lines indicate clinically relevant thresholds for weight loss of ≥ 5% and ≥ 10%. Spearman correlation showed a significant negative correlation between program adherence and weight loss [r\u003csub\u003es\u003c/sub\u003e=−0.45, p\u0026lt; 0.00).\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6540216/v1/aa8e6a7bf412cda08c09d692.jpg"},{"id":82893597,"identity":"ab403db7-b60f-4fdd-bb60-3ee2a1f20f0e","added_by":"auto","created_at":"2025-05-16 12:25:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2051025,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6540216/v1/06fe9eee-c820-447b-aa9d-e0fd61d5238d.pdf"},{"id":82890637,"identity":"161db682-d9d7-400a-9b89-06110caf660d","added_by":"auto","created_at":"2025-05-16 12:09:41","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":384662,"visible":true,"origin":"","legend":"","description":"","filename":"250413HAPpENHauptpaperSupplementsBMC.docx","url":"https://assets-eu.researchsquare.com/files/rs-6540216/v1/773155b9b66a37603a3228b2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"HAPpEN: A pragmatic general practitioner-centered obesity management trial in rural Germany integrating multimodal lifestyle interventions","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe global rise in obesity is a logical outcome of shifting dietary habits and lifestyle patterns as observed in recent decades. The literature highlights not only a significant increase in obesity prevalence but also notable disparities in its incidence across various ethnic groups, socioeconomic positions, and geographical regions (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Notably, the proportion of individuals affected by obesity is higher in rural areas compared to urban counterparts (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), a trend that is particularly pronounced in high-income and industrialized countries, where women, in particular, exhibit a greater prevalence of this inequality. Despite the general extended life expectancy in high-income countries, the rising prevalence of obesity in these regions is strongly associated with comorbidities such as type 2 diabetes, cardiovascular diseases, and cancer, reducing life expectancy by 5.6 to 10.3 years (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe reasons for higher obesity prevalence among rural residents remain insufficiently researched. However, weaker structures \u0026ndash; including gaps in medical care, preventive programs, and health-promoting infrastructures \u0026ndash; seem crucial (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Access to healthcare is often limited, with only a few or single facilities serving large districts, creating challenges for both patients and general practitioners (GPs). Patients face long travel distances and waiting times, while GPs must oversee extensive catchment areas, limiting the time available for individual consultations. Despite these challenges, GPs hold a pivotal position in the healthcare system as accessible and trusted primary care providers. They are uniquely positioned to consider the patient\u0026rsquo;s family and social context, as well as comorbidities, which can enhance patient trust and willingness to act on their advice. This was confirmed by Wrangler et al. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), demonstrating that patients view GPs as suitable partner in obesity management and, additionally, GP recommendations positively influences patient\u0026rsquo;s willingness to lose weight. However, significant deficiencies persist in obesity management, including delayed or incidental diagnosis, inconsistent counseling, infrequent establishment of weight reduction goals, limited referrals to support service, and occasional lack of sensitivity, underscoring the need for effective programs that integrate GP training. Additionally, practitioners report low confidence in the quality of obesity care provided. Schwenke et al.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) highlighted that doctors rate obesity management in primary care as below average, reinforcing the necessity for systemic improvements and comprehensive intervention strategies that address both GP and patient needs.\u003c/p\u003e \u003cp\u003eIn rural settings, where doctors benefit from a close familiarity with their patients but often face limited resources, low-threshold and flexible intervention strategies are particularly necessary. The HAPpEN trial explored innovative and scalable strategies for obesity management within a rural, GP-centered framework. By integrating regular GP-led consultations, educational workshops, digital self-monitoring, group-based physiotherapy, and community-based activities, the intervention aims to provide a modular, adaptable, and equitable approach to obesity care. Understanding weight loss dynamics and their broader health implications in rural primary care is critical. This pragmatic trial addresses the following objectives:\u003c/p\u003e \u003cp\u003e1. Effectiveness and Sustainability: Assessing the structured intervention\u0026rsquo;s impact on body weight and body mass index (BMI) compared to standard obesity treatment. 2. Metabolic and Inflammatory Markers: Evaluating cardiovascular parameters, glucose metabolism, lipid profiles, and systemic inflammation to determine the preventive potential of HAPpEN in reducing the risk of type 2 diabetes or cardiovascular diseases. 3. Physical Function and Medication Adjustment: Investigating changes in joint health, mobility, and medication health as indicators of physiotherapy- and physical activity-induced improvements. 4. Program Adherence and Weight Loss Contribution: Analyzing the relation between program engagement and individual weight loss outcomes.\u003c/p\u003e \u003cp\u003eBy systematically evaluating these factors, the study provides a comprehensive analysis of the intervention\u0026rsquo;s effectiveness and feasibility, offering critical insights for future implementation and policy development in rural obesity management.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eAim, design and setting of the study\u003c/h2\u003e \u003cp\u003eTo evaluate the effectiveness of a GP-centered, multifactorial intervention for obesity management in rural, sparsely populated settings, HAPpEN was conducted as a pragmatic trial across six rural primary care practices in Upper Franconia, Germany. Additionally, nine physiotherapists were involved in leading group-based exercise sessions. The enrollment period spanned from May to June 2023. Eligible participants were aged 18 to 65 years with a BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e. Comprehensive eligibility criteria are detailed in Supplementary Table\u0026nbsp;1. Participant recruitment was initiated by physicians during routine GP consultation and checkups, and was further supported by targeted outreach efforts, including informational posters, flyers and public announcements broadcast via local radio.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMultifactorial intervention\u003c/h3\u003e\n\u003cp\u003eThe HAPpEN program adheres to current clinical guidelines following the 5A model (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) and, emphasizing individualized care. Baseline assessments included (self-reported) medical history, physical exams, and laboratory testing to evaluate health status. GPs, serving as central coordinators, conducted follow-up evaluations at six (T6) and 12 (T12) months to monitor changes and potential risk factors. Primary outcomes comprised body weight, BMI, waist circumference, blood pressure, heart rate and metabolic parameters including hemoglobin A1c (HbA1c), fasting glucose, cholesterol, triglycerides, high- and low-density lipoproteins (HDL/LDL), C-reactive protein (CrP) and uric acid. Body weight and BMI were recorded monthly, while waist circumferences, blood pressure, heart rate and laboratory analysis were assessed at baseline and at follow-ups after six and 12 months, alongside physical exams of the heart, lungs, abdomen, joints, and spine to guide exercise recommendations and track progress. Ergometry was conducted following standardized protocols to assess physical fitness and exercise-induced blood pressure responses.\u003c/p\u003e \u003cp\u003eSecondary outcomes included assessments of quality of life, disease burden conceptualized as wellbeing, nutritional status, physical activity, health literacy, social interaction, and digital therapy support. The results of these assessments will be reported separately.\u003c/p\u003e \u003cp\u003eThroughout the trial, GPs developed individualized therapy plans focusing on nutrition, physical activity and behavioural modification while providing continuous motivational support. Participants received monthly in-office monitoring by their GP, supplemented by structured physiotherapy sessions and app-based self-monitoring. Education and social interaction were reinforced through digital learning modules and in-person activities, including cooking workshops and hiking events, fostering community engagement and sustainable health behaviour changes. The full trial setup, intervention and the description of the trial population is provided in the study protocol (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eControl patients\u003c/h3\u003e\n\u003cp\u003ePatients receiving current standard care (n\u0026thinsp;=\u0026thinsp;58) including a combination of nutritional therapy, exercise, and behavioural therapy (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) for obesity, administered by the same GPs within the same timeframe served as controls. In this context, body weight and BMI of these patients were analysed. However, these patients did not receive the structured education and monthly counselling on nutrition, physical activity or behaviour provided in the HAPpEN intervention program.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical calculations including descriptive statistics were performed using SPSS version 29. The comparison of the social anamnesis characteristics between the baseline population and the completers was employed either using a two-sample t-test or a Pearson Chi-squared test. Changes within the intervention group over time were tested using a one-way analysis of variance. For weight and BMI assessments, a two-way analysis of variance was conducted analyzing the effects between the intervention group and a control cohort over time. The post-hoc comparisons were performed using the Bonferroni test. For joint-related outcomes, Cochran\u0026rsquo;s Q test and Friedmann test were applied. Spearman correlation was conducted to examine the association between time spent on intervention and weight reduction (T0 - T12). Normality was assessed by graphical inspection or using the Shapiro-Wilk test and variance homogeneity was checked by using Levene\u0026rsquo;s test. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eArtificial intelligence statement\u003c/h3\u003e\n\u003cp\u003eIn the drafting of this manuscript, ChatGPT was employed to assist with spelling correction and language refinement.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eTrial and population characteristics\u003c/h2\u003e \u003cp\u003eBetween May and June 2023, 98 eligible participants representing the baseline cohort (T0) were enrolled in the trial (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). They were all German, with a mean age of 46.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8 years. The majority of patients were female (74.1%, see Supplementary Table\u0026nbsp;2) and the BMI was 40.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1 kg/m\u0026sup2;, with 48.5% classified as having grade III obesity (BMI\u0026thinsp;\u0026ge;\u0026thinsp;40 kg/m\u0026sup2;) (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). A total of 61 patients (62.2%) completed the 12 months follow-up (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Sociodemographic factors or previous years spent on weight reduction were unrelated to dropout, as a comparison of these characteristics between the dropouts and final population showed no significant differences (see Supplementary Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBased on the clinical record of the baseline population, the prevalence of hypertension was notably high at 59.6% (see Supplementary Table\u0026nbsp;3). Dyslipidemias and type 2 diabetes were also prevalent, affecting 21.3% and 19.1% of participants, respectively, while latent diabetes was reported in 12.8%. Obesity-related conditions were common, including venous insufficiency (25.5%), obstructive sleep apnea (3.2%), and lipedema (2.1%). Additional diagnoses included hypothyroidism (8.5%), asymptomatic hyperuricemia (11.7%), gastroesophageal reflux disease (10.6%) and depressive episodes (11.7%). Musculoskeletal disorders were also frequent, with gonarthrosis (12.8%), coxarthrosis (7.4%), degenerative spinal diseases (10.6%), and chronic back pain, including radiculopathy and lumbago (17.0%). These findings highlight the substantial burden of metabolic, cardiovascular, psychiatric, and musculoskeletal comorbidities within this cohort, emphasizing the necessity for comprehensive and multidisciplinary management strategies to address these interconnected health challenges. Notably, participants\u0026rsquo; self-assessment of their health status, as measured by questionnaire (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), showed only minor deviations from the documented clinical diagnoses, indicating a accurate perception of their own health conditions.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eClinical outcome\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eComparisons to control patients: Changes in body weight and BMI\u003c/h2\u003e \u003cp\u003eIn the completers analysis, the intervention group exhibited a higher mean body weight (+\u0026thinsp;6.8 kg, 95% CI: [-1.07, 14.62], p\u0026thinsp;=\u0026thinsp;0.090) and BMI (+\u0026thinsp;2.3 kg/m\u003csup\u003e2\u003c/sup\u003e, 95% CI: [0.08; 4.55], p\u0026thinsp;=\u0026thinsp;0.042) at baseline compared to the control group, with a greater proportion of participants classified as having obesity grade III (+\u0026thinsp;14.9%) and grade II (+\u0026thinsp;5.4%) (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA two-way analysis of variances yielded a significant time x group interaction effect (F(1.77, 206.47)\u0026thinsp;=\u0026thinsp;8.52, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, ηp\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.07), indicating greater weight reduction in the intervention group compared to controls (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Over the course of the trial, the intervention group experienced a significant reduction in body weight, with a mean loss of -5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5 kg from T0 to T6 (95% CI: [-7.33, -3.40], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and \u0026minus;\u0026thinsp;5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7 kg from T0 to T12 (95% CI: [-7.24, -2.83], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Weight loss was most pronounced in the first six months, followed by weight maintenance between T6 and T12 (+\u0026thinsp;0.3 kg, 95% CI: [-1.26, 1.91], p\u0026thinsp;=\u0026thinsp;1.000), despite seasonal challenges such as Christmas and New Year, during which a temporary weight increase was observed (see Supplementary Fig.\u0026nbsp;1). By T6, 42.6% of participants in the intervention group achieved\u0026thinsp;\u0026ge;\u0026thinsp;5% and 9.8% achieved\u0026thinsp;\u0026ge;\u0026thinsp;10% weight loss, compared to 16.4% and 19.7% by T12 (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In contrast, no significant weight changes were observed in the control group, with an average weight reduction of -1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1 kg from T0 to T6 (95% CI: [-3.23, 0.80, p\u0026thinsp;=\u0026thinsp;0.434) and \u0026minus;\u0026thinsp;1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4 kg from T0 to T12 (95% CI: [-3.29, 1.24, p\u0026thinsp;=\u0026thinsp;0.820).\u003c/p\u003e \u003cp\u003eSimilarly, a significant time x group interaction effect was noted for BMI (F(1.77, 207.17)\u0026thinsp;=\u0026thinsp;8.73, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, ηp\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.07), confirming a more pronounced BMI reduction in the intervention group. BMI in the HAPpEN group decreased significantly by -1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2 kg/m\u003csup\u003e2\u003c/sup\u003e from T0 to T6 (95% CI: [-2.48, -0.99], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and by -1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6 kg/m\u003csup\u003e2\u003c/sup\u003e from T0 to T12 (95% CI: [-2.48, -0.99], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with minimal changes between T6 and T12. By T12, the intervention group showed a shift towards lower BMI classes, with an increase in participants classified as overweight (+\u0026thinsp;6.6%) and reductions in obesity grade II (-6.5%) and grade III (-3.3%) (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eChanges over time in HAPpEN patients: Waist circumference, blood pressure, cardiovascular fitness and blood parameters\u003c/h2\u003e \u003cp\u003eIn alignment with weight loss, waist circumference significantly decreased over time among participants enrolled in the HAPpEN intervention group. The mean waist circumference declined by -8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8 cm from T0 to T6 (95% CI: [-12.42, -4.40], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and further by -11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1 from T0 to T12 (95% CI: [-15.57, -7.34], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; F(1.35, 59.21)\u0026thinsp;=\u0026thinsp;35.59, ηp\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.45) (see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Additionally, systolic blood pressure showed significant reductions by T12 (systolic: F(1.77, 86.70)\u0026thinsp;=\u0026thinsp;6.15, p\u0026thinsp;=\u0026thinsp;0.04, ηp\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.11).\u003c/p\u003e \u003cp\u003eDuring physical exertion, significant reductions in systolic diastolic blood pressure were observed from T0 to T6 at 75 W(systolic: F(2, 78)\u0026thinsp;=\u0026thinsp;7.65, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, ηp\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.16; diastolic: F(2, 78)\u0026thinsp;=\u0026thinsp;7.09, p\u0026thinsp;=\u0026thinsp;0.01, ηp\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.15) and at 125 W (systolic: F(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e)\u0026thinsp;=\u0026thinsp;3.94, p\u0026thinsp;=\u0026thinsp;0.028, ηp\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.17; diastolic: F(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e)\u0026thinsp;=\u0026thinsp;3.80, p\u0026thinsp;=\u0026thinsp;0.031, ηp\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.17). Additionally, the mean maximal wattage achieved during ergometry assessments increased by +\u0026thinsp;6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;21.2 W (95% CI: [-1.31, 14.80], p\u0026thinsp;=\u0026thinsp;0.129) at T6 (see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), reflecting improved cardiovascular fitness. Conversely, heart rate did not exhibit statistically significant changes, nor did glucose, uric acid, triglycerides, cholesterol, HDL- and LDL-cholesterol over the trial period (see Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, percental HbA1c level decreased significantly by -0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6% both from T0 to T6 and T0 to T12 (T6: 95% CI: [-0.47, -0.09], T12: 95% CI: [-0.49, -0.12], F(1.19, 67.91)\u0026thinsp;=\u0026thinsp;13.39, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, ηp\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.19) (see Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Similarly, absolute HbA1c decreased by -3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2 mmol/mol at T12 (95% CI: [-5.33, -1.30], F(1.19, 68.00)\u0026thinsp;=\u0026thinsp;13.55, p\u0026thinsp;\u0026lt;\u0026thinsp;0,001, ηp\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.19) (see Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The significant reduction in HbA1c levels, alongside decreases in weight, BMI, and blood pressure, indicates that HAPpEN contributed to improved glycemic control, lowering the risk of developing type 2 diabetes. In line, the improvement in ergometry parameters enhanced cardiovascular fitness, further supporting diabetes prevention.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eComorbidities and Medication Use\u003c/h2\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, the knee and shoulder joints emerged as the most frequently affected sites of pain among individuals with obesity. The hips also demonstrated a comparatively high prevalence of pain, while pain in the fingers, wrists, ankles, toe joints and elbows was reported less frequently. The proportion of participants reporting overall physical complaints was pretty high, but significantly decreased over trial time, from 81.6% at baseline (T0) to 65.3% at T12 (Q(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u0026thinsp;=\u0026thinsp;8.59, p\u0026thinsp;=\u0026thinsp;0.014). In contrast, the prevalence of joint complaints over the past 12 months as well as in the last 24 hours remained stable. In addition, joint health metrics remained unchanged and no significant changes in the medication regimes were seen for the participants either (see Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). All medication categories showed stable usage patterns during the trial, with minimal fluctuations. Thus, the proportion of participants on antihypertensives as the most prevalent medication remained 60.3\u0026ndash;63.8%, while diuretics and statins as the second most common drugs were consistent at 31.0\u0026ndash;32.8% and 19.0%. Given the significant reductions in body weight, BMI, waist circumference, blood pressure and HbA1C observed, the lack of change in joint complaints and medication use suggests that improvements in metabolic health may not immediately translate into measurable reduction in musculoskeletal burden.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eEngagement with HAPpEN program and association with weight loss\u003c/h2\u003e \u003cp\u003eA Spearman correlation was conducted to assess the relationship between participation time in HAPpEN as an indicator for program engagement and individual weight loss in percent from T0 to T12. The analysis showed a significant negative correlation [r\u003csub\u003es\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.45, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, n\u0026thinsp;=\u0026thinsp;51) indicating that higher weekly participation in the HAPpEN program was associated with greater weight loss over the trial period (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). This finding suggests that increased engagement in the intervention contributes to enhanced weight reduction outcomes, supporting the effectiveness of consistent participation in structured health programs.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical parameters of participants in HAPpEN intervention group and control cohort.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eparameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003egroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT0\u003c/p\u003e \u003cp\u003e[95% CI] or (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT6\u003c/p\u003e \u003cp\u003e[95% CI] or (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT12\u003c/p\u003e \u003cp\u003e[95% CI] or (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eT0 to T6\u003c/p\u003e \u003cp\u003e[95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eT6 to T12\u003c/p\u003e \u003cp\u003e[95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eT0 to T12\u003c/p\u003e \u003cp\u003e[95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003etime effect\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003etime x group effect\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWeight (kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControls\u003c/p\u003e \u003cp\u003eHAPpEN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111.8\u0026thinsp;\u0026plusmn;\u0026thinsp;20.2 [106.18, 117.41]\u003c/p\u003e \u003cp\u003e118.6\u0026thinsp;\u0026plusmn;\u0026thinsp;22.8 [113.09, 124.05]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e110.6\u0026thinsp;\u0026plusmn;\u0026thinsp;19.3 [105.06, 116.10]\u003c/p\u003e \u003cp\u003e113.0\u0026thinsp;\u0026plusmn;\u0026thinsp;22.9 [107.82, 118.59]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e110.8\u0026thinsp;\u0026plusmn;\u0026thinsp;20.1 [105.03, 116.51]\u003c/p\u003e \u003cp\u003e113.5\u0026thinsp;\u0026plusmn;\u0026thinsp;23.8 [107.94, 119.13]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1 [\u0026ndash; 3.23, 0.80]\u003c/p\u003e \u003cp\u003e-5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5 [-7.33, -3.40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2 [-1.43, 1.82]\u003c/p\u003e \u003cp\u003e0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0 [-1.26, 1.91]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4 [-3.29, 1.24]\u003c/p\u003e \u003cp\u003e-5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7 [-7.24, -2.83]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWeight loss (%)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e5%/ 10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControls\u003c/p\u003e \u003cp\u003eHAPpEN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.8 (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)/ 1,7 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e42.6 (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)/ 9.8 (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13,8 (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)/ 3,4 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e16.4 (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)/ 19.7 (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI (kg/m\u0026sup2;)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControls\u003c/p\u003e \u003cp\u003eHAPpEN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8 [36.39, 39.59]\u003c/p\u003e \u003cp\u003e40.3\u0026nbsp;\u0026plusmn; 6.5 [38.75, 41.86]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4 [36.00, 39.16]\u003c/p\u003e \u003cp\u003e38.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7 [36.94, 40.01]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7 [36.00, 39.28]\u003c/p\u003e \u003cp\u003e38.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8 [36.97, 40.17]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 [-1.10, -0.29]\u003c/p\u003e \u003cp\u003e-1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2 [-2.48, -0.994]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 [-0.49, 0.61]\u003c/p\u003e \u003cp\u003e0.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 [-0.44, 0.63]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 [-1.12, 0.41]\u003c/p\u003e \u003cp\u003e-1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6 [-2.48, -0.99]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI classes (%)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eOverweight\u003c/p\u003e \u003cp\u003eObesity grade I\u003c/p\u003e \u003cp\u003eObesity grade II\u003c/p\u003e \u003cp\u003eObesity grade III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControls\u003c/p\u003e \u003cp\u003eHAPpEN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003cp\u003e44.8 (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e24.1 (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e31.0 (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003cp\u003e24.6 (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e29.5 (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e45.9 (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003cp\u003e43.1 (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e22.4 (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e34.5 (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e6.6 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e29.5 (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e26.2 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e37.7 (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.2 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e37.9 (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e24.1 (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e32.8 (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e6.6 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e27.9 (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e23.0 (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e42.6 (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eData are shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation at baseline (T0), after six (T6) and twelve months (T12) including statistical analysis performed using a two-way analysis of variances across time points (T0- T12). The HAPpEN Intervention group is represented by 61 participants, the control cohort by 58 participants. BMI: body mass index\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical parameters of participants in HAPpEN intervention group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eparameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT0\u003c/p\u003e \u003cp\u003e[95% CI] or (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT6\u003c/p\u003e \u003cp\u003e[95% CI] or (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT12\u003c/p\u003e \u003cp\u003e[95% CI] or (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT0 to T6\u003c/p\u003e \u003cp\u003e[95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eT6 to T12 [95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eT0 to T12\u003c/p\u003e \u003cp\u003e[95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003etime effect\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbdominal circumference (cm\u003c/b\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e123.7\u0026thinsp;\u0026plusmn;\u0026thinsp;14.3 [119.43, 128.01]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e115.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2 [111.05, 119.57]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e112.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.7 [107.84, 116.69]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8 [-12.42, -4.40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2 [-4.97, -1.12]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1 [-15.57, -7.34]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBP (mmHg)\u003c/b\u003e\u003c/p\u003e \u003cp\u003esystolic\u003c/p\u003e \u003cp\u003ediastolic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0 [132.13, 140.07]\u003c/p\u003e \u003cp\u003e85.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9 [82.67, 87.77]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.6 [125.90, 134.78]\u003c/p\u003e \u003cp\u003e83.6\u0026thinsp;\u0026plusmn;\u0026thinsp;11.4 [80.36, 86.84]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e127.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8 [124.21, 131.47]\u003c/p\u003e \u003cp\u003e80.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4 [78.20\u0026ndash;83.52]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;19.6 [-12.62, 1.10]\u003c/p\u003e \u003cp\u003e-1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3 [-6.28, 3.04]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;17.1 [-8.49, 3.49]\u003c/p\u003e \u003cp\u003e-2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9 [-7.61, 2.13]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-8.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2 [-13.22, -3.30]\u003c/p\u003e \u003cp\u003e-4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6 [-7.73, -0.99]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eErgometry Maximum W\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139.8\u0026thinsp;\u0026plusmn;\u0026thinsp;30.1 [130.51, 149.03]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e146.5\u0026thinsp;\u0026plusmn;\u0026thinsp;35.2 [135.69, 157.34]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e144.2\u0026thinsp;\u0026plusmn;\u0026thinsp;30.3 [134.86, 153.51]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;21.2 [-1.31, 14.80]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;23.7 [-11.32, 6.67]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;22.7 [-4.22, 13.07]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eErgometry classification\u003c/b\u003e\u0026nbsp;%\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;125 watts\u003c/p\u003e \u003cp\u003e\u0026ge;\u0026thinsp;125 watts\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.8 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e84.2 (48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.3 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e85.7 (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.0 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e81.0 (47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBP (mmHg) \u0026ndash; 75 W\u003c/b\u003e\u003c/p\u003e \u003cp\u003esystolic\u003c/p\u003e \u003cp\u003ediastolic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e162.8\u0026thinsp;\u0026plusmn;\u0026thinsp;20.9 [156.07, 169.44]\u003c/p\u003e \u003cp\u003e92.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.6 [88.02, 96.08]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e151.0\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8 [146.87, 155.08]\u003c/p\u003e \u003cp\u003e84.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9 [81.69, 87.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e155.8\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8 [150.07, 161.44]\u003c/p\u003e \u003cp\u003e87.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7 [83.45, 91.55]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-11.8\u0026thinsp;\u0026plusmn;\u0026thinsp;20.0 [-19.70, -3.85]\u003c/p\u003e \u003cp\u003e-7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9[-13.04, -2.01]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;17.1 [-1.99, 11.54]\u003c/p\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2 [-1.08, 7.03]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;20.2 [-14.98, 0.98]\u003c/p\u003e \u003cp\u003e-4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;13.7 [-9.96, 0.86]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBP (mmHg) \u0026ndash; 100 W\u003c/b\u003e\u003c/p\u003e \u003cp\u003esystolic\u003c/p\u003e \u003cp\u003ediastolic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e172.5\u0026thinsp;\u0026plusmn;\u0026thinsp;22.7 [163.70, 181.31]\u003c/p\u003e \u003cp\u003e94.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0 [90.58, 98.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e164.0\u0026thinsp;\u0026plusmn;\u0026thinsp;16.2 [157.71, 170.29]\u003c/p\u003e \u003cp\u003e89.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9 [85.41, 93.85]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e166.8\u0026thinsp;\u0026plusmn;\u0026thinsp;27.6 [156.06, 177.44]\u003c/p\u003e \u003cp\u003e90.4\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8 [83.54, 97.32]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-8.5\u0026thinsp;\u0026plusmn;\u0026thinsp;22.0 [-19.09, 2.09]\u003c/p\u003e \u003cp\u003e-4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2 [-9.27, -0.41]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;25.2 [-9.43, 14.93]\u003c/p\u003e \u003cp\u003e0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.8 [-6.36, 7.96]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;27.3 [-18.94, 7.44]\u003c/p\u003e \u003cp\u003e-4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6 [-11.07, 2.99]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.194\u003c/p\u003e \u003cp\u003e0.135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBP (mmHg) \u0026ndash; 125 W\u003c/b\u003e\u003c/p\u003e \u003cp\u003esystolic\u003c/p\u003e \u003cp\u003ediastolic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e187.8\u0026thinsp;\u0026plusmn;\u0026thinsp;18.9 [178.91, 196.59]\u003c/p\u003e \u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5 [94.17, 105.83]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e173.8\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5 [165.58, 181.92]\u003c/p\u003e \u003cp\u003e92.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.4 [88.59, 96.41]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e184.5\u0026thinsp;\u0026plusmn;\u0026thinsp;22.9 [173.77, 195.23]\u003c/p\u003e \u003cp\u003e96.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.1 [88.94, 104.06]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-14.0\u0026thinsp;\u0026plusmn;\u0026thinsp;24.6 [-28.46, 0.46]\u003c/p\u003e \u003cp\u003e-7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0 [-14.53, -0.47]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.8\u0026thinsp;\u0026plusmn;\u0026thinsp;24.5 [-3.64, 25.14]\u003c/p\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1 [-2.50, 10.50]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;20.7 [-15.38, 8.89]\u003c/p\u003e \u003cp\u003e-3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.4 [-11.36, 4.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.031\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBP (mmHg) \u0026ndash; 150 W\u003c/b\u003e\u003c/p\u003e \u003cp\u003esystolic\u003c/p\u003e \u003cp\u003ediastolic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e192.1\u0026thinsp;\u0026plusmn;\u0026thinsp;25.9 [175.63, 208.53]\u003c/p\u003e \u003cp\u003e96.3\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1 [88.57, 103.93]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e177.9\u0026thinsp;\u0026plusmn;\u0026thinsp;18.3 [166.31, 189.53]\u003c/p\u003e \u003cp\u003e90.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8 [84.42, 95.59]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e185.8\u0026thinsp;\u0026plusmn;\u0026thinsp;22.3 [171.64, 200.03]\u003c/p\u003e \u003cp\u003e87.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5 [83.93, 90.90]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-14.2\u0026thinsp;\u0026plusmn;\u0026thinsp;19.6 [-30.15, 1.82]\u003c/p\u003e \u003cp\u003e-6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5 [-14.78, 2.28]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;19.7 [-8.13, 23.96]\u003c/p\u003e \u003cp\u003e-2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4 [-12.65, 7.48]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;22.5 [-24.55, 12.05]\u003c/p\u003e \u003cp\u003e-8.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.5 [-20.60, 2.94]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.080\u003c/p\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHeart rate (beats/min)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0 [75.63, 82.58]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2 [74.78, 80.72]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9 [72.70, 79.01]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;14.3 [-6.48, 3.77]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5 [-5.65, 1.86]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2 [-8.33, 1.83]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eData are shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation at baseline (T0), after six (T6) and twelve months (T12) including statistical analysis performed using a one-way analysis of variances across time points (T0- T12). BP: blood pressure, W: wattage\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory parameters of participants in the HAPpEN intervention group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eparameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT0 [95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT6 [95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT12 [95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eT0 to T6\u003c/p\u003e \u003cp\u003e[95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eT6 to T12\u003c/p\u003e \u003cp\u003e[95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eT0 to T12 [95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003etime effect\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlucose (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\u0026ndash;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e102.2\u0026thinsp;\u0026plusmn;\u0026thinsp;23.6 [96.11, 108.22]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e97.0\u0026thinsp;\u0026plusmn;\u0026thinsp;19.6 [92.01, 102.02]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100.7\u0026thinsp;\u0026plusmn;\u0026thinsp;19.6 [95.65, 105.67]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e-5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;18.8 [-11.07, 0.78]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;14.5 [-0.94, 8.22]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;17.1 [-6.90, 3.88]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHbA1C\u003c/b\u003e (\u003cb\u003e%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5\u0026ndash;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9 [5.71, 6.17]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 [5.53, 5.80]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 [5.51, 5.76]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e-0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6 [-0.47, -0.09]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e-0.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21 [-0.10, 0.04]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6 [-0.49, -0.12]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHbA1C (mmol/mol)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.0\u0026ndash;38.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e41.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5 [38.81, 43.83]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e38.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7 [36.88, 39.87]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1 [36.7, 39.35]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e-2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4 [-5.02, -0.87]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e-0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2 [-1.10, 0.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2 [-5.33, -1.30]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUric Acid (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1 [4.69, 10.32]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 [5.46, 6.20]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 [5.47, 6.20]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e-1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.6 [-5.02, 1.76]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e0.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90 [-0.28, 0.29]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.6 [-4.99, -1.74]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.241\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUric Acid (mg/dl) - female\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.4\u0026ndash;5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.7 [3.32, 12.23]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2[5.03, 5.83]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 [5.01, 5.93]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e-2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1 [-7.62, 2.93]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 [-0.27, 0.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1 [-7.56, 2.95]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUric Acid (mg/dl) - male\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.4-7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6 [6.23, 7.87]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 [5.98, 7.44]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1[6.11, 7.24]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e-0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 [-1.51, 0.84]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e0.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12 [-0.69, 0.76]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 [-1.25, 0.51]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.519\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTriglycerides (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e154.4\u0026thinsp;\u0026plusmn;\u0026thinsp;85.5 [132.31, 176.49]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e140.1\u0026thinsp;\u0026plusmn;\u0026thinsp;76.0 [121.26, 160.51]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e150.1\u0026thinsp;\u0026plusmn;\u0026thinsp;100.7 [124.10, 176.10]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e-13.5\u0026thinsp;\u0026plusmn;\u0026thinsp;55.9 [-31.29, 4.26]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;71.5 [-13.53, 31.97]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;70.3 [-26.68, -18.08]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCholesterol (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e196.3\u0026thinsp;\u0026plusmn;\u0026thinsp;42.3 [85.39, 207.24]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e196.5\u0026thinsp;\u0026plusmn;\u0026thinsp;42.8 [185.42, 207.54]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e198.3\u0026thinsp;\u0026plusmn;\u0026thinsp;48.7 [185.67, 210.83]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;19.5 [-6.02, 6.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;27.6 [-7.02, 10.55]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;28.5[-7.14, 11.01]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHDL Cholesterol (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e52.0\u0026thinsp;\u0026plusmn;\u0026thinsp;16.2 [47.78, 56.13]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e53.0\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9 [49.39, 56.58]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52.4\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8 [48.32, 56.48]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0 [-1.20, 3.27]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e-0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1 [-2.84, 1.68]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1 [-3.02, 2.12]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.559\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLDL Cholesterol (mg/dl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e116.8\u0026thinsp;\u0026plusmn;\u0026thinsp;34.6 [107.82, 125.72]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e118.5\u0026thinsp;\u0026plusmn;\u0026thinsp;36.0 [109.14, 127.76]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e118.1\u0026thinsp;\u0026plusmn;\u0026thinsp;40.1 [107.77, 128.46]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;17.1 [-3.75, 7.12]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e-0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;24.2 [-8.02, 7.36]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;26.3 [-7.01, 9.71]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCrP (mg/l)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5 [4.39, 7.23]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0 [4.05, 6.62]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8 [3.37, 5.35]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e-0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7 [-1.66, 0.71]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e-1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7 [-2.14, 0.20]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4 [-2.84, -0.06]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eData are shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation at baseline (T0), after six (T6) and twelve months (T12), including statistical analysis performed using a one-way analysis of variances across time points (T0- T12). HbA1C: hemoglobin A1C, HDL: high-density lipoprotein, LDL: low-density lipoprotein, CrP: C-reactive protein\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescriptive analysis of self-reported joint complaints in the HAPpEN intervention group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT12\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCochran-Q\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eChi-squared test\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003edf\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOverall physical complaints\u003c/b\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e8.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eJoint complaints last 12 months\u003c/b\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eJoint complaints last 24 hours\u003c/b\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.522\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003ePain in the last 24 hours\u003c/b\u003e (%)\u003c/p\u003e \u003cp\u003eLight/Moderate/Severe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eShoulder\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft side: 14.5/ 7.3/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 16.4/ 5.5/ 1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLeft side: 10.9/ 7.3/ 7.3\u003c/p\u003e \u003cp\u003eRight side: 14.5/ 7.3/ 3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLeft side: 20.0/ 12.7/ 3.6\u003c/p\u003e \u003cp\u003eRight side: 20.0/10.9/ 1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.122\u003c/p\u003e \u003cp\u003e0.460\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.21\u003c/p\u003e \u003cp\u003e1.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eElbow\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft side: 1.8/1.8/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 5.5/ 1.8/ 1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLeft side: 10.9/3.6/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 10.9/ 1.8/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLeft side: 9.1/ 1.8/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 9.1/ 1.8/ 1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.116\u003c/p\u003e \u003cp\u003e0.544\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.31\u003c/p\u003e \u003cp\u003e1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eWrist\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft side: 5.5/ 3.6/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 3.6/ 7.3/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLeft side: 14.6/ 3.6/ 1.8\u003c/p\u003e \u003cp\u003eRight side: 14.5/ 5.5/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLeft side: 16.4/ 3.6/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 14.5/ 3.6/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003cp\u003e0.414\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.31\u003c/p\u003e \u003cp\u003e1.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFinger joint\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft side: 10.9/ 5.5/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 9.1/ 7.3/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLeft side: 10.9/ 1.8/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 10.9/ 1.8/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLeft side: 12.7/ 3.6/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 12.7/ 7.3/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.670\u003c/p\u003e \u003cp\u003e0.205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003cp\u003e3.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHip\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft side: 7.3/ 7.3/ 3.6\u003c/p\u003e \u003cp\u003eRight side: 10.9/ 3.6/ 7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLeft side: 7.3/ 14.5/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 5.5/ 10.9/ 3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLeft side: 12.7/ 9.1/ 1.8\u003c/p\u003e \u003cp\u003eRight side: 9.1/ 10.9/ 1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.581\u003c/p\u003e \u003cp\u003e0.880\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.09\u003c/p\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eKnee\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft side: 14.5/ 12.7/ 1.8\u003c/p\u003e \u003cp\u003eRight side: 18.2/ 12.7/ 1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLeft side: 9.1/ 18.2/ 1.8\u003c/p\u003e \u003cp\u003eRight side: 10.9/ 14.5/ 1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLeft side: 3.6/ 20.0/ 3.6\u003c/p\u003e \u003cp\u003eRight side: 5.5/ 20.0/ 3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.781\u003c/p\u003e \u003cp\u003e0.694\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAnkle\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft side: 9.1/ 7.3/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 7.3/9.1/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLeft side: 10.9/ 10.9/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 9.1/ 12.7/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLeft side: 9.1/ 7.3/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 7.3/ 7.3/ 1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.469\u003c/p\u003e \u003cp\u003e0.510\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.51\u003c/p\u003e \u003cp\u003e1.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eToe joint\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft side: 3.6/ 5.5/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 3.6/ 3.6/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLeft side: 10.9/ 1.8/ 1.8\u003c/p\u003e \u003cp\u003eRight side: 12.7/ 1.8/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLeft side: 7.3/ 5.5/ 0.0\u003c/p\u003e \u003cp\u003eRight side: 7.3/ 5.5/ 0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.674\u003c/p\u003e \u003cp\u003e0.307\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003cp\u003e2.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eData are shown as completers analysis at baseline (T0), after six (T6) and twelve months (T12), including statistical analysis performed using either Cochran-Q or Friedmann test. While significant improvements in general physical complaints were observed during the trial, no significant changes were shown in joint complaints.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescriptive and statistical analysis of medications from participants in the HAPpEN intervention trial.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMedication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eFinal Population (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCochran-Q\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003edf\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntihypertensives\u003c/b\u003e (Ramipril, Amlodipine, Bisoprolol, Valsartan, Enalapril)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.641\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"14\" rowspan=\"15\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiuretics\u003c/b\u003e (Furosemide, Piretanide, Torasemide, Hydrochlorothiazide)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.846\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntidiabetic/Biguanides\u003c/b\u003e (Metformin)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.717\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDPP-IV Inhibitors\u003c/b\u003e (Linagliptin, Saxagliptin, Sitagliptin, Vildagliptin)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGLP Analogues\u003c/b\u003e (Dulaglutid, Exenatid, Liraglutid)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSGLT2 Inhibitors\u003c/b\u003e (Empagliflozin, Dapagliflozin)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.717\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePPI\u003c/b\u003e (Omeprazole, Pantoprazole, Esomeprazole)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStatins\u003c/b\u003e (Atorvastatin, Rosuvastatin, Simvastatin)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCholesterol Absorption Inhibitors\u003c/b\u003e (Ezetimibe)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCholesterol Synthesis Inhibitors\u003c/b\u003e (Bempedoic Acid)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBile Acid Sequestrants\u003c/b\u003e (Cholestyramine)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnalgetics\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(Ibuprofen, Etoricoxib, Celecoxib, Metamizole, Diclofenac)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.513\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnticonvulsants\u003c/b\u003e (Pregabalin)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePsychotropic Drugs\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTricyclic Antidepressants (Amitriptyline, Clomi-pramine, Desipramine, Nortriptyline)\u003c/p\u003e \u003cp\u003eSelective Serotonin Reuptake Inhibitors (Citalopram, Sertraline, Fluoxetine)\u003c/p\u003e \u003cp\u003eSerotonin-Norepinephrine Reuptake Inhibitors (Venlafaxine, Duloxetine)\u003c/p\u003e \u003cp\u003eNorepinephrine-Dopamine Reuptake Inhibitor (Bupropion)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.264\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntipsychotics/Neuroleptics\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(Olanzapine, Clozapine, Quetiapine, Ziprasidone, Aripiprazole)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e Information on medication was obtained from the patient\u0026rsquo;s medication plans (n\u0026thinsp;=\u0026thinsp;58). Anticonvulsants (Valproate, Carbamazepine, Lamotrigine, Topiramate), psychotropic drugs (Lithium), and steroids were not consumed by any of the participants and therefore not included in the table. For statistical analysis Cochran\u0026rsquo;s Q test was applied.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe present trial examined the impact of a GP-centered, multifactorial intervention focusing on exercise and nutrition on weight loss and metabolic health markers in rural populations, where obesity prevalence has been notably high (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Our findings show significant reductions in body weight, BMI, waist circumference and improved HbA1c levels from enrollment to trial completion.\u003c/p\u003e \u003cp\u003eThe most significant weight loss was observed between T0 and T6, aligning with evidence that the initial phase of weight reduction is typically the most pronounced (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Thereafter, weight maintenance became predominant, despite external challenges such as the holiday season, during which a temporary weight increase was observed but subsequently reversed, indicating adherence resilience (\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In contrast but consistent with literature (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), the control group undergoing standard treatment did not exhibit significant weight changes throughout the study period, underscoring the efficacy of the intervention program. With the significant reductions in waist circumference and HbA1c next to body weight and BMI, the intervention's potential to lower the risk of type 2 diabetes and in glycemic improvements is highlighted, too (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Improvements in blood pressure and ergometry parameters further suggest benefits for long-term cardiovascular health. These findings align with previous research and confirm the effectiveness of primary care interventions in managing obesity and related comorbidities in rural populations (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe HAPpEN trial effectively addressed rural healthcare challenges by integrating structured follow-ups with already familiarized GPs, local grouped physiotherapy, and digital self-monitoring, demonstrating its viability as an obesity management model in underserved areas (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Moreover, the trial enabled dynamic adjustments to dietary and exercise recommendations, ensuring the program remained accessible in a sparsely populated rural real-world setting and personalized to each participant's needs. Higher participation frequency was associated with greater weight loss, supporting findings that show at least 12 contacts with the primary care provider seem valuable for sustainable outcomes (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The strong correlation between program engagement and weight loss also highlights the value of structured (primary care) lifestyle interventions (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Its multifactorial approach proved effective, seen in a similar way in the past compared to single-component interventions, reinforcing the importance of continuous participation and engagement, including behavioral counseling, nutritional counseling and exercise guidance as well as social events and support. The potential benefit of GP-centered support may be especially valuable for rural populations that face unique barriers for weight-loss or lifestyle-modification programs, including limited healthcare resources, longer travel distances, and fewer community-based health initiatives (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) by offering accessible, long-term support. Following previous research (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e), the perspectives of GPs on obesity therapy and their role within this domain must be considered to enhance the effectiveness of treatment strategies. Not only the centrality of the GP within the patient\u0026rsquo;s view as well as the possibility to reach and motivate many, but also the current update of therapeutic guidelines goes hand in hand with our results, emphasizing the critical role of GPs in coordinating comprehensive care for patients with obesity.\u003c/p\u003e \u003cp\u003eBridging the gap between GP visits in rural areas, our trial also incorporated an app for self-monitoring and management. This aligns with previous research and the current German obesity guidelines, showing increased efficiency of app-based interventions especially in underserved areas (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) and therefore now recognizing digital therapeutic tools as essential components of obesity treatment, rather than optional interventions (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). By promoting self-regulation and providing personalized guidance, digital tools like the app enhance adherence and outcomes. The app fosters a personalized approach enabling participants to track their food intake, physical activity, and health metrics as well as tailored adjustments based on individual progress and needs. The app\u0026rsquo;s role in fostering self-regulation and continuous support enhances adherence and long-term results (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). However, digital exclusion may limit the app\u0026rsquo;s effectiveness, as individuals with limited digital literacy may face challenges, potentially reducing the program's overall impact (\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur findings align with previous studies that demonstrate the efficacy of multifactorial lifestyle interventions with (digital) self-management, social events and regular check-ups in promoting weight loss, cardiovascular and metabolic improvements. Notably, this trial differs from others (\u003cspan additionalcitationids=\"CR31 CR32 CR33 CR34 CR35\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e) by focusing on the percentage change in clinical parameters for each individual, rather than averaging the parameters at a specific time point across the entire cohort. This approach allows for a more nuanced understanding of individual progress and the effectiveness of the intervention over time. Despite these strengths, the study's lack of a no-intervention control group represents a limitation, especially when compared to randomized controlled trials (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e), where such a control group allows for clearer conclusions regarding the intervention's specific effects.\u003c/p\u003e \u003cp\u003eUnlike many previous studies conducted in urban or well-resourced settings, this trial specifically targeted rural populations, indicating that structured, GP-centered interventions can be effectively adapted to rural contexts. While this rural focus may limit the generalizability to urban or suburban settings, where healthcare access and lifestyle behaviors differ, the high global prevalences of obesity in rural areas (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) underscores the critical role of GPs in delivering obesity care in sparsely populated areas and broadens the applicability of GP-centered interventions there. The pragmatic design of our trial allowed for flexibility, such as the incorporation of unplanned social events and the use of a multi-centered approach, distributing patients among local physiotherapy providers, thereby reducing the administrative burden for rural GPs. Nonetheless, this flexibility introduced challenges: The management of sub-cohorts depended on the motivation and resources of individual GPs and physiotherapists, and the geographic distribution did not always align with patients\u0026rsquo; personal or work schedules. Consequently, some patients missed parts of the program, complicating the assessment of specific intervention components on trial outcomes.\u003c/p\u003e \u003cp\u003eThe HAPpEN trial reported a dropout rate of 37.8%. While participants who remained engaged demonstrated high adherence and meaningful weight loss, the attrition rate indicates that the program\u0026rsquo;s full potential may not have been realized across the entire study population. This finding is consistent with previous research, showing that adherence to lifestyle-based obesity interventions typically declines over time due to the sustained effort and self-regulation required (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). High dropout rates, common in weight management programs, may introduce selection bias, as completes are more motivated or face fewer barriers (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). Contributing factors likely included competing personal and professional commitments, lack of immediate results, fluctuating motivations, and rural healthcare barriers. Nevertheless, the strong association between program participation and weight loss underscores the importance of strategies to improve retention and maximize program impact (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFuture research should focus on strategies to address barriers to sustained engagement, such as providing motivational support and continuous feedback (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e), offering flexible participation options, and providing additional support for individuals at higher risk of dropout (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). These improvements could optimize the program\u0026rsquo;s effectiveness and increase long-term success in obesity prevention and management. In addition, a randomized controlled trial design would provide a more robust assessment of causality and strategies to optimize program retention and engagement, particularly for participants initially less motivated, should be explored to improve the intervention\u0026rsquo;s effectiveness. Finally, expanding the intervention to other underserved populations, such as urban areas with limited resources, could assess its broader applicability and identify potential areas for program refinement.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis trial demonstrated the effectiveness of a GP-centered, multifactorial intervention in promoting weight loss and improving cardiovascular and metabolic health in rural populations. Significant reductions in body weight, BMI, waist circumference, and HbA1c highlight its potential for obesity management and diabetes prevention. The positive correlation between engagement and weight loss underscores the importance of sustained participation. These findings emphasize the critical role of GPs in rural healthcare settings and support the broader applicability of GP-centered interventions in underserved areas.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003egeneral practitioner (GP), body mass index (BMI), hemoglobin A1c (HbA1c), high- and low-density lipoprotein (HDL/LDL), C-reactive protein (CrP)\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eThe HAPpEN trial has been positively approved by the ethics committee of the University of Bayreuth (Az. O 1305/1 – GB) stating: there are no ethical objections to carrying out the project. The trial is registered at the German Clinical Trial Register (DRKS00033916, March 20\u003csup\u003eth\u003c/sup\u003e 2024 retrospectively registered).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate and for publication:\u0026nbsp;\u003c/strong\u003eAll participants had given written informed consent\u0026nbsp;(consent for publication included)\u0026nbsp;to GPs prior to trial start.\u0026nbsp;The medical data of patients are assigned a pseudonym, ensuring that the collected and transmitted data cannot be traced back to the individual person’s data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials statement:\u0026nbsp;\u003c/strong\u003eThe datasets generated and analyzed during the current trial are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis work was supported by the Bavarian Federal Ministry of Health, Care and Prevention (G31i-G8000-2021/2630-23).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u0026nbsp;\u003c/strong\u003eNvS, LK, TB, RH and MH initiated the HAPpEN project. The acquisition of funding for the trial was primarily led by NvS, RH and MH. NvS and MH were responsible for coordinating patients, GPs, and researchers. All authors contributed to the intervention's design and analysis of the intervention. NvS, CB, AW, AB and MH prepared tables, while MH was responsible for creating the figures. NvS, CB, AB, MM and MH drafted the initial manuscript, which was subsequently reviewed and revised by AW, LK, TB and RH. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eWe acknowledge the Bavarian Federal Ministry of Health, Care and Prevention for funding this research and extend our gratitude to our patients and GPs for participating in this trial. We are also grateful to Susanne Tittlbach (Social and Health Science in Sport, University of Bayreuth, Bayreuth, Germany) for their support in the setup of the trial and valuable scientific discussions. Special thanks to Bria-Estella Johnson, Miriam Witthüser and Antonia Baldauf (Institute for Management in Medicine and Health Sciences, University of Bayreuth, Bayreuth, Germany) for assistance.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBl\u0026uuml;her M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019; 15(5):288\u0026ndash;98. Available from: URL: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.nature.com/articles/s41574-019-0176-8\u003c/span\u003e\u003cspan address=\"https://www.nature.com/articles/s41574-019-0176-8\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNCD Risk Factor Collaboration. Rising rural body-mass index is the main driver of the global obesity epidemic in adults. Nature 2019; 569(7755):260\u0026ndash;4. 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Impact of feedback generation and presentation on self-monitoring behaviors, dietary intake, physical activity, and weight: a systematic review and meta-analysis. Int J Behav Nutr Phys Act. 2024; 21(1):3. Available from: URL: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://ijbnpa.biomedcentral.com/articles/\u003c/span\u003e\u003cspan address=\"https://ijbnpa.biomedcentral.com/articles/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12966-023-01555-6\u003c/span\u003e\u003cspan address=\"10.1186/s12966-023-01555-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmied EA, Madanat H, Chuang E, Moody J, Ibarra L, Cervantes G et al. Factors predicting parent engagement in a family-based childhood obesity prevention and control program. 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Available from: URL: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.mdpi.com/2227-9032/6/3/70\u003c/span\u003e\u003cspan address=\"https://www.mdpi.com/2227-9032/6/3/70\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pubh","sideBox":"Learn more about [BMC Public Health](http://bmcpublichealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pubh/default.aspx","title":"BMC Public Health","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Obesity, Primary care, Body Mass Index, Rural, Weight Loss, Adults","lastPublishedDoi":"10.21203/rs.3.rs-6540216/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6540216/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Elevated prevalence of obesity has increasingly challenged public health systems worldwide, with rural areas being particularly affected. This trial aimed to evaluate the effectiveness of a general practitioner (GP)-centered, multifactorial intervention for obesity management in rural areas.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e The HAPpEN trial was a pragmatic, controlled study conducted in six rural primary care practices in Upper Franconia, Germany, with 98 adults (BMI ≥30 kg/m²) enrolled and a 12-month follow-up rate of 62.2%. Exclusion criteria included severe comorbidities restricting physical activity. The intervention combined GP-led behavioral strategies, monthly motivational counselling, nutritional guidance, physical activity, educational workshops, and digital self-monitoring with community activities to foster engagement. The control group received standard care. Primary outcomes included body weight, body mass index (BMI), waist circumference, blood pressure, heart rate, and metabolic parameters such as hemoglobin A1c (HbA1c), fasting glucose, cholesterol, triglycerides, high- and low-density lipoprotein, C-reactive protein and uric acid.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The intervention group showed significant reductions in body weight (−5.0 ± 7.7 kg, 95% CI: [-7.24, - 2.83], p\u0026lt; 0.001) and BMI (−1.7 ± 2.6 kg/m², 95% CI: [-2.48, -0.99]), p\u0026lt; 0.001] over 12 months. Waist circumference (−11.5 ± 11.1 cm, 95% CI: [-15.57, -7.34], p\u0026lt; 0.001), systolic blood pressure (−8.3 ± 14.2 mmHg, 95% CI: [-13.22, -3.30], p= 0.04) and HbA1c levels (-3.3 ± 6.2 mmol/mol, 95% CI: [-5.33, -1.30], p\u0026lt; 0.001) significantly improved, with HbA1C normalizing in many cases. A negative correlation was identified between program engagement and weight loss (r\u003csub\u003es\u003c/sub\u003e= −0.453, p\u0026lt; 0.001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The GP-centered, multifactorial intervention significantly reduced body weight and improved metabolic health markers in individuals with obesity. Sustained program engagement correlated with enhanced weight loss, underscoring the importance of structured support in rural obesity management. These findings emphasize the key role of GPs in obesity care and suggest the potential for broader application.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e: DRKS00033916, March, 20\u003csup\u003eth\u003c/sup\u003e 2024 retrospectively registered.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"HAPpEN: A pragmatic general practitioner-centered obesity management trial in rural Germany integrating multimodal lifestyle interventions","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-16 12:01:36","doi":"10.21203/rs.3.rs-6540216/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-11T19:32:52+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-11T11:16:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-07T12:26:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"38281788785525387834500542695204117871","date":"2025-08-19T08:34:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"13247194523582707674091094781452831640","date":"2025-08-16T14:21:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-13T08:47:13+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-02T15:40:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-29T00:54:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-29T00:52:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Public Health","date":"2025-04-27T11:52:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pubh","sideBox":"Learn more about [BMC Public Health](http://bmcpublichealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pubh/default.aspx","title":"BMC Public Health","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dca91977-d371-4586-89e9-f4dbbc51ffb9","owner":[],"postedDate":"May 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-10-01T15:53:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-16 12:01:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6540216","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6540216","identity":"rs-6540216","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}