Management of Subjects with Type 2 Diabetes Hospitalized in Internal Medicine Units: A Cluster-Randomized, Multicenter Study Before & After an Educational Program

Management of Subjects with Type 2 Diabetes Hospitalized in Internal Medicine Units: A Cluster-Randomized, Multicenter Study Before & After an Educational Program | 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 Management of Subjects with Type 2 Diabetes Hospitalized in Internal Medicine Units: A Cluster-Randomized, Multicenter Study Before & After an Educational Program Antonio Ceriello, Andrea Fontanella, Tiziana Marcella Attardo, and 23 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4842971/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Mar, 2026 Read the published version in Internal and Emergency Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Introduction: Few data are available relatively to the adherence to treatment guidelines in individuals with type 2 diabetes mellitus (T2DM) admitted to Internal Medicine Wards (IMW) while no information is available relatively to the possible efficacy of an educational intervention aimed at implementing adherence in this setting. Methods: To explore guidelines adherence and the relative impact on glycemic control in subjects with T2DM hospitalized in IMW before and after an educational intervention, we conducted a 3-phase, cluster-randomized, multicenter study. During phase 1, we retrospectively collected data from patients with T2DM hospitalized for any cause in IMW for ≥ 5 days. In phase 2, an educational training, based on the method of the educational outreach visits (EOV), was developed in 36 out of the 54 centers involved. In phase 3, done 6 months after the training, we replicated the collection of data performed in phase 1. Results: Overall, we analyzed data from 1909 and 1662 individuals with T2DM during the phase 1 and phase 3 of the study, respectively. No changes were observed in the difference between mean fasting glycemia levels at discharge vs at admission at Phase 3 comparing EOV vs NO EOV groups. A statistically significant increase in adherence to guidelines was observed from Phase 1 to Phase 3 and a trend of higher adherence was detected when comparing the EOV and the no EOV groups. A structured educational intervention improves adherence to guidelines for managing T2DM in individuals admitted to IMW but has no effect on short-term glycemic control. GLP-1RA glycemic control guidelines SGLT-2i treatment adherence type 2 diabetes Figures Figure 1 Figure 2 1. Introduction Type 2 Diabetes mellitus (T2DM) is a world pandemic increasing the risk of a range of complications, especially cardiovascular. Several studies have shown that early and aggressive control of all the most relevant risk factors, in particular hyperglycemia, dyslipidemia and hypertension can effectively prevent the development of these complications [1-3]. Obtaining optimal glycemic control, stable over time, is still a difficult result to achieve. In recent years, the availability of new safe and effective drugs has significantly changed the therapeutic approach to the disease. Patients’ phenotyping, according to a range of characteristics and comorbidities, is now the recommended standard to choose the most suitable therapy [4-8]. The results of selected studies on recently introduced classes of glucose-lowering drugs, i.e. GLP1-RA and SGLT-2i, have contributed to a further development of this strategy, with positive findings in terms of reduction of the cardiovascular risk, of hospitalizations for heart failure, and of kidney damage [4-6]. These data, together with the effects of such drugs on the risk of hypoglycaemia or in promoting weight reduction have led international Scientific Societies to produce guidelines [7-8] that have substantially changed the paradigms of the treatment of hyperglycaemia in T2DM. These guidelines recommend the opportunity to privilege, for the therapeutic choice, those classes of drugs that have demonstrated a particular effect in the specific condition that characterizes the subject with T2DM (for example, a history of previous cardiovascular event, or the presence of heart failure, or of obesity). Despite the strong evidence available and the indications of the Scientific Societies, the application of these recommendations is far from being optimal [9]. Specifically, the recent changes in the therapeutic scenario appear particularly relevant for some care settings. Among them, the area of Internal Medicine in which the complexity of the patients as well as some aspects of healthcare organization (e.g., the limited duration of hospital admissions, the transition from hospital to primary care and/or outpatient clinics) make the choice and appropriateness of treatments a challenging issue. However, in this setting, the adherence to existing guidelines on the management of patients with T2DM and the possible impact of an educational intervention have been poorly explored. To address this issue, we conducted a multicenter study to take a real-life snapshot of the management of patients with T2DM hospitalized for any cause in Italian Internal Medicine Wards (IMW) and evaluated possible deviations between the current clinical practice and the recommended guidelines ( i.e . ESC-EASD and EASD-ADA) in force at the moment of study start [5-8]. Moreover, we evaluated the effects of a specific educational program for health care personnel in IMW, aimed at improving the management of these patients and the adherence to guidelines. 2. Methods The MINDER study (Management of patIeNts with type 2 Diabetes mEllitus hospitalized in InteRnal Medicine Units) was designed and developed by the Italian Federation of Internal Medicine Hospital Clinicans’Associations (FADOI). The MINDER study was performed in 50 Italian Internal Medicine Units and carried out in the period September 2020- March 2023. Centers were selected according to their ability to prescribe all classes of antidiabetic drugs. The study was conducted according to the provisions of the Helsinki Declaration. Approval was obtained from the Ethics Committees of each participating center. It was designed as a replicate of two cross-sectional surveys interspersed with an educational program, a model successfully applied by FADOI to a number of clinical conditions [10,11,12,13]. As shown in Figure S1 , the study was composed by three steps. Phase 1 concerned a retrospective data collection pertaining to patients ≥ 18 years old with diagnosis of T2DM hospitalized for any cause in IMW for ≥ 5 days before February 2020. Given that data collection was retrospective, patients were managed according to routine clinical practice. As per study protocol, patients in treatment with insulin or patients treated with rapid acting insulin during the hospitalization or patients hospitalized for SARS-CoV-2 infection were excluded. In phase 2 an educational training, defined by the study Steering Committee, and focused on current Diabetes Guidelines recommendations and on possible deviations from the best clinical practice observed during phase 1, was conducted in 36 out of the 54 participating Centers (cluster randomization, performed at the beginning of the study). The ratio 2:1 was selected in order to offer to the majority of Centers the opportunity to undergo a program of training and therefore maximize the potential positive effect of the educational program on patient management. However, at the end of the study, the educational program was offered also to the remaining 18 Centers. The program was based on the method of the educational outreach visits (EOV), a 3-hour face-to-face meeting between a trained diabetes specialist from outside the Center and the staff of the Center itself. This method was selected being considered as one of the most effective to modify professional practice and improve health care outcomes [14]. In addition, all members of the staff of the Center received a distance learning program, to reinforce and deepen the contents of the outreach visit. Prior to the outreach visits, each diabetes specialist in charge of training (n = 9) was asked to attend a 1-day briefing workshop to gain experience with the educational program and standardize the contents to be delivered. Phase 3 occurred around 6 months after the training and concerned a new data collection replicating that performed in phase 1. In both phase 1 and phase 3, the data collection was based on the review of the medical records of the last 40 consecutive patients (in the period December 2018 – December 2020 for Phase1 and February 2022 - February 2023 for Phase 3) complying with study inclusion criteria and hospitalized in each Center. In order to minimize the “awareness bias” (i.e. the possibility that participation to the project significantly influenced clinical attitudes in phase 3), only one physician of the Centers of the “Control” group (not receiving EOV and distance learning) was made aware of the study design and procedures, and he/she was eventually supported in the study data collection by nurses or by physicians who did not have the possibility of prescribing the new categories of antidiabetic drugs. In details, collected information included: gender, age, anthropometric parameters, reason for hospitalization, concomitant diseases and relevant drug therapies, therapies for T2DM at admission to hospital and at discharge, laboratory results (fasting glycemia [FG] and glomerular filtration rate at hospital admission and at discharge, glycated hemoglobin) occurrence of hypoglycemia, duration and outcome of hospitalization. To improve quality of data collection, a study-specific electronic case report form (e-CRF) with central remote control was used. For each case, an Independent Committee of Experts assessed the adherence to guidelines of antidiabetic therapy at discharge from the hospital. In particular, two Experts, unaware of the study group (receiving or not receiving the educational program), examined each case independently. In case of discordant evaluation, the case report was examined by a third Expert. This method and the relevant specific procedures (i.e. clinical information to be analyzed, criteria for adjudication) were considered reliable and selected by the Experts prior to the beginning of the study, following an inter-rater reliability test (by Fleiss' kappa score) performed to measure the level of agreement between multiple judges for the same item (9). In particular, each Expert was asked to examine 10 clinical cases and the level of agreement was measured by using Fleiss' kappa statistics. The result achieved with this assessment (repeated two times after two cycles of training) was a moderate agreement (k< 0,5), therefore we considered that each clinical case could not be evaluated by only one Expert. 2.1 SAMPLE SIZE and Statistical Analysis Sample sizes of 1440 in Test Arm (EOV GROUP) and 720 in Control Arm (NO-EOV GROUP), which were obtained by sampling 36 centers (clusters) with an average of 40 subjects each in EOV GROUP and 18 centers with an average of 40 subjects each in NOT EOV GROUP, achieve about 80% power to detect a difference between the group means of at least 10. This estimate was calculated assuming, in phase 3, a mean difference between the first and the last measurement of fasting glycemia of around 17 mg/dL in patients hospitalized in NO-EOV GROUP Centers, and of around 27 mg/dL in patients hospitalized in EOV GROUP Centers. This estimate has been done according to previous data collected in a study performed some years ago in a very similar setting [9]. The standard deviation of subjects is about 75. The intra-cluster correlation coefficient is 0,001 (Ballpark estimate). The coefficient of variation of cluster sizes is 0,650 (Ballpark estimate). A two-sided t-test was used with a significance level of 0,050. This test used degrees of freedom based on the number of clusters. The sample size calculations were performed using the commercial software PASS 14. According to the study design, to have two mirroring phases, in the phase 1 the sample size will be of 2160 subjects, as well as in the phase 3. All test will be two-sided and performed at the significance level of α = 0.05 For primary efficacy endpoint, variation in fasting glycemia during hospitalization between the two groups of Centers (those receiving and not receiving the educational program) during phase 3 of the study, a mixed linear model with identity link function, gaussian distribution and parameterized according to a cluster-randomized design was estimated with “treatment indicator” as fixed effect, “center indicator”, (namely the cluster randomization unit), as random effect and the dependent variable computed for each patient (subject within cluster) using the change between the first and the last measurement of fasting glycemia. Point estimate of treatment difference with associated two-sided 95% Confidence Interval was reported as least-squares estimates and computed with degrees of freedom adjusted according to Kenward-Roger method in order to take into account the cluster nature of the study. The procedure GLIMMIX of SAS Software was employed for the aforementioned analyses and computations. Chi-square test for categorical parameters, and T-test or Wilcoxon rank sum test, for continuous ones, were used to compare baseline characteristic and outcomes between phases and groups (phase 3 only). The difference between variables at discharge vs. admission among the same subjects for phase 1, phase 3 EOV and phase 3 NO EOV was explored applying paired t-test (continuous) and McNemar test (categorical). To outline change in the prescription’s treatment percentage changes were calculated as To study the adherence to guidelines of antidiabetic therapy at discharge, a multilevel logistic regression was applied with the following variables as covariates: age (75 vs <75 years-old), presence of concomitant disease ((3 vs 30), previous cardiovascular event, duration of hospitalization (7 vs <7 days), FG at admission categorized as 125 mg/dL. The demographic and clinical-pathological characteristics were appropriately summarized by means of descriptive statistics. Mean, median and related distribution parameters were reported for continuous variables, while frequencies and percentages were calculated for the different categorical variables. 3. Results In Phase 1 and in Phase 3 of the study data were collected from 1909 and 1662 patients with T2DM, respectively (total number 3571). General characteristics of patients at baseline and at discharge are described in Table 1 . As confirmation of the complexity of patients with diabetes hospitalized in IMW, the study population had a mean age of 76 years, suffered a median of three chronic diseases, and around 40% of patients had a previous cardiovascular event. In both Phase 1 and in Phase 3, mean FG at the time of hospitalization was higher than that at discharge, as a result of the clinical management during the hospitalization in IMW ( Figure 1 ). We detected no significant differences for the primary endpoint of the study, i.e. the variation in FG during hospitalization between the two groups of Centers (EOV vs NO EOV) during Phase 3 of the study. The mean variation was 25,46 mg/dL in EOV group and 26,19 mg/dL in NO EOV group (p=0,93) (Point estimate of the difference = 0,73; 95% CI: -17,9;19,4) ( Figure 1 ). Table 2 shows the classes of medication for the treatment of T2DM at the admission and at discharge in Phase 1 and in Phase 3 for each group of Centers. In the EOV group a statistically significant higher percentage of patients received specific therapy for T2DM. The percentage of patients adherent to evidence-based T2DM therapy at discharge are summarized in Figure 2 . A statistically significant increase of adherence was observed from Phase1 to Phase 3 and a trend of higher adherence was detected in the EOV group VS NO EOV. Table 3 shows the results of univariate analyses and a multivariable logistic analysis aimed at evaluating potential predictors of non-adherence to optimal T2DM therapy in the Phase 3 of the study. Previous cardiovascular events and concomitant diseases (≥3) were predictors of non-adherence in Phase1 (data not shown), but not in Phase 3 ( Table 3 ). In Phase 3, age (≥75 years) and low FG at admission (< 70 mg/dL) were associated with a significant difficulty in achieving guideline-oriented management of T2DM. On the other hand, obese patients seem to receive a more appropriate T2DM treatment than patient with lower BMI. Following the educational outreach visit, participating IMW staff (both physicians and nurses) were asked to anonymously rate an overall assessment of the event based on appropriateness of the training modality and relevant contents, clarity of exposition by the tutor, and level of interaction. The mean rate of the overall level of satisfaction with the training received and reported by the participating healthcare professional was 8,4 (from 1 = unwelcome to 10 = welcome). In Figure S2 , a qualitative stratification of the level of satisfaction for each of the four aforementioned items is shown. 4. Discussion In this 3-step study, we showed that a structured educational intervention is able to improve adherence to existing guidelines for T2DM management in patients hospitalized in IMW. However, possibly due to other educational activities on these issues occurring during the study period, even those who did not receive the educational intervention still improved their adherence, though to a lesser extent than the interventional group. Glycemic control improved over time, both at admission and discharge. Relatively to the main efficacy endpoint of the study, we did not detect relevant differences in glycemic control, neither between study phases nor between educated vs non-educated groups considering the ∆ admission vs discharge. Furthermore, the NO EOV group had a larger difference than that hypothesized during study design. This latter result can be attributed to an adequately established and appropriate clinical behavior for glycemic control during hospitalization. Furthermore, improvement in the management of these patients may be ascribed to the participation of clinicians in other types of educational training interventions during the period of the study. Furthermore, we must acknowledge that we did not enroll the proposed number of individuals, largely due to the impact on hospital activities driven by the Covid-19 pandemic [15], an aspect that could have affected our results. We observed a higher use of novel glucose-lowering drugs with established cardioprotective properties after the educational program. Although this did not provide a short-term benefit on glycemic control, it is likely that the effects of increased adherence to the guidelines might provide medium or long-term benefit in terms of reduction of hard cardiovascular endpoints, which were not explored in this study. Prevalent cardiovascular events and concomitant diseases (≥3) were predictors of non-adherence in Phase 1, but not in Phase 3, likely due to the effect of the educational program. Similarly, we observed a consistent increase of the percentage of referrals to divisional ambulatory and to regional diabetes specialists in the group exposed to the educational program, suggesting an improved awareness relatively to this aspect. Other predictors of non-adherence in phase 3 were a low blood glucose level at admission and older age. Relatively to the latter variable, possible influencing factors may be the range of comorbidity, overall health status, number of drugs used, and complexity of the glucose-lowering regimen, which are more common in the elderlies [17]. A key aspect to consider when developing an educational program is the satisfaction of the professionals involved. The 4-item survey conducted among the staff of the IMW evidenced a high rate of satisfaction relatively to the appropriateness of the training modality, the clarity of exposition by the tutor, and level of interaction. This should reassure about the ability of the EOV approach to effectively deliver the necessary recommendation to the staff. However, given our study design, we cannot establish whether alternative methods of dissemination of guidelines, either active or passive, would have obtained similar results [18]. Beyond the difficulties encountered due to the Covid-19 pandemic and the limited sample size, which was powered to detect a difference in glycemic control but eventually not an increase in treatment adherence, this study presents additional, intrinsic limitations related to its design. First, we cannot rule out that doctors’ awareness of participating in this study might have made them more attentive to the management of diabetes, thus affecting results achieved in terms of compliance with recommendations (awareness bias). This concern would apply particularly to the results obtained during the phase 3. However, cluster randomization of centers, receiving or not an educational program, should reassure about the reliability of the results relative to the effect of training. Second, retrospective data collection from hospital clinical records might have missed some information required by the study protocol. On the other hand, such an approach should have limited the effect of the awareness bias, providing a reliable snapshot of real-life clinical practice. Another possible limitation is that only patients not on insulin therapy were enrolled in the study, limiting the generalization of findings. However, this choice was made with the purpose to select patients who would more plausibly benefit from an improved adherence to the guidelines. More generally, the number and the geographic distribution of the IMW involved reassure about the overall representativeness of included individuals compared with the general population with T2DM. Finally, the two study groups, those exposed to the educational intervention and the control group, differed in some baseline characteristics. Unfortunately, this risk can occur with the application of the cluster randomization. This might have modestly affected the results relative to metabolic control, but they unlikely have influenced adherence to guidelines, as documented by the predictors of adherence emerged in the phase 3 of the study. 5. Conclusions In summary, our results suggest that implementing a structured educational intervention effectively enhances adherence to established guidelines for managing T2DM in individuals admitted to the IMW, even though it does not improve short-term glycemic control. Considering the well-established cardiovascular and renal benefit of novel drugs [19,20], educational interventions aimed at improving adherence to existing guidelines might provide a long-term benefit in terms of hard outcomes for a wide population. Future, larger studies exploring this and other approaches in similar, as well as other, settings should be conducted to establish the usefulness of structured educational interventions. Declarations Acknowledgments We express our gratitude to AstraZeneca Italy, Takeda, Novo Nordisk Italy and Boehringer Ingelheim Italia S.p.A for supporting the FADOI-MINDER Study with an unrestricted research or educational grant. This research was also supported, in part, by the Italian Ministry of Health through Ricerca Corrente to IRCCS MultiMedica. Authors’ contribution Antonio Ceriello: project definition, data analysis, manuscript drafting. Andrea Fontanella: project definition, data collection. Tiziana Marcella Attardo: data collection, tutoring of educational programme. Giampietro Beltramello: tutoring of educational programme. Aldo Fierro: tutoring of educational programme. Francesco Prattichizzo: manuscript drafting. Valeria Pellegrini: manuscript drafting. Maria Serena Fiore: tutoring of educational programme. Ernesto De Menis: tutoring of educational programme. Ada Maffettone: tutoring of educational programme. Luigi Magnani: tutoring of educational programme. Ruggero Pastorelli: tutoring of educational programme. Francesco Ventrella: tutoring of educational programme. Massimo Rondana: data collection. Mauro Maurantonio: data collection. Mauro Scanferlato: data collection. Francesco Finizola: data collection. Maria Antonia Salvia: data collection. Riccardo Nevola: data collection. Giorgia Prampolini: data collection. Marco Laccetti: data collection. Franco Mastroianni: data collection. Fabio Cartabellotta: data collection. Elisa Zagarrì project definition, project and data management, data analysis, manuscript drafting. Francesco Dentali: data collection, critical revision of the manuscript. Dario Manfellotto: data collection, critical revision of the manuscript. All authors read and approved the final submitted version of to the manuscript. Conflict of interest All authors declare that they have no conflict of interest concerning the submitted manuscript. Ethical approval The study was conducted according to the provisions of the Helsinki Declaration of 1964. Approval was obtained from the Ethics Committees of each participating center. Data Availability The datasets generated during and analyzed during this study are available from the corresponding author on reasonable request. Members of the FADOI – MINDER Study Group (in alphabetical order) Alessandri Massimo/ Petri Roberta e Fabrizio Valleggi (Ospedale “Sant’Andrea” di Massa Marittima (GR)), Antonucci Giancarlo, Piredda Sabrina (Ente Ospedaliero “Galliera” di Genova), Berra Sergio Antonio /Perfetti Luca, Bracale Maria Francesca e Girola Andrea (Ospedale di Garbagnate Milanese (MI)) Burattini Maurizio/Luconi Maria Paola e Nicola Tarquinio (IRCCS Istituto Nazionale di Ricovero e Cura per Anziani INRCA di Osimo (AN)), Campagna Giuseppe, Giuliani Tommasina (Ospedale “S. Maria Goretti” di Latina), Cartabellotta Fabio/Pepe Armando (Ospedale “Buccheri-La Ferla” Fatebenefratelli di Palermo), Cavalleri Maurizio/Bernero Elena/Martino Chiara (P.O. di Chiavari (GE)), Cerci Sabrina/Leonardi Antonella/Durola Laura (Ospedale di Frascati (RM)), Corradini Paolo/Sbocchia Daniela (Ospedale "F. Petruccioli" di Pitigliano (GR)), D’Angelo Francesco/La Spina Tiziana/Dionigi Elena (Ospedale di Cernusco sul Naviglio (MI)), D’Avino Maria/Caruso Giuseppe (AORN “Cardarelli” di Napoli), De Angelis Roberta/Romanello Daniele e Sara Rotunno (Ospedale "San Pietro Fatebenefratelli” di Roma), De Carli Stefano/Spangaro Sabrina (Ospedale “Sant’Antonio” San Daniele del Friuli (UD)), De Franceschi Teresiano/Saleh Youssef (Ospedale “Santa Maria della Misericordia” di Albenga (SV)), De Giovanni Raffaella/Vogrig Nadia (AUSLRomagna, Ospedale “Cervesi” di Cattolica, Ospedale di Rimini (RN)), Dentali Francesco/Attardo Tiziana Marcella (Ospedale “Luni-Confalonieri” di Luino), Ferrari Giovanni/Asti Micaela, Nunzia Cirillo, Daniela Rebasti, Anna Rita Sorrentino (ASST Pavia, Ospedale di Broni e Stradella (PV)), Ferraro Maria (ASP Cosenza, PO Acri di Cosenza), Finizola Francesco/ Rosada Javier (USL TOSCANA NORD OVEST Ospedale “Sant’Antonio Abate” di Fivizzano (MS)), Fontanella Andrea/Bonaiuto Alessio (Ospedale Buonconsiglio Fatebenefratelli di Napoli), Gatti Pietro/Barletta Mariangela (P.O. di Brindisi) Giordano Mauro/Ciarambino Tiziana (P.O. Clinicizzato di Marcianise (CE)), Giorgi Andrea/Guarini Margherita (Presidio Ospedaliero “San Filippo Neri” di Roma). Giorgi Pierfranceschi Matteo/Migazzi Matteo (Ospedale Maggiore di Cremona), Greco Antonio/Gerdano Carmela (IRCCS "Casa Sollievo della Sofferenza" di San Giovanni Rotondo (FG)), Laccetti Marco/Coronella Concetta (AORN “Cardarelli” di Napoli), Lombardi Martina (Asl Toscana Nordovest, Ospedale di Cecina, AOU Pisana) Manfellotto Dario/Ventriglia Mariacarla (Ospedale Isola Tiberina, Gemelli-Isola, Roma). Manini Maurizio/Lillo Davide (Ospedale “San Giovanni di Dio” di Orbetello (GR)) Mastroianni Franco/ Giovanni Larizza (Ospedale Generale Regionale 'F. Miulli' di Acquaviva nelle Fonti (BA)) Maurantonio Mauro/Castellano Claudia (AOU Ospedale Civile di Baggiovara MO)) Mazzone Antonino/Brendaglia Noemi (Ospedale Civile di Legnano (MI)) Moggi Pignone Alberto/Ramundo Antonello e Bandini Giulia (A.O.U. “Careggi” di Firenze) Montagnani Andrea/Michele Caselli (Ospedale “Santa Maria della Misericordia” di Grosseto) Morana Ignazio Maria/Angela Pastore/Maria Giuseppina Pecora (ARNAS “Garibaldi” di Catania)) Muriago Michela/Dal Maso Adriana (Ospedale "Pietro Milani" Noventa Vicentina (VI)) Nevola Riccardo/Pafundi Pia Clara (University of Campania “L. Vanvitelli” di Napoli) Novati Paola/ Cottarelli Daniela (ASST RHODENSE, Presidio di Passirana di Rho) Oliva Gabriella/Andreozzi Raffaella (ASL Napoli 1 Centro, Ospedale del Mare di Napoli) Pietrantonio Filomena/Gabrielli Mariagrazia e Giampiero Marino (ASL Roma 6, Ospedale dei Castelli di Ariccia (RM)) Pirisi Mario/ Gian Paolo Fra (A.O.U. “Maggiore della Carità” di Novara, Università del Piemonte Orientale) Politi Cecilia/Mancini Concetta (Ospedale “F. Veneziale” di Isernia) Prampolini Giorgia/Turilli Marzia (Ospedale “Sant’Anna” di Castelnovo ‘Ne Monti (RE)) Renda Maurizio/Imburgia Mariangela e Giuseppe Miceli (Fondazione Istituto “G. 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Evid Rep Technol Assess (Full Rep). ; (213):1–520 Ceriello A, Catrinoiu D, Chandramouli C et al (2021) Heart failure in type 2 diabetes: current perspectives on screening, diagnosis and management. Cardiovasc Diabetol 20(1):218 Prattichizzo F, de Candia P, Ceriello A (2021) Diabetes and kidney disease: emphasis on treatment with SGLT-2 inhibitors and GLP-1 receptor agonists. Metabolism 120:154799 Tables Table 1 . General characteristics of subjects recorded at admission to IMW in Phase 1 and in Phase 3 (EOV group and NO EOV group). #:Phase 1 vs Phase 3 no EOV; §: Phase 1 vs Phase 3 EOV; ¥: Phase 3 no EOV vs Phase 3 EOV. (Wilcoxon rank sum test) VARIABLE PHASE1 (n =1909) PHASE 3 P value EOV GROUP (n =1110) NO-EOV GROUP (n= 552) Gender, n. (%) 1028 (53,8) M 881 (46,2) F 591 (53,2) M 519 (46,8) F 297 (53,8) M 255 (46,2)F # 0.98 § 0.74 ¥ 0.82 Age, years mean ± SD 76,4 ±11,2 76,4 ± 10,5 76,0 ± 11,5 # 0.38 § 0.82 ¥ 0.51 Provenance of patients, n (%) - home 1686 (88,3) 994 (89,5) 477 (86,4) # 0.23 § 0.03 ¥ 0.002 - another dept 123 (6,4) 56 (5,0) 41 (7,4) - nursing home 83 (4,3) 39 (3,5) 32 (5,8) - long-term care facility 17 (0,9) 21 (1,9) 2 (0,4) BMI, n (%) - obese (>30) 405 (21,2) 248 (22,3) 112 (20,3) # 0.58 § 0.30 ¥ 0.11 - overweight (25-30) 614 (32,2) 330 (29,7) 195 (35,3) - normal weight (18,5-24,9) 807 (42,3) 493 (44,4) 223 (40,4) - underweight (< 18,4) 83 (4,3) 39 (3,5) 22 (4,0) Previous cardiovascular event (myocardial infarction, stroke, unstable angina, surgical revascularization), n (%) 779 (40,8) 418 (37,7) 245 (44,4) # 0.13 § 0.09 ¥ 0.008 Concomitant diseases ≥3, n (%) 1064 (55,7) 555 (50,0) 313 (56,7) # 0.69 § 0.002 ¥ 0.01 HbA1c (%) ± SD 7,2 ± 1,7 7,1 ± 1,3 7,2 ± 1,6 # 0.76 § 0.009 ¥ 0.12 Outcome, n (%) Discharged 1713 (89,8) 998 (90,0) 467 (84,6) #0.007 § 0.32 ¥ 0.001 Transferred to a nursing home or other clinical facilities 78 (4,1) 40 (3,6) 38 (6,9) Transferred to another hospital 60 (3,1) 46 (4,1) 21 (3,8) Transferred to another dept. 57 (3.0) 26 (2,3) 25 (4,5) Actions specific for T2DM at the discharge, n (%) referral to general practitioner 672 (35,2) 369 (33,2) 213 (38,6) #0.001 § 0.002 ¥ 0.0002 no advice 395 (20,7) 179 (16,1) 98 (17,8) referral to divisional ambulatory (25,6) 345 (31,1) 137 (24,8) referral to regional diabetes specialist 313 (16,4) 194 (17,5) 76 (13,8) referral to other specialist consulting 41 (2,1) 23 (2,1) 28 (5,1) Duration of hospitalization, median days (IQR) 9 (6-13) 9 (7-12) 10 (7-16) #<0.0001 § 0.73 ¥ <0.0001 Table 2 . Patients in therapy for T2DM in the two phases of the study. *(hypoglucidic diet, thiazolidinediones, acarbose). ∆% = (discharge - admission)/admission*100 (McNemar test). PHASE 1 (n=1909) PHASE3 (n=1662) Admission Discharge P value EOV GROUP (n=1110) P value NO EOV GROUP (n=552) P value Admission Discharge Admission Discharge Patients in therapy for T2DM n.(%) 1559 (81,7) 1606 (84,21) 0,01 930 (83,8) 986 (88,82) <0,0001 452 (81,9) 462 (83,7) 0,33 SGLT2i 34 (1,8) 53 (2,8) 0,008 69 (6,2) 234 (21,1) <0,0001 15 (2,7) 58 (10,5) <0,0001 GLP1ra 28 (1,5) 87 (4,6) <0,0001 40 (3,6) 138 (12,4) <0,0001 20 (3,6) 63 (11,4) <0,0001 Metformin 1006 (52,7) 905 (47,4) <0,0001 630 (56,8) 518 (46,7) <0,0001 264 (47,8) 228 (41,3) 0,002 Metaglinides 191 (10,0) 150 (7,9) 0,0004 80 (7,2) 25 (2,2) <0,0001 45 (8,1) 12 (2,2) <0,0001 DPP4i 169 (8,8) 239 (12,5) <0,0001 119 (10,7) 176 (15,9) <0,0001 88 (15,9) 103 (18,7) 0,06 Sulfonylureas 247 (12,9) 140 (7,3) <0,0001 118 (10,6) 51 (4,6) <0,0001 48 (8,7) 19 (3,4) <0,0001 Insulin / 353 (18,5) / / 185 (16,7) / / 104 (18,8) / Combination 177 (9,3) 176 (9,2) 0,93 102 (9,2) 127 (11,4) 0,02 62 (11,2) 51 (9,2) 0,14 Other* 84 (4,4) 83 (4,3) 0,91 60 (5,4) 39 (3,5) 0,005 20 (3,6) 24 (4,3) 0,46 Table 3 . Univariate and multivariable multilevel logistic analysis of predictors of non-adherence in Phase 3 population. Univariate Multivariate N Not Adherence * OR IC95% Pvalue OR IC95% Pvalue Age, years =75 1026 714 2.1 1.6-2.6 <0.0001 2.0 1.6-2.6 <0.0001 Concomitant diseases, n. =3 868 564 1.1 0.9-1.4 0.31 Obesity (BMI>30) No 1302 834 Reference Reference Yes 360 199 0.7 0.5-0.9 0.003 0.7 0.5-0.9 0.04 Previous cardiovascular event No 999 619 Reference Yes 663 414 1.1 0.9-1.4 0.32 Duration of hospitalization, days =7 1312 812 1.0 0.7-1.3 0.88 FG at admission, mg/dL 125 1000 579 0.3 0.1-0.7 0.3 0.1-0.8 Supplementary Files SupplementaryMaterial.docx Cite Share Download PDF Status: Published Journal Publication published 13 Mar, 2026 Read the published version in Internal and Emergency Medicine → Version 1 posted Reviewers agreed at journal 20 Aug, 2024 Reviewers invited by journal 20 Aug, 2024 Editor assigned by journal 07 Aug, 2024 First submitted to journal 07 Aug, 2024 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. 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14:32:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4842971/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4842971/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11739-025-04238-1","type":"published","date":"2026-03-13T15:58:39+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66630117,"identity":"0b739046-8749-47a0-9dfd-387ea9564e71","added_by":"auto","created_at":"2024-10-15 04:44:42","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":114469,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMean fasting glycemia (FG) of patients in Phase 1 and in Phase 3 hospitalized in Centers of EOV group and NO-EOV group.\u003c/strong\u003eMean FG comparisons between Admission vs Discharge in Phase 1 and Phase 3 were calculated by T-test for matched data, while the variation in FG during hospitalization (∆= Mean FG discharge – admission) between Phase 1 and Phase 3, in EOV and NO EOV group and between Phase 3 EOV and NO EOV group were calculated by Multilevel model, with center as random effect. Data relative to all the comparisons are presented in the adjacent table.\u003c/p\u003e","description":"","filename":"Fig.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4842971/v1/7e8f8715af504800ba1ff22b.jpg"},{"id":66630116,"identity":"48984a6a-f797-4b1e-8f19-327ad4054d6e","added_by":"auto","created_at":"2024-10-15 04:44:42","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":116505,"visible":true,"origin":"","legend":"\u003cp\u003eComparison between Phase1 and Phase 3 EOV and NO EOV group in terms of percentage of adherence (n.) at T2DM therapy at the discharge (Multilevel Model).\u003c/p\u003e","description":"","filename":"Fig.2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4842971/v1/6d7cd322ddf2aed24b80ccd0.jpg"},{"id":104739407,"identity":"ea72fe6e-7efc-4082-969a-2bc0bbf8c66a","added_by":"auto","created_at":"2026-03-16 16:06:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1663678,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4842971/v1/aec4b2be-8b28-417b-b007-0885f42a4d73.pdf"},{"id":66630114,"identity":"c3242ad4-9736-46ad-97b4-7b9cafa59499","added_by":"auto","created_at":"2024-10-15 04:44:41","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":232878,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-4842971/v1/9e56da61fc9622006226f444.docx"}],"financialInterests":"","formattedTitle":"Management of Subjects with Type 2 Diabetes Hospitalized in Internal Medicine Units: A Cluster-Randomized, Multicenter Study Before \u0026amp; After an Educational Program","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eType 2 Diabetes mellitus (T2DM) is a world pandemic increasing the risk of a range of complications, especially cardiovascular. Several studies have shown that early and aggressive control of all the most relevant risk factors, in particular hyperglycemia, dyslipidemia and hypertension can effectively prevent the development of these complications [1-3].\u003c/p\u003e\n\u003cp\u003eObtaining optimal glycemic control, stable over time, is still a difficult result to achieve. In recent years, the availability of new safe and effective drugs has significantly changed the therapeutic approach to the disease. Patients\u0026rsquo; phenotyping, according to a range of characteristics and comorbidities, is now the recommended standard to choose the most suitable therapy [4-8].\u003c/p\u003e\n\u003cp\u003eThe results of selected studies on recently introduced classes of glucose-lowering drugs, \u003cem\u003ei.e.\u003c/em\u003e GLP1-RA and SGLT-2i, have contributed to a further development of this strategy, with positive findings in terms of reduction of the cardiovascular risk, of hospitalizations for heart failure, and of kidney damage [4-6]. These data, together with the effects of such drugs on the risk of hypoglycaemia or in promoting weight reduction have led international Scientific Societies to produce guidelines [7-8] that have substantially changed the paradigms of the treatment of hyperglycaemia in T2DM. These guidelines recommend the opportunity to privilege, for the therapeutic choice, those classes of drugs that have demonstrated a particular effect in the specific condition that characterizes the subject with T2DM (for example, a history of previous cardiovascular event, or the presence of heart failure, or of obesity).\u003c/p\u003e\n\u003cp\u003eDespite the strong evidence available and the indications of the Scientific Societies, the application of these recommendations is far from being optimal [9]. Specifically, the recent changes in the therapeutic scenario appear particularly relevant for some care settings. Among them, the area of Internal Medicine in which the complexity of the patients as well as some aspects of healthcare organization (e.g., the limited duration of hospital admissions, the transition from hospital to primary care and/or outpatient clinics) make the choice and appropriateness of treatments a challenging issue. However, in this setting, the adherence to existing guidelines\u0026nbsp;on the management of patients with T2DM and the possible impact of an educational intervention have been poorly explored.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo address this issue, we conducted a multicenter study to\u0026nbsp;take a real-life snapshot of the management of patients with T2DM hospitalized for any cause in Italian\u0026nbsp;Internal Medicine Wards (IMW) and evaluated possible deviations between the current clinical practice and the recommended guidelines (\u003cem\u003ei.e\u003c/em\u003e. ESC-EASD and EASD-ADA) in force at the moment of study start [5-8]. Moreover, we evaluated the effects of a specific educational program for health care personnel in IMW, aimed at improving the management of these patients and the adherence to guidelines.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eThe MINDER study (Management of patIeNts with type 2 Diabetes mEllitus hospitalized in InteRnal Medicine Units) was designed and developed by the Italian Federation of Internal Medicine Hospital Clinicans\u0026rsquo;Associations (FADOI). The MINDER study was performed in 50 Italian Internal Medicine Units and carried out in the period September 2020- March 2023. Centers were selected according to their ability to prescribe all classes of antidiabetic drugs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study was conducted according to the provisions of the Helsinki Declaration. Approval was obtained from the Ethics Committees of each participating center.\u003c/p\u003e\n\u003cp\u003eIt was designed as a replicate of two cross-sectional surveys interspersed with an educational program, a model successfully applied by FADOI to a number of clinical conditions [10,11,12,13].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs shown in \u003cstrong\u003eFigure S1\u003c/strong\u003e, the study was composed by three steps.\u0026nbsp;Phase 1 concerned a retrospective data collection pertaining to patients \u0026ge; 18 years old with diagnosis of T2DM hospitalized for any cause in IMW for \u0026ge; 5 days before February 2020. Given that data collection was retrospective, patients were managed according to routine clinical practice. As per study protocol, patients in treatment with insulin or patients treated with rapid acting insulin during the hospitalization or patients hospitalized for SARS-CoV-2 infection were excluded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn phase 2 an educational training, defined by the study Steering Committee, and focused on current Diabetes Guidelines recommendations and on possible deviations from the best clinical practice observed during phase 1,\u0026nbsp;was conducted in 36 out of the 54 participating Centers (cluster randomization, performed at the beginning of the study). The ratio 2:1 was selected in order to offer to the majority of Centers the opportunity to undergo a program of training and therefore maximize the potential positive effect of the educational program on patient management. However, at the end of the study, the educational program was offered also to the remaining 18 Centers. The program was\u0026nbsp;based on the method of the educational outreach visits (EOV), a 3-hour face-to-face meeting between a trained diabetes specialist from outside the Center and the staff of the Center itself. This method was selected being considered as one of the most effective to modify professional practice and improve health care outcomes [14]. In addition, all members of the staff of the Center received a distance learning program, to reinforce and deepen the contents of the outreach visit. Prior to the outreach visits, each diabetes specialist in charge of training (n = 9) was asked to attend a 1-day briefing workshop to gain experience with the educational program and standardize the contents to be delivered.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePhase 3 occurred around 6 months after the training and concerned a new data collection replicating that performed in phase 1. In both phase 1 and phase 3, the data collection was based on the review of the medical records of the last 40 consecutive patients (in the period December 2018 \u0026ndash; December 2020 for Phase1 and February 2022 - February 2023 for Phase 3) complying with study inclusion criteria and hospitalized in each Center.\u003c/p\u003e\n\u003cp\u003eIn order to minimize the \u0026ldquo;awareness bias\u0026rdquo; (i.e. the possibility that participation to the project significantly influenced clinical attitudes in phase 3), only one physician of the Centers of the \u0026ldquo;Control\u0026rdquo; group (not receiving EOV and distance learning) was made aware of the study design and procedures, and he/she was eventually supported in the study data collection by nurses or by physicians who did not have the possibility of prescribing the new categories of antidiabetic drugs.\u003c/p\u003e\n\u003cp\u003eIn details, collected information included: gender, age, anthropometric parameters, reason for hospitalization, concomitant diseases and relevant drug therapies, therapies for T2DM at admission to hospital and at discharge, laboratory results (fasting glycemia [FG] and glomerular filtration rate at hospital admission and at discharge, glycated hemoglobin) occurrence of hypoglycemia, duration and outcome of hospitalization. To improve quality of data collection, a study-specific electronic case report form (e-CRF) with central remote control was used.\u003c/p\u003e\n\u003cp\u003eFor each case, an Independent Committee of Experts assessed the adherence to guidelines of antidiabetic therapy at discharge from the hospital. In particular, two Experts, unaware of the study group (receiving or not receiving the educational program), examined each case independently. In case of discordant evaluation, the case report was examined by a third Expert. This method and the relevant specific procedures (i.e. clinical information to be analyzed, criteria for adjudication) were considered reliable and selected by the Experts prior to the beginning of the study, following an inter-rater reliability test (by Fleiss\u0026apos; kappa score) performed to measure the level of agreement between multiple judges for the same item (9). In particular, each Expert was asked to examine 10 clinical cases and the level of agreement was measured by using Fleiss\u0026apos; kappa statistics. The result achieved with this assessment (repeated two times after two cycles of training) was a moderate agreement (k\u0026lt; 0,5), therefore we considered that each clinical case could not be evaluated by only one Expert. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.1 SAMPLE SIZE and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSample sizes of 1440 in Test Arm (EOV GROUP) and 720 in Control Arm (NO-EOV GROUP), which were obtained by sampling 36 centers (clusters) with an average of 40 subjects each in EOV GROUP and 18 centers with an average of 40 subjects each in NOT EOV GROUP, achieve about 80% power to detect a difference between the group means of at least 10. This estimate was calculated assuming, in phase 3, a mean difference between the first and the last measurement of fasting glycemia of around 17 mg/dL in patients hospitalized in NO-EOV GROUP Centers, and of around 27 mg/dL in patients hospitalized in EOV GROUP Centers. This estimate has been done according to previous data collected in a study performed some years ago in a very similar setting [9]. The standard deviation of subjects is about 75. The intra-cluster correlation coefficient is 0,001 (Ballpark estimate). The coefficient of variation of cluster sizes is 0,650 (Ballpark estimate). A two-sided t-test was used with a significance level of 0,050. This test used degrees of freedom based on the number of clusters. The sample size calculations were performed using the commercial software PASS 14. According to the study design, to have two mirroring phases, in the phase 1 the sample size will be of 2160 subjects, as well as in the phase 3. All test will be two-sided and performed at the significance level of \u0026alpha; = 0.05\u003c/p\u003e\n\u003cp\u003eFor primary efficacy endpoint, variation in fasting glycemia during hospitalization between the two groups of Centers (those receiving and not receiving the educational program) during phase 3 of the study, a mixed linear model with identity link function, gaussian distribution and parameterized according to a cluster-randomized design was estimated with \u0026ldquo;treatment indicator\u0026rdquo; as fixed effect, \u0026ldquo;center indicator\u0026rdquo;, (namely the cluster randomization unit), as random effect and the dependent variable computed for each patient (subject within cluster) using the change between the first and the last measurement of fasting glycemia. Point estimate of treatment difference with associated two-sided 95% Confidence Interval was reported as least-squares estimates and computed with degrees of freedom adjusted according to Kenward-Roger method in order to take into account the cluster nature of the study. The procedure GLIMMIX of SAS Software was employed for the aforementioned analyses and computations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eChi-square test for categorical parameters, and T-test or Wilcoxon rank sum test, for continuous ones, were used to compare baseline characteristic and outcomes between phases and groups (phase 3 only).\u003c/p\u003e\n\u003cp\u003eThe difference between variables at discharge vs. admission among the same subjects for phase 1, phase 3 EOV and phase 3 NO EOV was explored applying paired t-test (continuous) and McNemar test (categorical).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo outline change in the prescription\u0026rsquo;s treatment percentage changes were calculated as\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/127393_c7e80a1c9bb65875/127393_custom_files/img1726563871.png\"\u003e\u003c/p\u003e\n\u003cp\u003eTo study the adherence to guidelines of antidiabetic therapy at discharge, a multilevel logistic regression was applied with the following variables as covariates: age (75 vs \u0026lt;75 years-old), \u0026nbsp;presence of concomitant disease ((3 vs \u0026lt;3), obesity (BMI\u0026gt;30), previous cardiovascular event, duration of hospitalization (7 vs \u0026lt;7 days), FG at admission categorized as \u0026lt;70mg/dl (reference), 70-125 mg/dL, \u0026gt;125 mg/dL.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe demographic and clinical-pathological characteristics were appropriately summarized by means of descriptive statistics. Mean, median and related distribution parameters were reported for continuous variables, while frequencies and percentages were calculated for the different categorical variables.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eIn Phase 1 and in Phase 3 of the study data were collected from 1909 and 1662 patients with T2DM, respectively (total number 3571). General characteristics of patients at baseline and at discharge are described in \u003cstrong\u003eTable 1\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eAs confirmation of the complexity of patients with diabetes hospitalized in IMW, the study population had a mean age of 76 years, suffered a median of three chronic diseases, and around 40% of patients had a previous cardiovascular event.\u003c/p\u003e\n\u003cp\u003eIn both Phase 1 and in Phase 3, mean FG at the time of hospitalization was higher than that\u0026nbsp;at\u0026nbsp;discharge, as a result of the clinical management during the hospitalization in IMW (\u003cstrong\u003eFigure 1\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe detected no significant differences for the primary endpoint of the study, \u003cem\u003ei.e.\u003c/em\u003e the variation in FG during hospitalization between the two groups of Centers (EOV vs NO EOV) during Phase 3 of the study. The mean variation was 25,46\u0026nbsp;mg/dL in EOV group\u0026nbsp;and 26,19\u0026nbsp;mg/dL in NO EOV group (p=0,93) (Point estimate of the difference = 0,73; 95%\u0026nbsp;CI: -17,9;19,4) (\u003cstrong\u003eFigure 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e shows the classes of medication for the treatment of T2DM at the admission and at discharge in Phase 1 and in Phase 3 for each group of Centers. In the EOV group a statistically significant higher percentage of patients received specific therapy for T2DM.\u003c/p\u003e\n\u003cp\u003eThe percentage of patients adherent to evidence-based T2DM therapy at discharge are summarized in \u003cstrong\u003eFigure 2\u003c/strong\u003e. A statistically significant increase of adherence was observed from Phase1 to Phase 3 and a trend of higher adherence was detected in the EOV group VS NO EOV.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e shows the results of univariate analyses and a multivariable logistic analysis aimed at evaluating potential predictors of non-adherence to optimal T2DM therapy in the Phase 3 of the study. Previous cardiovascular events and concomitant diseases (\u0026ge;3) were predictors of non-adherence in Phase1 (data not shown), but not in Phase 3 (\u003cstrong\u003eTable 3\u003c/strong\u003e). In Phase 3, age (\u0026ge;75 years) and low FG at admission (\u0026lt; 70 mg/dL) were associated with a significant difficulty in achieving guideline-oriented management of T2DM. On the other hand, obese patients seem to receive a more appropriate T2DM treatment than patient with lower BMI.\u003c/p\u003e\n\u003cp\u003eFollowing the educational outreach visit, participating IMW staff (both physicians and nurses) were asked to anonymously rate an overall assessment of the event based on appropriateness of the training modality and relevant contents, clarity of exposition by the tutor, and level of interaction. The mean rate of the overall level of satisfaction with the training received and reported by the participating healthcare professional was 8,4 (from 1 = unwelcome to 10 = welcome). In \u003cstrong\u003eFigure S2\u003c/strong\u003e, a qualitative stratification of the level of satisfaction for each of the four aforementioned items is shown.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this 3-step study, we showed that a structured educational intervention is able to improve adherence to existing guidelines for T2DM management in patients hospitalized in IMW. However, possibly due to other educational activities on these issues occurring during the study period, even those who did not receive the educational intervention still improved their adherence, though to a lesser extent than the interventional group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGlycemic control improved over time, both at admission and discharge. Relatively to the main efficacy endpoint of the study, we did not detect relevant differences in glycemic control, neither between study phases nor between educated vs non-educated groups considering the ∆ admission vs discharge. Furthermore, the NO EOV group had a larger difference than that hypothesized during study design. This latter result can be attributed to an adequately established and appropriate clinical behavior for glycemic control during hospitalization. Furthermore, improvement in the management of these patients may be ascribed to the participation of clinicians in other types of educational training interventions during the period of the study. Furthermore, we must acknowledge that we did not enroll the proposed number of individuals, largely due to the impact on hospital activities driven by the Covid-19 pandemic [15], an aspect that could have affected our results.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe observed a higher use of novel glucose-lowering drugs with established cardioprotective properties after the educational program. Although this did not provide a short-term benefit on glycemic control, it is likely that the effects of increased adherence to the guidelines might provide medium or long-term benefit in terms of reduction of hard cardiovascular endpoints, which were not explored in this study. Prevalent cardiovascular events and concomitant diseases (\u0026ge;3) were predictors of non-adherence in Phase 1, but not in Phase 3, likely due to the effect of the educational program. Similarly, we observed a consistent increase of the percentage of referrals to divisional ambulatory and to regional diabetes specialists in the group exposed to the educational program, suggesting an improved awareness relatively to this aspect. Other predictors of non-adherence in phase 3 were a low blood glucose level at admission and older age. Relatively to the latter variable, possible influencing factors may be the range of comorbidity, overall health status, number of drugs used, and complexity of the glucose-lowering regimen, which are more common in the elderlies [17]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA key aspect to consider when developing an educational program is the satisfaction of the professionals involved. The 4-item survey conducted among the staff of the IMW evidenced a high rate of satisfaction relatively to the appropriateness of the training modality, the clarity of exposition by the tutor, and level of interaction. This should reassure about the ability of the EOV approach to effectively deliver the necessary recommendation to the staff. However, given our study design, we cannot establish whether alternative methods of dissemination of guidelines, either active or passive, would have obtained similar results [18].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBeyond the difficulties encountered due to the Covid-19 pandemic and the limited sample size, which was powered to detect a difference in glycemic control but eventually not an increase in treatment adherence, this study presents additional, intrinsic limitations related to its design. First, we cannot rule out that doctors\u0026rsquo; awareness of participating in this study might have made them more attentive to the management of diabetes, thus affecting results achieved in terms of compliance with recommendations (awareness bias). This concern would apply particularly to the results obtained during the phase 3. However, cluster randomization of centers, receiving or not an educational program, should reassure about the reliability of the results relative to the effect of training. Second, retrospective data collection from hospital clinical records might have missed some information required by the study protocol. On the other hand, such an approach should have limited the effect of the awareness bias, providing a reliable snapshot of real-life clinical practice. Another possible limitation is that only patients not on insulin therapy were enrolled in the study, limiting the generalization of findings. However, this choice was made with the purpose to select patients who would more plausibly benefit from an improved adherence to the guidelines. More generally, the number and the geographic distribution of the IMW involved reassure about the overall representativeness of included individuals compared with the general population with T2DM. Finally, the two study groups, those exposed to the educational intervention and the control group, differed in some baseline characteristics. Unfortunately, this risk can occur with the application of the cluster randomization. This might have modestly affected the results relative to metabolic control, but they unlikely have influenced adherence to guidelines, as documented by the predictors of adherence emerged in the phase 3 of the study.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn summary, our results suggest that implementing a structured educational intervention effectively enhances adherence to established guidelines for managing T2DM in individuals admitted to the IMW, even though it does not improve short-term glycemic control. Considering the well-established cardiovascular and renal benefit of novel drugs [19,20], educational interventions aimed at improving adherence to existing guidelines might provide a long-term benefit in terms of hard outcomes for a wide population. Future, larger studies exploring this and other approaches in similar, as well as other, settings should be conducted to establish the usefulness of structured educational interventions. \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe express our gratitude to AstraZeneca Italy, Takeda, Novo Nordisk Italy and Boehringer Ingelheim Italia S.p.A for supporting the FADOI-MINDER Study with an unrestricted research or educational grant. This research was also supported, in part, by the Italian Ministry of Health through Ricerca Corrente to IRCCS MultiMedica.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAntonio Ceriello: project definition, data analysis, manuscript drafting. \u0026nbsp;Andrea Fontanella: project definition, data collection. Tiziana Marcella Attardo: data collection, tutoring of educational programme. Giampietro Beltramello: tutoring of educational programme. Aldo Fierro: tutoring of educational programme. Francesco Prattichizzo: manuscript drafting. Valeria Pellegrini: manuscript drafting. Maria Serena Fiore: tutoring of educational programme. Ernesto De Menis: tutoring of educational programme. Ada Maffettone: tutoring of educational programme. Luigi Magnani: tutoring of educational programme. Ruggero Pastorelli: tutoring of educational programme. Francesco Ventrella: tutoring of educational programme. Massimo Rondana: data collection. Mauro Maurantonio: data collection. Mauro Scanferlato: data collection. Francesco Finizola: data collection. Maria Antonia Salvia: data collection. Riccardo Nevola: data collection. Giorgia Prampolini: data collection. Marco Laccetti: data collection. Franco Mastroianni: data collection. Fabio Cartabellotta: data collection. Elisa Zagarr\u0026igrave; project definition, project and data management, data analysis, manuscript drafting. Francesco Dentali: data collection, critical revision of the manuscript. Dario Manfellotto: data collection, critical revision of the manuscript. \u0026nbsp;All authors read and approved the final submitted version of to the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no conflict of interest concerning the submitted manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted according to the provisions of the Helsinki Declaration of 1964. Approval was obtained from the Ethics Committees of each participating center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and analyzed during this study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMembers of the FADOI \u0026ndash; MINDER Study Group \u0026nbsp;\u003c/strong\u003e(in alphabetical order)\u003c/p\u003e\n\u003cp\u003eAlessandri Massimo/ Petri Roberta e Fabrizio Valleggi (Ospedale \u0026ldquo;Sant\u0026rsquo;Andrea\u0026rdquo; di Massa Marittima (GR)),\u003c/p\u003e\n\u003cp\u003eAntonucci Giancarlo, Piredda Sabrina (Ente Ospedaliero \u0026ldquo;Galliera\u0026rdquo; di Genova),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBerra Sergio Antonio /Perfetti Luca, Bracale Maria Francesca e Girola Andrea (Ospedale di Garbagnate Milanese (MI))\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBurattini Maurizio/Luconi Maria Paola e Nicola Tarquinio (IRCCS Istituto Nazionale di Ricovero e Cura per Anziani INRCA di Osimo (AN)),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCampagna Giuseppe, Giuliani Tommasina (Ospedale \u0026ldquo;S. Maria Goretti\u0026rdquo; di Latina),\u003c/p\u003e\n\u003cp\u003eCartabellotta Fabio/Pepe Armando (Ospedale \u0026ldquo;Buccheri-La Ferla\u0026rdquo; Fatebenefratelli di Palermo),\u003c/p\u003e\n\u003cp\u003eCavalleri Maurizio/Bernero Elena/Martino Chiara (P.O. di Chiavari (GE)),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCerci Sabrina/Leonardi Antonella/Durola Laura (Ospedale di Frascati (RM)),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCorradini Paolo/Sbocchia Daniela (Ospedale \u0026quot;F. Petruccioli\u0026quot; di Pitigliano (GR)),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eD\u0026rsquo;Angelo Francesco/La Spina Tiziana/Dionigi Elena (Ospedale di Cernusco sul Naviglio (MI)),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eD\u0026rsquo;Avino Maria/Caruso Giuseppe (AORN \u0026ldquo;Cardarelli\u0026rdquo; di Napoli),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDe Angelis Roberta/Romanello Daniele e Sara Rotunno (Ospedale \u0026quot;San Pietro Fatebenefratelli\u0026rdquo; di Roma),\u003c/p\u003e\n\u003cp\u003eDe Carli Stefano/Spangaro Sabrina (Ospedale \u0026ldquo;Sant\u0026rsquo;Antonio\u0026rdquo; San Daniele del Friuli (UD)),\u003c/p\u003e\n\u003cp\u003eDe Franceschi Teresiano/Saleh Youssef (Ospedale \u0026ldquo;Santa Maria della Misericordia\u0026rdquo; di Albenga (SV)),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDe Giovanni Raffaella/Vogrig Nadia (AUSLRomagna, Ospedale \u0026ldquo;Cervesi\u0026rdquo; di Cattolica, Ospedale di Rimini (RN)),\u003c/p\u003e\n\u003cp\u003eDentali Francesco/Attardo Tiziana Marcella (Ospedale \u0026ldquo;Luni-Confalonieri\u0026rdquo; di Luino),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFerrari Giovanni/Asti Micaela, Nunzia Cirillo, Daniela Rebasti, Anna Rita Sorrentino \u0026nbsp;(ASST Pavia, Ospedale di Broni e Stradella (PV)),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFerraro Maria (ASP Cosenza, PO Acri di Cosenza),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFinizola Francesco/ Rosada Javier (USL TOSCANA NORD OVEST Ospedale \u0026ldquo;Sant\u0026rsquo;Antonio Abate\u0026rdquo; di Fivizzano (MS)),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFontanella Andrea/Bonaiuto Alessio (Ospedale Buonconsiglio Fatebenefratelli di Napoli),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGatti Pietro/Barletta Mariangela (P.O. di Brindisi) \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGiordano Mauro/Ciarambino Tiziana (P.O. Clinicizzato di Marcianise (CE)),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGiorgi Andrea/Guarini Margherita (Presidio Ospedaliero \u0026ldquo;San Filippo Neri\u0026rdquo; di Roma).\u003c/p\u003e\n\u003cp\u003eGiorgi Pierfranceschi Matteo/Migazzi Matteo (Ospedale Maggiore di Cremona),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGreco Antonio/Gerdano Carmela (IRCCS \u0026quot;Casa Sollievo della Sofferenza\u0026quot; di San Giovanni Rotondo (FG)),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLaccetti Marco/Coronella Concetta (AORN \u0026ldquo;Cardarelli\u0026rdquo; di Napoli),\u003c/p\u003e\n\u003cp\u003eLombardi Martina (Asl Toscana Nordovest, Ospedale di Cecina, AOU Pisana)\u003c/p\u003e\n\u003cp\u003eManfellotto Dario/Ventriglia Mariacarla (Ospedale Isola Tiberina, Gemelli-Isola, Roma).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eManini Maurizio/Lillo Davide (Ospedale \u0026ldquo;San Giovanni di Dio\u0026rdquo; di Orbetello (GR))\u003c/p\u003e\n\u003cp\u003eMastroianni Franco/ Giovanni Larizza (Ospedale Generale Regionale \u0026apos;F. Miulli\u0026apos; di Acquaviva nelle Fonti (BA))\u003c/p\u003e\n\u003cp\u003eMaurantonio Mauro/Castellano Claudia (AOU Ospedale Civile di Baggiovara MO))\u003c/p\u003e\n\u003cp\u003eMazzone Antonino/Brendaglia Noemi (Ospedale Civile di Legnano (MI))\u003c/p\u003e\n\u003cp\u003eMoggi Pignone Alberto/Ramundo Antonello e Bandini Giulia (A.O.U. \u0026ldquo;Careggi\u0026rdquo; di Firenze)\u003c/p\u003e\n\u003cp\u003eMontagnani Andrea/Michele Caselli (Ospedale \u0026ldquo;Santa Maria della Misericordia\u0026rdquo; di Grosseto)\u003c/p\u003e\n\u003cp\u003eMorana Ignazio Maria/Angela Pastore/Maria Giuseppina Pecora (ARNAS \u0026ldquo;Garibaldi\u0026rdquo; di Catania))\u003c/p\u003e\n\u003cp\u003eMuriago Michela/Dal Maso Adriana (Ospedale \u0026quot;Pietro Milani\u0026quot; Noventa Vicentina (VI)) \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNevola Riccardo/Pafundi Pia Clara (University of Campania \u0026ldquo;L. Vanvitelli\u0026rdquo; di Napoli)\u003c/p\u003e\n\u003cp\u003eNovati Paola/ Cottarelli Daniela (ASST RHODENSE, Presidio di Passirana di Rho)\u003c/p\u003e\n\u003cp\u003eOliva Gabriella/Andreozzi Raffaella (ASL Napoli 1 Centro, Ospedale del Mare di Napoli)\u003c/p\u003e\n\u003cp\u003ePietrantonio Filomena/Gabrielli Mariagrazia e Giampiero Marino\u0026nbsp;(ASL Roma 6, Ospedale dei Castelli di Ariccia (RM))\u003c/p\u003e\n\u003cp\u003ePirisi Mario/ Gian Paolo Fra (A.O.U. \u0026ldquo;Maggiore della Carit\u0026agrave;\u0026rdquo; di Novara, Universit\u0026agrave; del Piemonte Orientale)\u003c/p\u003e\n\u003cp\u003ePoliti Cecilia/Mancini Concetta (Ospedale \u0026ldquo;F. Veneziale\u0026rdquo; di Isernia)\u003c/p\u003e\n\u003cp\u003ePrampolini Giorgia/Turilli Marzia (Ospedale \u0026ldquo;Sant\u0026rsquo;Anna\u0026rdquo; di Castelnovo \u0026lsquo;Ne Monti (RE))\u003c/p\u003e\n\u003cp\u003eRenda Maurizio/Imburgia Mariangela e Giuseppe Miceli (Fondazione Istituto \u0026ldquo;G. Giglio\u0026rdquo; di Cefal\u0026ugrave; (PA))\u003c/p\u003e\n\u003cp\u003eRondana Massimo/Santoro Fabrizio (ASFO di Spilimbergo (PN))\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSalvia Maria Antonia/Martino Rosamaria (P.O. \u0026ldquo;San Salvatore\u0026rdquo; di Mistretta (ME))\u003c/p\u003e\n\u003cp\u003eScanferlato Mauro/Cirillo Margherita (AULSS 4 Veneto Orientale, Ospedale di Portogruaro (VE)),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTonizzo Maurizio/ Copat Maria e Zanier Ada (Ospedale Santa Maria degli Angeli\u0026quot; di Pordenone)\u003c/p\u003e\n\u003cp\u003eTrojani Cristina/Antonini Raffaella e Gabriella Fantini (Ospedale \u0026ldquo;Ceccarini\u0026rdquo; di Riccione (RN))\u003c/p\u003e\n\u003cp\u003eZoratti Raffaele/Pizzin Cristina (Ospedale di Palmanova, Presidio Ospedaliero Latisana-Palmanova ASUFC - Udine)\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348:383\u0026ndash;393\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaede P, Lund-Andersen H, Parving HH, Pedersen O (2008) Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 358:580\u0026ndash;591\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eG\u0026aelig;de P, Oellgaard J, Carstensen B, Rossing P, Lund-Andersen H, Parving HH, Pedersen O (2016) Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia 59:2298\u0026ndash;2307\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStandl E, Schnell O, McGuire DK, Ceriello A, Ryd\u0026eacute;n L (2017) Integration of recent evidence into management of patients with atherosclerotic cardiovascular disease and type 2 diabetes. Lancet Diabetes Endocrinol 5:391\u0026ndash;402\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCosentino F, Ceriello A, Baeres FMM et al (2018) Addressing cardiovascular risk in type 2 diabetes mellitus: a report from the European Society of Cardiology Cardiovascular Roundtable. Eur Heart J. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehy677\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehy677\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e[Epub ahead of print]\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchnell O, Standl E, Catrinoiu D et al (2019) Report from the 4th Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes \u0026amp; Cardiovascular Disease (D\u0026amp;CVD) EASD Study Group. Cardiovasc Diabetol 18:30\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavies MJ, D'Alessio DA, Fradkin J et al (2018) Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 41:2669\u0026ndash;2701\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArnett DK, Blumenthal RS, Albert MA et al (2019) 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. ; pii: S0735-1097(19)33877-X. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jacc.2019.03.010\u003c/span\u003e\u003cspan address=\"10.1016/j.jacc.2019.03.010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. [Epub ahead of print]\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGabler M, Picker N, Geier S et al (2021) Guideline Adherence and Associated Outcomes in the Treatment of Type 2 Diabetes Mellitus Patients With an Incident Cardiovascular Comorbidity: An Analysis Based on a Large German Claims Dataset. Diabetes Ther. ; (4):1209\u0026ndash;1226\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGulli G, Frasson S, Borzi V et al (2014) Effectiveness of an educational intervention on the management of type 2 diabetic patients hospitalized in Internal Medicine: results from the FADOI-DIAMOND study. Acta Diabetol 137:137\u0026ndash;148\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrancato D, Biondi B, Attardo TM et al (2022) Management of Hypothyroidism in Internal Medicine: Patient Profile and Effects of an Educational Programme in the Cluster- Randomized FADOI TIAMO Study. Front. Endocrinol 13:839300\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCivardi G, Zucco F, Valerio A et al (2015) Pain management in internal medicine and effects of a standardised educational intervention: the FADOI-DOMINO study. Int J Clin Pract 69(1):33\u0026ndash;40\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlasi F, Iori I, Bulfoni A, Corrao S, Costantino S, Legnani D (2008) Does implementation of pneumonia guidelines improve patient management? A three-phase study in Italian Internal Medicine departments. Eur Resp J 32:902\u0026ndash;910\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO\u0026rsquo;Brien MA, Rogers S, Jarntvedt G et al (2007) Educational outreach visits effects on professional practice and health care outcomes. Cochrane Database Syst Rev 17(4):Cd000409\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDi Marco M, Miano N, Marchisello S et al (2023) Indirect Effects of the COVID-19 Pandemic on In-Hospital Outcomes among Internal Medicine Departments: A Double-Center Retrospective Study. J Clin Med 12(16):5304\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRusso G, Di Bartolo P, Candido R et al (2023) The AMD ANNALS: A continuous initiative for the improvement of type 2 diabetes care. Diabetes Res Clin Pract 199:110672\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePandya N, Hames E, Sandhu S (2020) Challenges and Strategies for Managing Diabetes in the Elderly in Long-Term Care Settings. Diabetes Spectr 33(3):236\u0026ndash;245\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCormack L, Sheridan S, Lewis M et al (2013) Communication and dissemination strategies to facilitate the use of health-related evidence. Evid Rep Technol Assess (Full Rep). ; (213):1\u0026ndash;520\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCeriello A, Catrinoiu D, Chandramouli C et al (2021) Heart failure in type 2 diabetes: current perspectives on screening, diagnosis and management. Cardiovasc Diabetol 20(1):218\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrattichizzo F, de Candia P, Ceriello A (2021) Diabetes and kidney disease: emphasis on treatment with SGLT-2 inhibitors and GLP-1 receptor agonists. Metabolism 120:154799\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. General characteristics of subjects recorded at admission to IMW in Phase 1 and in Phase 3 (EOV group and NO EOV group). #:Phase 1 vs Phase 3 no EOV; \u0026sect;: Phase 1 vs Phase 3 EOV; \u0026yen;: Phase 3 no EOV vs Phase 3 EOV. (Wilcoxon rank sum test)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"1317\" style=\"margin-right: calc(11%); width: 89%;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" rowspan=\"2\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVARIABLE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" rowspan=\"2\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePHASE1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n =1909)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.845220030349015%\" colspan=\"2\" valign=\"top\" style=\"width: 36.0555%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePHASE 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" rowspan=\"2\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.13896457765667%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEOV GROUP\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n =1110)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.86103542234333%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNO-EOV GROUP\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n= 552)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender, n. (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e1028 (53,8) M\u003c/p\u003e\n \u003cp\u003e881 (46,2) F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e591 (53,2) M\u003c/p\u003e\n \u003cp\u003e519 (46,8) F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e297 (53,8) M\u003c/p\u003e\n \u003cp\u003e255 (46,2)F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e# 0.98\u003c/p\u003e\n \u003cp\u003e\u0026sect; 0.74\u003c/p\u003e\n \u003cp\u003e\u0026yen; 0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, years mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e76,4 \u0026plusmn;11,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e76,4 \u0026plusmn; 10,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e76,0 \u0026plusmn; 11,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e# 0.38\u003c/p\u003e\n \u003cp\u003e\u0026sect; 0.82\u003c/p\u003e\n \u003cp\u003e\u0026yen; 0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eProvenance of patients, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e- home\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e1686 (88,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e994 (89,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e477 (86,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" rowspan=\"4\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e# 0.23\u003c/p\u003e\n \u003cp\u003e\u0026sect; 0.03\u003c/p\u003e\n \u003cp\u003e\u0026yen; 0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.33069481090589%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e- another dept\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.391380826737027%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e123 (6,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.215479331574318%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e56 (5,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.06244503078276%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e41 (7,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.33069481090589%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e- nursing home\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.391380826737027%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e83 (4,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.215479331574318%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e39 (3,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.06244503078276%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e32 (5,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.33069481090589%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e- long-term care facility\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.391380826737027%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e17 (0,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.215479331574318%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e21 (1,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.06244503078276%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e2 (0,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e- obese (\u0026gt;30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e405 (21,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e248 (22,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e112 (20,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" rowspan=\"4\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e# 0.58\u003c/p\u003e\n \u003cp\u003e\u0026sect; 0.30\u003c/p\u003e\n \u003cp\u003e\u0026yen; 0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.33069481090589%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e- overweight (25-30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.391380826737027%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e614 (32,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.215479331574318%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e330 (29,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.06244503078276%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e195 (35,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.33069481090589%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e- normal weight (18,5-24,9)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.391380826737027%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e807 (42,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.215479331574318%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e493 (44,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.06244503078276%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e223 (40,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.33069481090589%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e- underweight (\u0026lt; 18,4)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.391380826737027%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e83 (4,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.215479331574318%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e39 (3,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.06244503078276%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e22 (4,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrevious cardiovascular event (myocardial infarction, stroke, unstable angina, surgical revascularization), n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e779 (40,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e418 (37,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e245 (44,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e# 0.13\u003c/p\u003e\n \u003cp\u003e\u0026sect; 0.09\u003c/p\u003e\n \u003cp\u003e\u0026yen; 0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConcomitant diseases \u0026ge;3, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e1064 (55,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e555 (50,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e313 (56,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e# 0.69\u003c/p\u003e\n \u003cp\u003e\u0026sect; 0.002\u003c/p\u003e\n \u003cp\u003e\u0026yen; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHbA1c (%) \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e7,2 \u0026plusmn; 1,7\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e7,1 \u0026plusmn; 1,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e7,2 \u0026plusmn; 1,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e# 0.76\u003c/p\u003e\n \u003cp\u003e\u0026sect; 0.009\u003c/p\u003e\n \u003cp\u003e\u0026yen; 0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDischarged\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e1713 (89,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e998 (90,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e467 (84,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e#0.007\u003c/p\u003e\n \u003cp\u003e\u0026sect; 0.32\u003c/p\u003e\n \u003cp\u003e\u0026yen; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTransferred to a nursing home or other clinical facilities\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e78 (4,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e40 (3,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e38 (6,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTransferred to another hospital\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e60 (3,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e46 (4,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e21 (3,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTransferred to another dept.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e57 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e26 (2,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e25 (4,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eActions specific for T2DM at the discharge, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ereferral to general practitioner\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e672 (35,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e369 (33,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e213 (38,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e#0.001\u003c/p\u003e\n \u003cp\u003e\u0026sect; 0.002\u003c/p\u003e\n \u003cp\u003e\u0026yen; 0.0002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eno advice\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e395 (20,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e179 (16,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e98 (17,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ereferral to divisional ambulatory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e(25,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e345 (31,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e137 (24,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ereferral to regional diabetes specialist\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e313 (16,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e194 (17,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e76 (13,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ereferral to other specialist consulting\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e41 (2,1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e23 (2,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e28 (5,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.144157814871015%\" valign=\"top\" style=\"width: 28.6973%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of hospitalization, median days (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.277693474962064%\" valign=\"top\" style=\"width: 15.5898%;\"\u003e\n \u003cp\u003e9 (6-13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.125948406676782%\" valign=\"top\" style=\"width: 18.4893%;\"\u003e\n \u003cp\u003e9 (7-12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.719271623672231%\" valign=\"top\" style=\"width: 18.033%;\"\u003e\n \u003cp\u003e10 (7-16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.732928679817906%\" valign=\"top\" style=\"width: 20.2649%;\"\u003e\n \u003cp\u003e#\u0026lt;0.0001\u003c/p\u003e\n \u003cp\u003e\u0026sect; 0.73\u003c/p\u003e\n \u003cp\u003e\u0026yen; \u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e. \u0026nbsp; Patients in therapy for T2DM in the two phases of the study. *(hypoglucidic diet, thiazolidinediones, acarbose).\u0026nbsp;∆%\u0026nbsp;= (discharge - admission)/admission*100 (McNemar test).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"1341\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.304250559284116%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.12677106636838%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePHASE 1 (n=1909)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.36614466815809%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePHASE3 (n=1662)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.202833706189411%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.295081967213115%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.953800298062593%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdmission \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.953800298062593%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDischarge \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.27123695976155%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.566318926974663%\" colspan=\"2\" valign=\"top\" style=\"width: 20.5882%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEOV GROUP (n=1110) \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.538002980625931%\" rowspan=\"2\" valign=\"top\" style=\"width: 10.8261%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.225037257824145%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNO EOV GROUP (n=552)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.19672131147541%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.06015037593985%\" valign=\"top\" style=\"width: 11.1233%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdmission\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.63157894736842%\" valign=\"top\" style=\"width: 10.2002%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDischarge\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.06015037593985%\" valign=\"top\" style=\"width: 10.3749%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdmission \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.24812030075188%\" valign=\"top\" style=\"width: 14.7815%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDischarge\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.313432835820896%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients in therapy for T2DM n.(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e1559 (81,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e1606 (84,21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.283582089552239%\" valign=\"top\"\u003e\n \u003cp\u003e0,01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 11.1233%;\"\u003e\n \u003cp\u003e930 (83,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\" style=\"width: 10.2002%;\"\u003e\n \u003cp\u003e986 (88,82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.8261%;\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.3749%;\"\u003e\n \u003cp\u003e452 (81,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.626865671641792%\" valign=\"top\" style=\"width: 14.7815%;\"\u003e\n \u003cp\u003e462 (83,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.208955223880597%\" valign=\"top\"\u003e\n \u003cp\u003e0,33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.313432835820896%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSGLT2i\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e34 (1,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e53 (2,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.283582089552239%\" valign=\"top\"\u003e\n \u003cp\u003e0,008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 11.1233%;\"\u003e\n \u003cp\u003e69 (6,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\" style=\"width: 10.2002%;\"\u003e\n \u003cp\u003e234 (21,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.8261%;\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.3749%;\"\u003e\n \u003cp\u003e15 (2,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.626865671641792%\" valign=\"top\" style=\"width: 14.7815%;\"\u003e\n \u003cp\u003e58 (10,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.208955223880597%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.313432835820896%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGLP1ra\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e28 (1,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e87 (4,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.283582089552239%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 11.1233%;\"\u003e\n \u003cp\u003e40 (3,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\" style=\"width: 10.2002%;\"\u003e\n \u003cp\u003e138 (12,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.8261%;\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.3749%;\"\u003e\n \u003cp\u003e20 (3,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.626865671641792%\" valign=\"top\" style=\"width: 14.7815%;\"\u003e\n \u003cp\u003e63 (11,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.208955223880597%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.313432835820896%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetformin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e1006 (52,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e905 (47,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.283582089552239%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 11.1233%;\"\u003e\n \u003cp\u003e630 (56,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\" style=\"width: 10.2002%;\"\u003e\n \u003cp\u003e518 (46,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.8261%;\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.3749%;\"\u003e\n \u003cp\u003e264 (47,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.626865671641792%\" valign=\"top\" style=\"width: 14.7815%;\"\u003e\n \u003cp\u003e228 (41,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.208955223880597%\" valign=\"top\"\u003e\n \u003cp\u003e0,002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.313432835820896%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetaglinides\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e191 (10,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e150 (7,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.283582089552239%\" valign=\"top\"\u003e\n \u003cp\u003e0,0004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 11.1233%;\"\u003e\n \u003cp\u003e80 (7,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\" style=\"width: 10.2002%;\"\u003e\n \u003cp\u003e25 (2,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.8261%;\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.3749%;\"\u003e\n \u003cp\u003e45 (8,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.626865671641792%\" valign=\"top\" style=\"width: 14.7815%;\"\u003e\n \u003cp\u003e12 (2,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.208955223880597%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.313432835820896%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDPP4i\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e169 (8,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e239 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.283582089552239%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 11.1233%;\"\u003e\n \u003cp\u003e119 (10,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\" style=\"width: 10.2002%;\"\u003e\n \u003cp\u003e176 (15,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.8261%;\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.3749%;\"\u003e\n \u003cp\u003e88 (15,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.626865671641792%\" valign=\"top\" style=\"width: 14.7815%;\"\u003e\n \u003cp\u003e103 (18,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.208955223880597%\" valign=\"top\"\u003e\n \u003cp\u003e0,06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.313432835820896%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSulfonylureas\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e247 (12,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e140 (7,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.283582089552239%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 11.1233%;\"\u003e\n \u003cp\u003e118 (10,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\" style=\"width: 10.2002%;\"\u003e\n \u003cp\u003e51 (4,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.8261%;\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.3749%;\"\u003e\n \u003cp\u003e48 (8,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.626865671641792%\" valign=\"top\" style=\"width: 14.7815%;\"\u003e\n \u003cp\u003e19 (3,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.208955223880597%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.313432835820896%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInsulin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e353 (18,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.283582089552239%\" valign=\"top\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 11.1233%;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\" style=\"width: 10.2002%;\"\u003e\n \u003cp\u003e185 (16,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.8261%;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.3749%;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.626865671641792%\" valign=\"top\" style=\"width: 14.7815%;\"\u003e\n \u003cp\u003e104 (18,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.208955223880597%\" valign=\"top\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.313432835820896%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCombination\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e177 (9,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e176 (9,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.283582089552239%\" valign=\"top\"\u003e\n \u003cp\u003e0,93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 11.1233%;\"\u003e\n \u003cp\u003e102 (9,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\" style=\"width: 10.2002%;\"\u003e\n \u003cp\u003e127 (11,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.8261%;\"\u003e\n \u003cp\u003e0,02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.3749%;\"\u003e\n \u003cp\u003e62 (11,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.626865671641792%\" valign=\"top\" style=\"width: 14.7815%;\"\u003e\n \u003cp\u003e51 (9,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.208955223880597%\" valign=\"top\"\u003e\n \u003cp\u003e0,14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.313432835820896%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e84 (4,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\"\u003e\n \u003cp\u003e83 (4,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.283582089552239%\" valign=\"top\"\u003e\n \u003cp\u003e0,91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 11.1233%;\"\u003e\n \u003cp\u003e60 (5,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.970149253731343%\" valign=\"top\" style=\"width: 10.2002%;\"\u003e\n \u003cp\u003e39 (3,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.8261%;\"\u003e\n \u003cp\u003e0,005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.552238805970148%\" valign=\"top\" style=\"width: 10.3749%;\"\u003e\n \u003cp\u003e20 (3,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.626865671641792%\" valign=\"top\" style=\"width: 14.7815%;\"\u003e\n \u003cp\u003e24 (4,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.208955223880597%\" valign=\"top\"\u003e\n \u003cp\u003e0,46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. Univariate and multivariable multilevel logistic analysis of predictors of non-adherence in Phase 3 population.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"1271\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.94488188976378%\" colspan=\"4\" valign=\"top\" style=\"width: 44.1568%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53543307086614%\" colspan=\"3\" valign=\"top\" style=\"width: 26.9582%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.519685039370078%\" colspan=\"3\" valign=\"top\" style=\"width: 26.7339%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.24547600314713%\" colspan=\"2\" valign=\"top\" style=\"width: 28.1602%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.07081038552321%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.588512981904012%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot Adherence *\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.799370574350905%\" valign=\"top\" style=\"width: 14.5416%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.149488591660111%\" valign=\"top\" style=\"width: 8.3907%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIC95%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.644374508261212%\" valign=\"top\" style=\"width: 7.9344%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePvalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.248623131392605%\" valign=\"top\" style=\"width: 8.2316%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.49724626278521%\" valign=\"top\" style=\"width: 6.6255%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIC95%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.75609756097561%\" valign=\"top\" style=\"width: 9.0191%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePvalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.763779527559056%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.503937007874017%\" valign=\"top\" style=\"width: 6.6333%;\"\u003e\n \u003cp\u003e\u0026lt;75\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.078740157480315%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.598425196850394%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e319\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.881889763779528%\" colspan=\"2\" valign=\"top\" style=\"width: 19.1542%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.653543307086615%\" valign=\"top\" style=\"width: 7.9344%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.755905511811024%\" colspan=\"2\" valign=\"top\" style=\"width: 13.8845%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.763779527559056%\" valign=\"top\" style=\"width: 9.0191%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.588235294117647%\" valign=\"top\" style=\"width: 6.6333%;\"\u003e\n \u003cp\u003e\u0026gt;=75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.549019607843137%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e1026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.686274509803921%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e714\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.980392156862745%\" valign=\"top\" style=\"width: 14.5416%;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.647058823529411%\" valign=\"top\" style=\"width: 8.3907%;\"\u003e\n \u003cp\u003e1.6-2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.509803921568627%\" valign=\"top\" style=\"width: 7.9344%;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.294117647058823%\" valign=\"top\" style=\"width: 8.2316%;\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.588235294117647%\" valign=\"top\" style=\"width: 6.6255%;\"\u003e\n \u003cp\u003e1.6-2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.156862745098039%\" valign=\"top\" style=\"width: 9.0191%;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.763779527559056%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eConcomitant diseases, n.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.503937007874017%\" valign=\"top\" style=\"width: 6.6333%;\"\u003e\n \u003cp\u003e\u0026lt;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.078740157480315%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e794\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.598425196850394%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e469\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.881889763779528%\" colspan=\"2\" valign=\"top\" style=\"width: 19.1542%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.653543307086615%\" valign=\"top\" style=\"width: 7.9344%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.519685039370078%\" colspan=\"3\" rowspan=\"2\" valign=\"top\" style=\"width: 26.7339%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.713896457765667%\" valign=\"top\" style=\"width: 6.6333%;\"\u003e\n \u003cp\u003e\u0026gt;=3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.438692098092645%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e868\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.798365122615802%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.310626702997276%\" valign=\"top\" style=\"width: 14.5416%;\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.57493188010899%\" valign=\"top\" style=\"width: 8.3907%;\"\u003e\n \u003cp\u003e0.9-1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.16348773841962%\" valign=\"top\" style=\"width: 7.9344%;\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.763779527559056%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eObesity (BMI\u0026gt;30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.503937007874017%\" valign=\"top\" style=\"width: 6.6333%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.078740157480315%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e1302\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.598425196850394%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e834\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.881889763779528%\" colspan=\"2\" valign=\"top\" style=\"width: 19.1542%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.653543307086615%\" valign=\"top\" style=\"width: 7.9344%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.755905511811024%\" colspan=\"2\" valign=\"top\" style=\"width: 13.8845%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.763779527559056%\" valign=\"top\" style=\"width: 9.0191%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.588235294117647%\" valign=\"top\" style=\"width: 6.6333%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.549019607843137%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e360\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.686274509803921%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e199\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.980392156862745%\" valign=\"top\" style=\"width: 14.5416%;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.647058823529411%\" valign=\"top\" style=\"width: 8.3907%;\"\u003e\n \u003cp\u003e0.5-0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.509803921568627%\" valign=\"top\" style=\"width: 7.9344%;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.294117647058823%\" valign=\"top\" style=\"width: 8.2316%;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.588235294117647%\" valign=\"top\" style=\"width: 6.6255%;\"\u003e\n \u003cp\u003e0.5-0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.156862745098039%\" valign=\"top\" style=\"width: 9.0191%;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.763779527559056%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrevious cardiovascular event\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.503937007874017%\" valign=\"top\" style=\"width: 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width=\"17.438692098092645%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e663\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.798365122615802%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e414\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.310626702997276%\" valign=\"top\" style=\"width: 14.5416%;\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.57493188010899%\" valign=\"top\" style=\"width: 8.3907%;\"\u003e\n \u003cp\u003e0.9-1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.16348773841962%\" valign=\"top\" style=\"width: 7.9344%;\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.508130081300813%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of hospitalization, days\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.975609756097562%\" valign=\"top\" style=\"width: 6.6333%;\"\u003e\n \u003cp\u003e\u0026lt;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.008130081300813%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.260162601626018%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e221\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.20731707317073%\" colspan=\"2\" valign=\"top\" style=\"width: 19.1542%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.040650406504065%\" valign=\"top\" style=\"width: 7.9344%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.713896457765667%\" valign=\"top\" style=\"width: 6.6333%;\"\u003e\n \u003cp\u003e\u0026gt;=7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.438692098092645%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e1312\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.798365122615802%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e812\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.310626702997276%\" valign=\"top\" style=\"width: 14.5416%;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.57493188010899%\" valign=\"top\" style=\"width: 8.3907%;\"\u003e\n \u003cp\u003e0.7-1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.16348773841962%\" valign=\"top\" style=\"width: 7.9344%;\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.763779527559056%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFG at admission, mg/dL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.503937007874017%\" valign=\"top\" style=\"width: 6.6333%;\"\u003e\n \u003cp\u003e\u0026lt;70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.078740157480315%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.598425196850394%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.881889763779528%\" colspan=\"2\" valign=\"top\" style=\"width: 19.1542%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.653543307086615%\" rowspan=\"3\" valign=\"top\" style=\"width: 7.9344%;\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.755905511811024%\" colspan=\"2\" valign=\"top\" style=\"width: 13.8845%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.763779527559056%\" rowspan=\"3\" valign=\"top\" style=\"width: 9.0191%;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.438502673796792%\" valign=\"top\" style=\"width: 6.6333%;\"\u003e\n \u003cp\u003e70-125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.112299465240643%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e549\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.390374331550802%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e371\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.155080213903743%\" valign=\"top\" style=\"width: 14.5416%;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.245989304812834%\" valign=\"top\" style=\"width: 8.3907%;\"\u003e\n \u003cp\u003e0.1-0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.219251336898396%\" valign=\"top\" style=\"width: 8.2316%;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.438502673796792%\" valign=\"top\" style=\"width: 6.6255%;\"\u003e\n \u003cp\u003e0.2-0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.438502673796792%\" valign=\"top\" style=\"width: 6.6333%;\"\u003e\n \u003cp\u003e\u0026gt;125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.112299465240643%\" valign=\"top\" style=\"width: 10.8886%;\"\u003e\n \u003cp\u003e1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.390374331550802%\" valign=\"top\" style=\"width: 7.8614%;\"\u003e\n \u003cp\u003e579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.155080213903743%\" valign=\"top\" style=\"width: 14.5416%;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.245989304812834%\" valign=\"top\" style=\"width: 8.3907%;\"\u003e\n \u003cp\u003e0.1-0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.219251336898396%\" valign=\"top\" style=\"width: 8.2316%;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.438502673796792%\" valign=\"top\" style=\"width: 6.6255%;\"\u003e\n \u003cp\u003e0.1-0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"internal-and-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"iaem","sideBox":"Learn more about [Internal and Emergency Medicine](http://link.springer.com/journal/11739)","snPcode":"11739","submissionUrl":"https://www.editorialmanager.com/iaem/default.aspx","title":"Internal and Emergency Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"GLP-1RA, glycemic control, guidelines, SGLT-2i, treatment adherence, type 2 diabetes","lastPublishedDoi":"10.21203/rs.3.rs-4842971/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4842971/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eFew data are available relatively to the adherence to treatment guidelines in individuals with type 2 diabetes mellitus (T2DM) admitted to Internal Medicine Wards (IMW) while no information is available relatively to the possible efficacy of an educational intervention aimed at implementing adherence in this setting.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eTo explore guidelines adherence and the relative impact on glycemic control in subjects with T2DM hospitalized in IMW before and after an educational intervention, we conducted a 3-phase, cluster-randomized, multicenter study. During phase 1, we retrospectively collected data from patients with T2DM hospitalized for any cause in IMW for ≥ 5 days. In phase 2, an educational training, based on the method of the educational outreach visits (EOV), was developed in 36 out of the 54 centers involved. In phase 3, done 6 months after the training, we replicated the collection of data performed in phase 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOverall, we analyzed data from 1909 and 1662 individuals with T2DM during the phase 1 and phase 3 of the study, respectively. No changes were observed in the difference between mean fasting glycemia levels at discharge \u003cem\u003evs\u003c/em\u003e at admission at Phase 3 comparing EOV vs NO EOV groups. A statistically significant increase in adherence to guidelines was observed from Phase 1 to Phase 3 and a trend of higher adherence was detected when comparing the EOV and the no EOV groups. A structured educational intervention improves adherence to guidelines for managing T2DM in individuals admitted to IMW but has no effect on short-term glycemic control.\u003c/p\u003e","manuscriptTitle":"Management of Subjects with Type 2 Diabetes Hospitalized in Internal Medicine Units: A Cluster-Randomized, Multicenter Study Before \u0026amp; After an Educational Program","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-15 04:44:36","doi":"10.21203/rs.3.rs-4842971/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-08-20T10:33:29+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-20T06:11:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-07T18:00:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Internal and Emergency Medicine","date":"2024-08-07T04:41:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"internal-and-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"iaem","sideBox":"Learn more about [Internal and Emergency Medicine](http://link.springer.com/journal/11739)","snPcode":"11739","submissionUrl":"https://www.editorialmanager.com/iaem/default.aspx","title":"Internal and Emergency Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"0929cf28-89df-4865-b166-72e8f03d755c","owner":[],"postedDate":"October 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-16T16:02:49+00:00","versionOfRecord":{"articleIdentity":"rs-4842971","link":"https://doi.org/10.1007/s11739-025-04238-1","journal":{"identity":"internal-and-emergency-medicine","isVorOnly":false,"title":"Internal and Emergency Medicine"},"publishedOn":"2026-03-13 15:58:39","publishedOnDateReadable":"March 13th, 2026"},"versionCreatedAt":"2024-10-15 04:44:36","video":"","vorDoi":"10.1007/s11739-025-04238-1","vorDoiUrl":"https://doi.org/10.1007/s11739-025-04238-1","workflowStages":[]},"version":"v1","identity":"rs-4842971","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4842971","identity":"rs-4842971","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}