Efficacy of Mazdutide in Nondiabetic Adults with Overweight or Obesity: A Meta-Analysis

Efficacy of Mazdutide in Nondiabetic Adults with Overweight or Obesity: A Meta-Analysis | 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 Systematic Review Efficacy of Mazdutide in Nondiabetic Adults with Overweight or Obesity: A Meta-Analysis Mazen Negmeldin Yassin, Mohamed Saad Sayed, Omar Abdulrahman Saad, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7884657/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Mazdutide is a dual GLP-1 and glucagon receptor agonist under investigation for weight management in obesity. This meta-analysis evaluated its efficacy in nondiabetic adults with overweight or obesity. Methods We searched PubMed, Scopus, and Web of Science for randomized controlled trials (RCTs) comparing mazdutide with placebo. Primary outcomes included changes in body weight, BMI, and waist circumference. A random-effects model was used. Results Four RCTs (n = 918) were included. Mazdutide significantly reduced body weight (MD: − 7.72 kg), BMI (–2.84), waist circumference (–5.76 cm), HbA1c (–0.30%), LDL-C (–10.59 mg/dL), total cholesterol (–18.61 mg/dL), and triglycerides (–49.87 mg/dL). Conclusion Mazdutide demonstrates significant improvements in anthropometric and cardiometabolic outcomes in nondiabetic adults with overweight or obesity, supporting its role as a promising option in overweight and obesity pharmacotherapy. Body weight Mazdutide Obesity Overweight Figures Figure 1 Background Contributing to an estimated 1.6 million premature deaths annually, primarily from cardiovascular disease, diabetes, and cancer, obesity has become an escalating global crisis. More than 1.13 billion adults are expected to be living with obesity by 2030, which reflects a significant 115% increase since 2010[ 1 ]. The clinical and economic burden of obesity continues to grow, which places a substantial burden on global healthcare systems. Incretin-based therapies have advanced obesity management by improving glycemic control and weight loss, in addition to offering cardiometabolic and renal protection. However, some residual cardiometabolic risks remain despite improvements in steatosis and inflammation with these agents. Glucagon-like peptide-1 (GLP-1) receptor agonists promote weight loss primarily through appetite suppression, delayed gastric emptying, and central satiety signalling, while indirectly stimulating lipolysis via sympathetic pathways[ 2 ]. Despite their efficacy, drug discontinuation rates remain high due to treatment costs, adverse effects, and unmet expectations. These limitations have intensified efforts to develop next-generation therapies that could help sustain efficacy and improve tolerability as well as long-term use. Mazdutide (also known as IBI362 or LY3305677), a synthetic analogue of oxyntomodulin, is a novel once-weekly unimolecular dual agonist of the GLP-1 and glucagon receptors. This dual mechanism combines the appetite-suppressing effects of GLP-1 and the ability of glucagon to stimulate thermogenesis, promoting significant weight loss. In addition, the structure of mazdutide incorporates a fatty acid side chain, which prolongs its activity[ 3 ]. Crucially, mazdutide appears to avoid the hyperglycemia typically associated with selective glucagon receptor activation[ 3 ]. Comprehensive studies exploring the benefits and risks of mazdutide in overweight or obese patients are important for public health. In this systematic review and meta-analysis, we aim to evaluate the effects of mazdutide on weight reduction and cardiometabolic safety in nondiabetic adults with overweight or obesity. Methods We conducted this study while adhering to the Cochrane Handbook for Systematic Reviews and Meta-analysis of Interventions . An exhaustive search was performed on various online databases, such as PubMed, Scopus, and Web of Science, until July 2025 to identify randomized controlled trials (RCTs) investigating the use of mazdutide in nondiabetic patients with overweight or obesity. Studies satisfying our predefined inclusion criteria were included: RCTs that compared mazdutide with placebo and reported parameters of weight reduction. Primary outcomes included anthropometric measures of weight reduction, such as body weight, body mass index (BMI), and waist circumference. A random effects meta-analysis model using the DerSimonian and Laird method was utilized to pool the mean change and corresponding standard deviation (SD), reported as mean difference (MD) with 95% confidence interval (CI). Data were analyzed using STATA Corp MP17. Results Four RCTs, with a total of 918 patients, were included in this meta-analysis[ 3 – 6 ]. The studies were conducted in China between June 2020 and January 2023. The treatment period was 12 weeks in two studies, while 24-week and 48-week treatment periods were each evaluated in one study. The mean age of included adults was 35.25 years (SD: 10.9), and 443 (48.25%) were male. Mazdutide significantly reduced anthropometric measurements compared to placebo, including body weight (MD: -7.72 kg; 95% CI: -9.75 to -5.69, P < 0.001, I 2 = 90.09%; Fig. 1 A), BMI (MD: -2.84; 95% CI: -3.56 to -2.12, P < 0.001, I 2 = 90.47%; Fig. 1 B), and waist circumference (MD: -5.76 cm; 95% CI: -7.25 to -4.27, P < 0.001, I 2 = 69.75%; Fig. 1 C). In addition, mazdutide significantly lowered hemoglobin A1c (HbA1c) (MD: -0.30%; 95% CI: -0.38 to -0.22, P < 0.001, I 2 = 52.49%; Fig. 1 D) and improved lipid profile, including reductions in low-density lipoprotein cholesterol (LDL-C) (MD: -10.59 mg/dL; 95% CI: -14.08 to -7.10, P < 0.001, I 2 = 0%; Fig. 1 E), total cholesterol (TC) (MD: -18.61 mg/dL; 95% CI: -23.83 to -13.40, P < 0.001, I 2 = 7.26%; Fig. 1 F), and triglycerides (TGs) (MD: -49.87 mg/dL; 95% CI: -60.75 to -38.98, P < 0.001, I 2 = 0%; Fig. 1 G). Discussion GLP-1 receptor agonists have long been a cornerstone of pharmacotherapy for body weight management in overweight and obesity. Currently approved agents, including liraglutide, semaglutide and tirzepatide, have demonstrated robust efficacy in promoting weight reduction across several RCTs[ 7 – 9 ]. These agents have also shown pleiotropic benefits such as reductions in hepatic steatosis, systemic inflammation, and major adverse cardiovascular events. Despite these advances, residual cardiometabolic risks may persist in some patients, and treatment discontinuation rates remain substantial in real-world practice[ 10 ]. Moreover, GLP-1 receptor agonists have not shown a meaningful effect on energy expenditure—a crucial factor for optimal weight loss—in human studies, despite promising findings in preclinical models. Mazdutide has emerged as a potential treatment option by acting as a dual agonist of both GLP-1 and glucagon receptors. Multiple preclinical studies have reported improved glucose control, significant body weight reduction, and increased energy expenditure. These findings were confirmed in several RCTs, which demonstrated robust reductions in anthropometric, glycemic, and cardiometabolic parameters[ 3 – 6 ]. In our meta-analysis, mazdutide was associated with a beneficial effect on anthropometric parameters including reductions in body weight, BMI, and waist circumference. These effects are likely attributable to the anorectic effects of GLP-1 receptor agonism. Although preclinical studies suggest that glucagon receptor stimulation may increase energy expenditure, this mechanism has not yet been confirmed in human studies. In addition, mazdutide notably demonstrated glucose-lowering effects, as evidenced by a significant reduction in HbA1c levels. Furthermore, significant improvements in lipid metabolism were observed, such as reductions in LDL-C, TC, and TGs, which are explained by the notable effect of glucagon stimulation on hepatic metabolism and mitochondrial oxidative capacity. These findings highlight the potential cardiometabolic protective role of mazdutide, especially in patients with comorbidities. Strengths and limitations To our knowledge, this is the first meta-analysis to evaluate mazdutide specifically in nondiabetic adults with overweight or obesity. In addition, our meta-analysis pools data from four well-designed RCTs, producing high-quality findings of mazdutide’s efficacy in overweight or obesity. We also analyzed both anthropometric and cardiometabolic outcomes, providing a comprehensive analysis of mazdutide’s potential. However, our study has some limitations. First, as with any meta-analysis, our study is subject to the limitations of the included studies. For instance, pooled studies included phases I and II RCTs, which are early stages of clinical trials. In addition, the included trials enrolled predominantly younger Chinese adults with class I obesity and a higher proportion of male participants compared with other obesity trials. These demographic and clinical features may limit the generalizability of our findings to broader populations. At the same time, they provide valuable insights into obesity management in Asian populations, where cardiometabolic risks occur at lower BMI thresholds than in Western populations. Second, heterogeneity in dosing regimens and treatment durations across included studies may affect the interpretation of our pooled results. Third, long-term efficacy data remain uncertain due to limited off-treatment follow-up periods. Finally, subgroup analyses based on different dosing regimens and treatment durations were not feasible. Conclusion Our meta-analysis suggests that mazdutide is associated with significant weight reduction and improvements in glycemic as well as metabolic parameters compared with placebo in nondiabetic adults with overweight or obesity. These findings support mazdutide as a promising addition to the rapidly evolving landscape of overweight and obesity pharmacotherapy. Further large-scale trials are warranted to confirm these findings, assess long-term outcomes, optimize the dosing regimens, and evaluate mazdutide’s potential in other ethnicities. Statements and declarations Funding This study did not receive any funds, grants, or other support during its preparation. Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Availability of data and materials All data generated or analyzed during this study are presented in this article. On request, all additional raw data is available from the corresponding author. References World Obesity Atlas 2025. World Obes Fed n.d. https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2025 (accessed July 24, 2025). Gasoyan H, Butsch WS, Schulte R, Casacchia NJ, Le P, Boyer CB, et al. Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status. Obes Silver Spring Md 2025. https://doi.org/10.1002/oby.24331. Ji L, Gao L, Jiang H, Yang J, Yu L, Wen J, et al. Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. EClinicalMedicine 2022;54:101691. https://doi.org/10.1016/j.eclinm.2022.101691. Ji L, Jiang H, An P, Deng H, Liu M, Li L, et al. IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple ascending dose phase 1b study. EClinicalMedicine 2021;39:101088. https://doi.org/10.1016/j.eclinm.2021.101088. Ji L, Jiang H, Cheng Z, Qiu W, Liao L, Zhang Y, et al. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nat Commun 2023;14:8289. https://doi.org/10.1038/s41467-023-44067-4. Ji L, Jiang H, Bi Y, Li H, Tian J, Liu D, et al. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. N Engl J Med 2025;392:2215–25. https://doi.org/10.1056/NEJMoa2411528. Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med 2015;373:11–22. https://doi.org/10.1056/NEJMoa1411892. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021;384:989–1002. https://doi.org/10.1056/NEJMoa2032183. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387:205–16. https://doi.org/10.1056/NEJMoa2206038. Thomsen RW, Mailhac A, Løhde JB, Pottegård A. Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies. Diabetes Obes Metab 2025;27:66–88. https://doi.org/10.1111/dom.16364. Table Table 1 . Characteristics and baseline data of included studies. Study Design Country Time frame Sample Size Inclusion criteria Mazdutide doses and escalation Treatment period Follow-up period Groups Number of patients Age, years Sex, male BMI, kg/m² BMI BW, kg Waist circumference, cm SBP, mmHg DBP, mmHg HbA1c, % FPG, mg/dL TC, mg/dL LDL, mg/dL TGs, mg/dL Overweight (24 ≤ BMI < 28) Obesity (BMI ≥ 28) Ji 2021 RCT China June 2020 to January 2021 36 Adults with overweight (BMI ≥ 24 kg/m²) accompanied with hyperphagia and/or at least one obesity-related comorbidity (prediabetes, hypertension, dyslipidemia, fatty liver, weight-bearing arthralgia or dyspnea, or OSAS) or obesity (BMI ≥ 28 kg/m²) and < 5% weight loss by diet and exercise 12 weeks or longer prior to screening. 3 mg (1-2-3) 4.5 mg (1.5-3-4.5) 6 mg (2-4-6) Escalation was conducted every 4 weeks. 12 weeks 20 weeks 3 mg cohort 8 32.83 (18.76) 3 (37.5) 29.3 (2.2) 2 (25) 6 (75) 78.3 (13.7) 93.4 (8.9) 118.5 (10.5) 79.3 (9.7) 5.3 (0.6) 99.64 (4.87) 195.93 (55.28) 116.01 (55.3) 121.34 (55.8) 4.5 mg cohort 8 29.17 (8.49) 6 (75) 32.4 (3.4) 1 (12.5) 7 (87.5) 93.1 (9.9) 105.1 (8) 122 (11.3) 80.8 (7.4) 5.2 (0.2) 96.04 (6.49) 185.62 (24.36) 126.45 (27.46) 139.05 (39.86) 6 mg cohort 8 38.17 (25.46) 5 (62.5) 31.7 (2) 0 (0) 8 (100) 87.4 (8.8 104.8 (10.2) 124.1 (6.9) 81.3 (7.3) 5.3 (0.3 95.5 (12.79) 161.25 (44.86) 96.68 (13.92) 153.23 (134.63) Placebo 12 35 (8.39) 4 (33.3) 29.6 (3.4) 4 (33.3) 8 (66.7) 80.3 (13.7) 94.4 (10.2) 114.8 (9.5) 78.0 (10.8) 5.2 (0.3) 99.64 (7.57) 174.02 (55.3) 107.12 (42.15) 156.77 (133.74) Ji 2022 RCT China N/A 24 Adults with overweight (BMI ≥ 24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity (prediabetes, hypertension, dyslipidemia, fatty liver, weight bearing arthralgia or dyspnea, OSAS) or obesity (BMI ≥ 28 kg/m²) and < 5% body weight loss by diet and exercise 12 weeks or longer prior to screening. 9 mg (3-6-9) 10 mg (2.5-5-7.5-10) Escalation was conducted every 4 weeks. 12 weeks for 9 mg 16 weeks for 10 mg 20 weeks for 9 mg 24 weeks for 10 mg 9 mg cohort 8 37.9 (9.7) 2 (25) 30.1 (3.8) N/A N/A 79.8 (15.5) 97.2 (13.7) 118.3 (10.2) 80.5 (8.1) N/A N/A N/A N/A N/A 10 mg cohort 8 36 (9.1) 2 (25) 31.8 (5.1) N/A N/A 82.8 (14.1) 101.1 (11.5) 119.4 (8.8) 84.8 (7.5) N/A N/A N/A N/A N/A Placebo 8 39.9 (11.7) 3 (37.5) 29.6 (3.3) N/A N/A 80.4 (13.5) 100 (10.6) 113 (10.7) 79.5 (7.1) N/A N/A N/A N/A N/A Ji 2023 RCT China June 2021 to October 2021 248 Adults with overweight (BMI ≥ 24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity (prediabetes, hypertension, dyslipidemia, fatty liver, weight bearing arthralgia or dyspnea, OSAS) or adults with obesity (BMI ≥ 28 kg/m²). 3 mg (1.5-3) 4.5 mg (1.5-3-4.5) 6 mg (2-4-6) Escalation was conducted every 4 weeks. 24 weeks 36 weeks 3 mg cohort 62 37.2 (10.7) 27 (43.5) 31.8 (3.9) 9 (14.5) 53 (85.5) 89.8 (14.4) 104.1 (8.6) 119.2 (12) 80.9 (7.9) 5.41 (0.27) 91.89 (7.21) 184.33 (29.35) 123.74 (29.35) 168.28 (87.39) 4.5 mg cohort 63 33.6 (10) 26 (41.3) 31.8 (4.7) 11 (17.5) 52 (82.5) 89.3 (15.3) 104.7 (11.3) 116.3 (11.4) 79.4 (7.6) 5.4 (0.32) 91.89 (7.21) 185.62 (32.28) 127.61 (26.41) 132.85 (67.20) 6 mg cohort 61 35.8 (9.2) 34 (55.7) 31.7 (4) 11 (18) 50 (82) 88.5 (15.3) 103.9 (11.4) 120.8 (9.6) 81.3 (8.5) 5.34 (0.35) 91.89 (7.21) 184.33 (23.48) 125.03 (20.55) 171.24 (67.25) Placebo 62 35.5 (7.1) 32 (51.6) 32 (4.2) 9 (14.5) 53 (85.5) 0.2 (16.4) 106 (12) 118.5 (12.3) 80.9 (8.5) 5.45 (0.35) 93.69 (10.81) 189.48 (29.35) 128.90 (26.42) 174.19 (107.56) Ji 2025 RCT China November 2022 to January 2023 610 Adults with overweight (BMI ≥ 24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity (prediabetes, hypertension, dyslipidemia, fatty liver, weight bearing arthralgia or dyspnea, OSAS) or adults with obesity (BMI ≥ 28 kg/m²). 4 mg (2-4) 6 mg (2-4-6) Escalation was conducted every 4 weeks. 48 weeks 60 weeks 4 mg cohort 203 34.8 (7.9) 101 (49.8) 31 (3.5) 31 (15.3) 172 (84.7) 87.9 (14.8) 101.7 (10) 122 (11.4) 82.5 (8) 5.5 (0.35) 93.694 (9.19) 181.75 (30.94) 123.74 (27.07) 168.28 (88.57) 6 mg cohort 202 33.2 (8.2) 99 (49) 31.3 (3.8) 34 (16.8) 168 (83.2) 87.2 (14.1) 101.7 (10.1) 122.2 (12) 81.8 (7.7) 5.5 (0.34) 93.694 (8.65) 185.62 (34.8) 123.74 (27.07) 186 (115.14) Placebo 205 34.5 (7.9) 99 (48.3) 31.1 (3.3) 38 (18.5) 167 (81.5) 86.5 (13) 101.1 (9.4) 122.8 (12.1) 82.5 (7.9) 5.5 (0.33) 95.49 (9.01) 189.48 (34.8) 123.74 (27.07) 177.14 (106.28) †BMI: body mass index; BW: body weight; DBP: diastolic blood pressure; FPG: fasting plasma glucose; HbA1c: hemoglobin A1c; LDL: low-density lipoprotein; OSAS: obstructive sleep apnea syndrome; RCT: randomized controlled trial; SBP: systolic blood pressure; TC: total cholesterol; and TG: triglycerides ‡Dichotomous variables are presented as number and percentage, and continuous variables are presented as mean and standard deviation. 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1","display":"","copyAsset":false,"role":"figure","size":347124,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots of mean difference (MD) and 95% confidence interval (CI) in (A) Change in body weight from baseline, (B) Change in body mass index from baseline, C) Change in waist circumference from baseline, (D) Change in hemoglobin A1c from baseline, (E) Change in low-density lipoprotein from baseline, (F) Change in total cholesterol from baseline, and (G) Change in triglycerides from baseline\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7884657/v1/19ae3c54b3f6f90625b7023c.png"},{"id":97135355,"identity":"4ce5f3fe-1f50-4bf6-82ac-9876f03af132","added_by":"auto","created_at":"2025-12-01 09:37:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":756452,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7884657/v1/c76eb221-de5b-4737-9ad7-367f7fc0f3d8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of Mazdutide in Nondiabetic Adults with Overweight or Obesity: A Meta-Analysis","fulltext":[{"header":"Background","content":"\u003cp\u003eContributing to an estimated 1.6\u0026nbsp;million premature deaths annually, primarily from cardiovascular disease, diabetes, and cancer, obesity has become an escalating global crisis. More than 1.13\u0026nbsp;billion adults are expected to be living with obesity by 2030, which reflects a significant 115% increase since 2010[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The clinical and economic burden of obesity continues to grow, which places a substantial burden on global healthcare systems.\u003c/p\u003e\u003cp\u003eIncretin-based therapies have advanced obesity management by improving glycemic control and weight loss, in addition to offering cardiometabolic and renal protection. However, some residual cardiometabolic risks remain despite improvements in steatosis and inflammation with these agents. Glucagon-like peptide-1 (GLP-1) receptor agonists promote weight loss primarily through appetite suppression, delayed gastric emptying, and central satiety signalling, while indirectly stimulating lipolysis via sympathetic pathways[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Despite their efficacy, drug discontinuation rates remain high due to treatment costs, adverse effects, and unmet expectations. These limitations have intensified efforts to develop next-generation therapies that could help sustain efficacy and improve tolerability as well as long-term use.\u003c/p\u003e\u003cp\u003eMazdutide (also known as IBI362 or LY3305677), a synthetic analogue of oxyntomodulin, is a novel once-weekly unimolecular dual agonist of the GLP-1 and glucagon receptors. This dual mechanism combines the appetite-suppressing effects of GLP-1 and the ability of glucagon to stimulate thermogenesis, promoting significant weight loss. In addition, the structure of mazdutide incorporates a fatty acid side chain, which prolongs its activity[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Crucially, mazdutide appears to avoid the hyperglycemia typically associated with selective glucagon receptor activation[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eComprehensive studies exploring the benefits and risks of mazdutide in overweight or obese patients are important for public health. In this systematic review and meta-analysis, we aim to evaluate the effects of mazdutide on weight reduction and cardiometabolic safety in nondiabetic adults with overweight or obesity.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe conducted this study while adhering to the \u003cem\u003eCochrane Handbook for Systematic Reviews and Meta-analysis of Interventions\u003c/em\u003e. An exhaustive search was performed on various online databases, such as PubMed, Scopus, and Web of Science, until July 2025 to identify randomized controlled trials (RCTs) investigating the use of mazdutide in nondiabetic patients with overweight or obesity. Studies satisfying our predefined inclusion criteria were included: RCTs that compared mazdutide with placebo and reported parameters of weight reduction. Primary outcomes included anthropometric measures of weight reduction, such as body weight, body mass index (BMI), and waist circumference.\u003c/p\u003e\u003cp\u003eA random effects meta-analysis model using the DerSimonian and Laird method was utilized to pool the mean change and corresponding standard deviation (SD), reported as mean difference (MD) with 95% confidence interval (CI). Data were analyzed using STATA Corp MP17.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eFour RCTs, with a total of 918 patients, were included in this meta-analysis[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The studies were conducted in China between June 2020 and January 2023. The treatment period was 12 weeks in two studies, while 24-week and 48-week treatment periods were each evaluated in one study. The mean age of included adults was 35.25 years (SD: 10.9), and 443 (48.25%) were male. Mazdutide significantly reduced anthropometric measurements compared to placebo, including body weight (MD: -7.72 kg; 95% CI: -9.75 to -5.69, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;90.09%; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA), BMI (MD: -2.84; 95% CI: -3.56 to -2.12, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;90.47%; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB), and waist circumference (MD: -5.76 cm; 95% CI: -7.25 to -4.27, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;69.75%; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). In addition, mazdutide significantly lowered hemoglobin A1c (HbA1c) (MD: -0.30%; 95% CI: -0.38 to -0.22, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;52.49%; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD) and improved lipid profile, including reductions in low-density lipoprotein cholesterol (LDL-C) (MD: -10.59 mg/dL; 95% CI: -14.08 to -7.10, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE), total cholesterol (TC) (MD: -18.61 mg/dL; 95% CI: -23.83 to -13.40, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;7.26%; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF), and triglycerides (TGs) (MD: -49.87 mg/dL; 95% CI: -60.75 to -38.98, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eG).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eGLP-1 receptor agonists have long been a cornerstone of pharmacotherapy for body weight management in overweight and obesity. Currently approved agents, including liraglutide, semaglutide and tirzepatide, have demonstrated robust efficacy in promoting weight reduction across several RCTs[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. These agents have also shown pleiotropic benefits such as reductions in hepatic steatosis, systemic inflammation, and major adverse cardiovascular events. Despite these advances, residual cardiometabolic risks may persist in some patients, and treatment discontinuation rates remain substantial in real-world practice[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Moreover, GLP-1 receptor agonists have not shown a meaningful effect on energy expenditure\u0026mdash;a crucial factor for optimal weight loss\u0026mdash;in human studies, despite promising findings in preclinical models.\u003c/p\u003e\u003cp\u003eMazdutide has emerged as a potential treatment option by acting as a dual agonist of both GLP-1 and glucagon receptors. Multiple preclinical studies have reported improved glucose control, significant body weight reduction, and increased energy expenditure. These findings were confirmed in several RCTs, which demonstrated robust reductions in anthropometric, glycemic, and cardiometabolic parameters[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In our meta-analysis, mazdutide was associated with a beneficial effect on anthropometric parameters including reductions in body weight, BMI, and waist circumference. These effects are likely attributable to the anorectic effects of GLP-1 receptor agonism. Although preclinical studies suggest that glucagon receptor stimulation may increase energy expenditure, this mechanism has not yet been confirmed in human studies. In addition, mazdutide notably demonstrated glucose-lowering effects, as evidenced by a significant reduction in HbA1c levels. Furthermore, significant improvements in lipid metabolism were observed, such as reductions in LDL-C, TC, and TGs, which are explained by the notable effect of glucagon stimulation on hepatic metabolism and mitochondrial oxidative capacity. These findings highlight the potential cardiometabolic protective role of mazdutide, especially in patients with comorbidities.\u003c/p\u003e\n\u003ch3\u003eStrengths and limitations\u003c/h3\u003e\n\u003cp\u003eTo our knowledge, this is the first meta-analysis to evaluate mazdutide specifically in nondiabetic adults with overweight or obesity. In addition, our meta-analysis pools data from four well-designed RCTs, producing high-quality findings of mazdutide\u0026rsquo;s efficacy in overweight or obesity. We also analyzed both anthropometric and cardiometabolic outcomes, providing a comprehensive analysis of mazdutide\u0026rsquo;s potential.\u003c/p\u003e\u003cp\u003eHowever, our study has some limitations. First, as with any meta-analysis, our study is subject to the limitations of the included studies. For instance, pooled studies included phases I and II RCTs, which are early stages of clinical trials. In addition, the included trials enrolled predominantly younger Chinese adults with class I obesity and a higher proportion of male participants compared with other obesity trials. These demographic and clinical features may limit the generalizability of our findings to broader populations. At the same time, they provide valuable insights into obesity management in Asian populations, where cardiometabolic risks occur at lower BMI thresholds than in Western populations. Second, heterogeneity in dosing regimens and treatment durations across included studies may affect the interpretation of our pooled results. Third, long-term efficacy data remain uncertain due to limited off-treatment follow-up periods. Finally, subgroup analyses based on different dosing regimens and treatment durations were not feasible.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur meta-analysis suggests that mazdutide is associated with significant weight reduction and improvements in glycemic as well as metabolic parameters compared with placebo in nondiabetic adults with overweight or obesity. These findings support mazdutide as a promising addition to the rapidly evolving landscape of overweight and obesity pharmacotherapy. Further large-scale trials are warranted to confirm these findings, assess long-term outcomes, optimize the dosing regimens, and evaluate mazdutide\u0026rsquo;s potential in other ethnicities.\u003c/p\u003e"},{"header":"Statements and declarations","content":"\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis study did not receive any funds, grants, or other support during its preparation.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are presented in this article. On request, all additional raw data is available from the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Obesity Atlas 2025. World Obes Fed n.d. https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2025 (accessed July 24, 2025).\u003c/li\u003e\n\u003cli\u003eGasoyan H, Butsch WS, Schulte R, Casacchia NJ, Le P, Boyer CB, et al. Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status. Obes Silver Spring Md 2025. https://doi.org/10.1002/oby.24331.\u003c/li\u003e\n\u003cli\u003eJi L, Gao L, Jiang H, Yang J, Yu L, Wen J, et al. Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. EClinicalMedicine 2022;54:101691. https://doi.org/10.1016/j.eclinm.2022.101691.\u003c/li\u003e\n\u003cli\u003eJi L, Jiang H, An P, Deng H, Liu M, Li L, et al. IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple ascending dose phase 1b study. EClinicalMedicine 2021;39:101088. https://doi.org/10.1016/j.eclinm.2021.101088.\u003c/li\u003e\n\u003cli\u003eJi L, Jiang H, Cheng Z, Qiu W, Liao L, Zhang Y, et al. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nat Commun 2023;14:8289. https://doi.org/10.1038/s41467-023-44067-4.\u003c/li\u003e\n\u003cli\u003eJi L, Jiang H, Bi Y, Li H, Tian J, Liu D, et al. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. N Engl J Med 2025;392:2215\u0026ndash;25. https://doi.org/10.1056/NEJMoa2411528.\u003c/li\u003e\n\u003cli\u003ePi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med 2015;373:11\u0026ndash;22. https://doi.org/10.1056/NEJMoa1411892.\u003c/li\u003e\n\u003cli\u003eWilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021;384:989\u0026ndash;1002. https://doi.org/10.1056/NEJMoa2032183.\u003c/li\u003e\n\u003cli\u003eJastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387:205\u0026ndash;16. https://doi.org/10.1056/NEJMoa2206038.\u003c/li\u003e\n\u003cli\u003eThomsen RW, Mailhac A, L\u0026oslash;hde JB, Potteg\u0026aring;rd A. Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies. Diabetes Obes Metab 2025;27:66\u0026ndash;88. https://doi.org/10.1111/dom.16364.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Characteristics and baseline data of included studies.\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"1602\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDesign\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCountry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime frame\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSample Size\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInclusion criteria\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMazdutide doses and escalation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment period\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFollow-up period\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of patients\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex, male\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI, kg/m\u0026sup2;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBW, kg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWaist circumference, cm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSBP, mmHg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDBP, mmHg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHbA1c, %\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFPG, mg/dL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTC, mg/dL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDL, mg/dL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTGs, mg/dL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverweight (24 \u0026le; BMI \u0026lt; 28)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eObesity (BMI \u0026ge; 28)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJi 2021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 48px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 54px;\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 66px;\"\u003e\n \u003cp\u003eJune 2020 to January 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 48px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 168px;\"\u003e\n \u003cp\u003eAdults with overweight (BMI \u0026ge; 24 kg/m\u0026sup2;) accompanied with hyperphagia and/or at least one obesity-related comorbidity (prediabetes, hypertension, dyslipidemia, fatty liver, weight-bearing arthralgia or dyspnea, or OSAS) or obesity (BMI \u0026ge; 28 kg/m\u0026sup2;) and \u0026lt; 5% weight loss by diet and exercise 12 weeks or longer prior to screening.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 78px;\"\u003e\n \u003cp\u003e3 mg (1-2-3)\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;4.5 mg (1.5-3-4.5)\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;6 mg (2-4-6)\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;Escalation was conducted every 4 weeks.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 66px;\"\u003e\n \u003cp\u003e12 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 67px;\"\u003e\n \u003cp\u003e20 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e3 mg cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e32.83 (18.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e29.3 (2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e6 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e78.3 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e93.4 (8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e118.5 (10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e79.3 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.3 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e99.64 (4.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e195.93 (55.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e116.01 (55.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e121.34 (55.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e4.5 mg cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e29.17 (8.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e6 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e32.4 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e7 (87.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e93.1 (9.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e105.1 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e122 (11.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e80.8 (7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.2 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e96.04 (6.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e185.62 (24.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e126.45 (27.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e139.05 (39.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e6 mg cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e38.17 (25.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e5 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e31.7 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e8 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e87.4 (8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e104.8 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e124.1 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e81.3 (7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.3 (0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e95.5 (12.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e161.25 (44.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e96.68 (13.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e153.23 (134.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e35 (8.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e4 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e29.6 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e4 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e8 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e80.3 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e94.4 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e114.8 (9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e78.0 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.2 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e99.64 (7.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e174.02 (55.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e107.12 (42.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e156.77 (133.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJi 2022\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 54px;\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 66px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 168px;\"\u003e\n \u003cp\u003eAdults with overweight (BMI \u0026ge; 24 kg/m\u0026sup2;) accompanied by hyperphagia and/or at least one obesity-related comorbidity (prediabetes, hypertension, dyslipidemia, fatty liver, weight bearing arthralgia or dyspnea, OSAS) or obesity (BMI \u0026ge; 28 kg/m\u0026sup2;) and \u0026lt; 5% body weight loss by diet and exercise 12 weeks or longer prior to screening.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 78px;\"\u003e\n \u003cp\u003e9 mg (3-6-9)\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;10 mg (2.5-5-7.5-10)\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;Escalation was conducted every 4 weeks.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 66px;\"\u003e\n \u003cp\u003e12 weeks for 9 mg\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;16 weeks for 10 mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003e20 weeks for 9 mg\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;24 weeks for 10 mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e9 mg cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e37.9 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e30.1 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e79.8 (15.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e97.2 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e118.3 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e80.5 (8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e10 mg cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e36 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e31.8 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e82.8 (14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e101.1 (11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e119.4 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e84.8 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e39.9 (11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e29.6 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e80.4 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e100 (10.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e113 (10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e79.5 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJi 2023\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 48px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 54px;\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 66px;\"\u003e\n \u003cp\u003eJune 2021 to October 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 48px;\"\u003e\n \u003cp\u003e248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 168px;\"\u003e\n \u003cp\u003eAdults with overweight (BMI \u0026ge; 24 kg/m\u0026sup2;) accompanied by hyperphagia and/or at least one obesity-related comorbidity (prediabetes, hypertension, dyslipidemia, fatty liver, weight bearing arthralgia or dyspnea, OSAS) or adults with obesity (BMI \u0026ge; 28 kg/m\u0026sup2;).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 78px;\"\u003e\n \u003cp\u003e3 mg (1.5-3)\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;4.5 mg (1.5-3-4.5)\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;6 mg (2-4-6)\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;Escalation was conducted every 4 weeks.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 66px;\"\u003e\n \u003cp\u003e24 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 67px;\"\u003e\n \u003cp\u003e36 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e3 mg cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e37.2 (10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e27 (43.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e31.8 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e9 (14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e53 (85.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e89.8 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e104.1 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e119.2 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e80.9 (7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.41 (0.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e91.89 (7.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e184.33 (29.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e123.74 (29.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e168.28 (87.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e4.5 mg cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e33.6 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e26 (41.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e31.8 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e11 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e52 (82.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e89.3 (15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e104.7 (11.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e116.3 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e79.4 (7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.4 (0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e91.89 (7.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e185.62 (32.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e127.61 (26.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e132.85 (67.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e6 mg cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e35.8 (9.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e34 (55.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e31.7 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e11 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e50 (82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e88.5 (15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e103.9 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e120.8 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e81.3 (8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.34 (0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e91.89 (7.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e184.33 (23.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e125.03 (20.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e171.24 (67.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e35.5 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e32 (51.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e32 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e9 (14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e53 (85.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.2 (16.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e106 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e118.5 (12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e80.9 (8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.45 (0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e93.69 (10.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e189.48 (29.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e128.90 (26.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e174.19 (107.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJi 2025\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 54px;\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 66px;\"\u003e\n \u003cp\u003eNovember 2022 to January 2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 48px;\"\u003e\n \u003cp\u003e610\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 168px;\"\u003e\n \u003cp\u003eAdults with overweight (BMI \u0026ge; 24 kg/m\u0026sup2;) accompanied by hyperphagia and/or at least one obesity-related comorbidity (prediabetes, hypertension, dyslipidemia, fatty liver, weight bearing arthralgia or dyspnea, OSAS) or adults with obesity (BMI \u0026ge; 28 kg/m\u0026sup2;).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 78px;\"\u003e\n \u003cp\u003e4 mg (2-4)\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;6 mg (2-4-6)\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;Escalation was conducted every 4 weeks.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 66px;\"\u003e\n \u003cp\u003e48 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 67px;\"\u003e\n \u003cp\u003e60 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e4 mg cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e203\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e34.8 (7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e101 (49.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e31 (3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e31 (15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e172 (84.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e87.9 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e101.7 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e122 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e82.5 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.5 (0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e93.694 (9.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e181.75 (30.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e123.74 (27.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e168.28 (88.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e6 mg cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e33.2 (8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e99 (49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e31.3 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e34 (16.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e168 (83.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e87.2 (14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e101.7 (10.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e122.2 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e81.8 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.5 (0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e93.694 (8.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e185.62 (34.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e123.74 (27.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e186 (115.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e34.5 (7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e99 (48.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e31.1 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e38 (18.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e167 (81.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e86.5 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e101.1 (9.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e122.8 (12.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e82.5 (7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.5 (0.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e95.49 (9.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e189.48 (34.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e123.74 (27.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e177.14 (106.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026dagger;BMI: body mass index; BW: body weight; DBP: diastolic blood pressure; FPG: fasting plasma glucose; HbA1c: hemoglobin A1c; LDL: low-density lipoprotein; OSAS: obstructive sleep apnea syndrome; RCT: randomized controlled trial; SBP: systolic blood pressure; TC: total cholesterol; and TG: triglycerides\u003c/p\u003e\n\u003cp\u003e\u0026Dagger;Dichotomous variables are presented as number and percentage, and continuous variables are presented as mean and standard deviation.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Body weight, Mazdutide, Obesity, Overweight","lastPublishedDoi":"10.21203/rs.3.rs-7884657/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7884657/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eMazdutide is a dual GLP-1 and glucagon receptor agonist under investigation for weight management in obesity. This meta-analysis evaluated its efficacy in nondiabetic adults with overweight or obesity.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe searched PubMed, Scopus, and Web of Science for randomized controlled trials (RCTs) comparing mazdutide with placebo. Primary outcomes included changes in body weight, BMI, and waist circumference. A random-effects model was used.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eFour RCTs (n\u0026thinsp;=\u0026thinsp;918) were included. Mazdutide significantly reduced body weight (MD: \u0026minus;\u0026thinsp;7.72 kg), BMI (\u0026ndash;2.84), waist circumference (\u0026ndash;5.76 cm), HbA1c (\u0026ndash;0.30%), LDL-C (\u0026ndash;10.59 mg/dL), total cholesterol (\u0026ndash;18.61 mg/dL), and triglycerides (\u0026ndash;49.87 mg/dL).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eMazdutide demonstrates significant improvements in anthropometric and cardiometabolic outcomes in nondiabetic adults with overweight or obesity, supporting its role as a promising option in overweight and obesity pharmacotherapy.\u003c/p\u003e","manuscriptTitle":"Efficacy of Mazdutide in Nondiabetic Adults with Overweight or Obesity: A Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-22 03:19:59","doi":"10.21203/rs.3.rs-7884657/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"99deff0a-0737-41f8-aeba-41f5d1e71acc","owner":[],"postedDate":"October 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-15T08:08:42+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-22 03:19:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7884657","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7884657","identity":"rs-7884657","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}