S728 Meta-Analysis of Survodutide: Impact on Satiety, Appetite, Gastrointestinal Adverse Effects, and Drug Discontinuation

Introduction: Survodutide acts as a glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) dual receptor agonist, reducing appetite and promoting weight loss. Due to promising results, the US Food and Drug Administration (FDA) has expedited its development, and Phase 3 trials are underway for multiple indications. While these drugs represent a revolutionary advancement, gastrointestinal (GI) side effects are a major cause of drug discontinuation. This study examines survodutide’s GI effects and their impact on adherence. Methods: A systematic search in PubMed and Google Scholar for full-text articles published until May 2025, evaluating survodutide's effect in treating diabetes, obesity, and metabolic dysfunction-associated steatohepatitis, was done. A meta-analysis using a random-effects model with Restricted Maximum Likelihood (REML) in R (metafor package) calculated odds ratios (OR), 95% confidence intervals (CI), heterogeneity (I²), and P-values. Outcomes included decreased appetite, early satiety, nausea, vomiting, diarrhea, constipation, abdominal pain, and drug discontinuation from GI side effects. Results: A total of 1,225 patients from 5 RCTs were included, with 978 patients receiving survodutide in different doses, and 247 in the control group. Survodutide-treated patients showed higher odds of decreased appetite (OR = 3.39, P = 0.0004, 95% CI: 0.54–1.90, I² = 19.6%). The odds of early satiety were higher but not statistically significant (OR = 3.37, P = 0.065, 95% CI: -0.08 to 2.51, I² = 0%). The odds of experiencing nausea (OR = 6.14, P < 0.001, 95% CI: 1.45–2.18, I² = 0%), vomiting (OR = 10.15, P < 0.001, 95% CI: 1.66–2.97, I² = 0%), and diarrhea (OR = 2.66, P < 0.001, 95% CI: 0.59–1.37, I² = 0%) were significantly higher in the survodutide arm. Constipation (OR = 1.67, P = 0.368, 95% CI: -0.61 to 1.63, I² = 61.6%) and abdominal pain (OR = 3.11, P = 0.142, 95% CI: -0.38 to 2.65, I² = 0%) did not show statistically significant differences. Odds of treatment discontinuation due to gastrointestinal side effects were markedly elevated (OR = 9.24, P < 0.001, 95% CI: 1.14–3.31, I² = 0%). Conclusion: While showing potential for reducing appetite, survodutide may increase the odds of nausea, vomiting, and diarrhea. Its poor gastrointestinal tolerability, which can lead to drug discontinuation, along with variability in dose-escalation and side-effect reporting, warrants further investigation. These findings underscore the need to enhance survodutide's safety profile by optimizing its dosing regimen.