Efficacy and safety of semaglutide on weight loss in obese or overweight patients without diabetes: A systematic review and meta-analysis of randomized controlled trials

Gao, Xueqin; Hua, Xiaoli; Wang, Xu; Xu, Wanbin; Shi, Chen; Gu, Ming

doi:10.3389/fphar.2022.935823

Cited by 22 publications

(14 citation statements)

References 63 publications

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“… 16 Additional data from recent reviews and/or meta-analyses show that semaglutide is effective in people with overweight or obesity with or without T2DM. 51–53 These findings support those of the present analysis in demonstrating the benefits of semaglutide 2.4 mg versus liraglutide.…”

Section: Discussionsupporting

confidence: 89%

Semaglutide 2.4 Mg for the Management of Overweight and Obesity: Systematic Literature Review and Meta-Analysis

Smith¹,

Hardy²,

Mitchell³

et al. 2022

DMSO

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Purpose Semaglutide has demonstrated safe and effective weight loss for overweight and obesity, including participants with concomitant type 2 diabetes mellitus (T2DM), in randomized placebo-controlled trials (RCTs). We conducted a systematic literature review (SLR) and network meta-analyses (NMA) to compare weekly semaglutide 2.4 mg with pharmacological comparators for weight management in overweight or obesity. Methods The SLR was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. NMAs were performed to compare weight change for semaglutide 2.4 mg with comparators using data identified in the SLR. The populations of interest were total population, normal glucose tolerance, non-T2DM, pre-diabetes, and T2DM. Included outcomes were weight change from baseline (CFB, %) at 52 weeks and proportion of participants losing ≥5% baseline fasting body weight at 12 weeks (at full therapeutic dose). Results The SLR identified 108 RCTs examining non-surgical interventions, of which 41 were considered for inclusion in the NMAs. In all populations, semaglutide 2.4 mg was associated with a greater percentage weight CFB with 52 weeks of treatment versus all available comparators. In all populations, semaglutide was associated with a higher likelihood of participants losing ≥5% of baseline fasting body weight at 12 weeks versus all available comparators. Conclusion In NMA, semaglutide 2.4 mg demonstrated effective weight loss (≥5%) in the total population and all subpopulations of glucose tolerance versus active comparators. Semaglutide is an effective treatment that may address unmet need in the management of overweight and obesity.

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Section: Discussionsupporting

confidence: 89%

Semaglutide 2.4 Mg for the Management of Overweight and Obesity: Systematic Literature Review and Meta-Analysis

Smith¹,

Hardy²,

Mitchell³

et al. 2022

DMSO

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“…The treatment of obesity with semaglutide has been a focus of previous systematic reviews, exploring the efficacy and safety of subcutaneous semaglutide in patients with excess of weight with or without type 2 diabetes [15][16][17]. Since then, additional publications shed light on the impact of semaglutide as a game changer in the treatment of obesity.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Efficacy and safety of once-weekly subcutaneous semaglutide in adults with overweight or obesity: systematic review with meta-analysis

Dorneles,

Algeri,

Lauterbach

et al. 2024

Exp Clin Endocrinol Diabetes

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Background: To evaluate the efficacy and safety of once-weekly subcutaneous semaglutide treatment in overweight or obese patients without type 2 diabetes. Methods: Randomized clinical trials that accessed the impact of once-weekly semaglutide on body weight and safety outcomes in overweight or obese patients were retrieved from Pubmed, EMBASE, and Lilacs up to November 2023. Risk of bias was assessed with RoB 2.0, and certainty of evidence (CoE) with GRADE. We conducted a random-effects meta-analysis. Results: We included ten publications with 22.155 patients. Semaglutide decreased relative body weight (MD: -11.80; 95%CI: -13.53 to -10.07; CoE: High), absolute body weight (MD: -11.58; 95%CI: -13.25 to -9.90; CoE: High) and BMI (MD: -4.15; 95%CI: -4.85 to -3.45; CoE: High). Semaglutide also increased the proportion of patients who achieved 5%, 10% and 15% of weight loss ([weight loss ≥5%: RR 2.29, 95% CI: 1.88 to 2.80; CoE: High]; [weight loss ≥10%: RR 4.54, 95% CI: 3.45 to 5.98; CoE: High]; [weight loss ≥15%: RR 8.29, 95%CI: 5.54 to 12.39; CoE: High]). Semaglutide leads to small risk to adverse events (RR: 1.03; 95%CI: 1 to 1.06; CoE: High), no difference in the serious adverse events (RR: 1.07; 95%CI: 0.70 – 1.62; CoE: Low), but increases in the risk to discontinued treatment (RR: 2.03; 95%CI: 1.87 – 2.20; CoE: High) and gastrointestinal adverse events (RR: 3.26; 95%CI: 1.99 – 5.34; CoE: Moderate). Conclusion: This up-to-date systematic review highlights that once-weekly semaglutide treatment resulted in clinically important weight loss, becoming a promising adjuvant therapy to treat obesity.

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“…76 A meta-analysis of five trials that included 3642 individuals living with obesity but without T2D demonstrated that treatment with semaglutide 2.4 mg weekly was associated with a 12.3% placebo-subtracted body weight loss (Table 3B). 75 A network meta- 3B). 78 Among adults with biopsy-confirmed NASH and liver fibrosis of stage F1, F2, or F3, semaglutide 0.4 mg s.c. versus placebo daily for 72 weeks improved steatohepatitis resolution with no worsening of fibrosis, but there was no between-group difference in improvement of fibrosis stage.…”

Section: High Dose Semaglutidementioning

confidence: 99%

“… 76 A meta‐analysis of five trials that included 3642 individuals living with obesity but without T2D demonstrated that treatment with semaglutide 2.4 mg weekly was associated with a 12.3% placebo‐subtracted body weight loss (Table 3B). 75 A network meta‐analysis of semaglutide 2.4 mg for management of obesity in individuals without T2D found a greater percentage body weight loss compared to liraglutide 3.0 mg, naltrexone/buproprion, orlistat, and phentermine/topiramate 114 . The 68‐week OASIS 1 trial demonstrated that individuals with obesity who were treated with oral semaglutide 50 mg plus lifestyle intervention lost 12.7% more body weight than a group treated with placebo plus lifestyle intervention (Table 3B).…”

Section: High‐dose Glp‐1rasmentioning

confidence: 99%

Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists

Goldenberg,

Gilbert,

Manjoo

et al. 2023

Obesity Reviews

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SummaryType 2 diabetes (T2D), obesity, and nonalcoholic fatty liver disease/nonalacoholic steatohepatitis (NAFLD/NASH) share mutual causalities. Medications that may offer clinical benefits to all three conditions are being developed. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are approved for the management of T2D and obesity and there is great interest in evaluating higher doses of available GLP‐1RAs and developing novel GLP‐1RA‐based co‐agonists to provide greater reductions in glycated hemoglobin (HbA1c) and body weight as well as modifying NAFLD/NASH complications in clinically meaningful ways. High‐dose GLP‐1RAs and multi‐hormonal strategies including GLP‐1R agonism have either already been approved or are in development for managing T2D, obesity, or NASH. We provide a mechanistic outline with a detailed summary of the available clinical data and ongoing trials that are adjudicating the impact of high‐dose GLP‐1RAs, unimolecular, and multimolecular GLP‐1R‐based co‐agonists in populations living with T2D, obesity, or NASH. The available trial findings are aligned with preclinical observations, showing clinical efficacy and safety thus providing optimism for the expansion of GLP‐1R‐based drug classes for managing the triad of T2D, obesity and NASH. Development, access, and wide‐spread utilization of these new therapeutic approaches will offer important opportunities to markedly improve the collective global burden of T2D, obesity, and NASH.

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Efficacy and safety of semaglutide on weight loss in obese or overweight patients without diabetes: A systematic review and meta-analysis of randomized controlled trials

Cited by 22 publications

References 63 publications

Semaglutide 2.4 Mg for the Management of Overweight and Obesity: Systematic Literature Review and Meta-Analysis

Semaglutide 2.4 Mg for the Management of Overweight and Obesity: Systematic Literature Review and Meta-Analysis

Efficacy and safety of once-weekly subcutaneous semaglutide in adults with overweight or obesity: systematic review with meta-analysis

Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists

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