Efficacy and safety of survodutide on glycemic control and weight loss in adults: A systematic review and meta-analysis.
This systematic review and meta-analysis pooled data from six randomized controlled trials (RCTs) involving 1,272 adults to evaluate the efficacy and safety of survodutide, a glucagon/GLP-1 receptor co-agonist peptide, for glycemic control and weight loss. Compared with placebo, the study found that survodutide was associated with statistically significant reductions in HbA1c, fasting glucagon levels, body weight, and waist circumference. Subgroup analyses suggested that higher total weekly doses and longer treatment durations (greater than 16 weeks) were associated with more pronounced effects on body weight and waist circumference, while greater HbA1c reductions were linked to higher doses. Secondary outcomes including BMI, total cholesterol, triglycerides, and blood pressure also showed modest reductions. On the safety side, survodutide was associated with a significantly higher risk of treatment discontinuation due to adverse events, with gastrointestinal events being the most frequently reported, though serious adverse events did not increase significantly. Limitations include the small number of included trials (six), limited participant diversity, and varying treatment durations across studies. The authors call for larger, longer, multicenter RCTs to confirm these findings across broader populations.
Why this grade: Based on six RCTs in humans with pooled analysis, but limited by a small trial count (n=6), modest total sample size (n=1,272), and heterogeneity in doses and durations, preventing a strong-human grade.
Aim This meta-analysis aimed to evaluate the efficacy and safety of survodutide on glycemic control and weight loss in adults. Methods We systematically searched PubMed, Embase, the Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov for randomized controlled trials (RCTs) evaluating the efficacy and safety of survodutide up to 12 July 2025. The primary outcomes were changes in glycated haemoglobin (HbA1c), fasting glucagon levels, body weight, waist circumference, along with the incidence of adverse events (AEs). Secondary outcomes included body mass index (BMI), lipid profiles, and blood pressure. Results Six RCTs involving 1272 participants were included in this meta-analysis. Compared with placebo, survodutide significantly reduced HbA1c (weighted mean difference [WMD]: -0.66%, 95% confidence interval [CI] [-1.08, -0.23], p = 0.002) and fasting glucagon levels (WMD: -7 pmol/L, 95% CI [-10.3, -3.69], p = 0.016). Greater reductions were observed in the subgroup receiving a total weekly dose of >2.4 mg compared with the subgroup receiving ≤2.4 mg weekly. Survodutide also significantly decreased body weight (WMD: -6.7 kg, 95% CI [-10.0, -3.4], p 2.4 mg) and longer treatment durations (>16 weeks). Additionally, significant reductions were observed in BMI, and modest reductions were noted in total cholesterol, triglycerides, and blood pressure. However, survodutide was associated with a higher risk of treatment discontinuation due to AEs, with gastrointestinal AEs being the most common, although there was no significant increase in the incidence of serious AEs. Conclusions Survodutide significantly reduced HbA1c, body weight, and waist circumference. A greater reduction in HbA1c was specifically associated with a higher total weekly dose (>2.4 mg), while more pronounced effects on body weight and waist circumference were observed with both higher doses and longer treatment durations (>16 weeks). However, it is crucial to highlight the significant increase in gastrointestinal AEs and the associated risk of treatment discontinuation. Further large-scale, multicentre, long-term, and high-quality RCTs are necessary to validate these results in diverse populations.
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