S3044 The Double-Edged Sword of GLP-1 Receptor Agonists: Metabolic Benefits and GI Risks – A Systematic Review

Introduction: GLP-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes mellitus (T2DM) and obesity due to their dual benefits of glycemic control and weight reduction. However, their use is frequently limited by gastrointestinal (GI) side effects, which impact treatment adherence and quality of life. This systematic review aims to evaluate the prevalence, nature, and clinical relevance of GI adverse events associated with GLP-1 RAs, including nausea, vomiting, diarrhea, constipation, cholelithiasis, and pancreatitis, based on data from randomized trials and observational studies. Methods: A systematic search was conducted in PubMed, Embase, and Cochrane Library for studies published between January 2010 and March 2024. Inclusion criteria comprised randomized controlled trials (RCTs), cohort studies, and meta-analyses evaluating GI side effects in patients treated with GLP-1 RAs for T2DM or obesity. Keywords included “GLP-1 receptor agonists,” “gastrointestinal side effects,” “nausea,” “vomiting,” “diarrhea,” “constipation,” “cholelithiasis,” and “pancreatitis.” Data were extracted on patient demographics, type of GLP-1 RA, frequency and severity of GI events, and treatment discontinuation rates. Results: A total of 52 studies (28 RCTs, 14 cohort studies, and 10 meta-analyses) encompassing over 65,000 patients were included. Nausea was the most common adverse effect, reported in up to 50% of patients, particularly during dose escalation. Vomiting occurred in 10–20%, often contributing to early drug discontinuation. Diarrhea affected 15–25% of patients, while constipation was observed in up to 10%. Cholelithiasis was more prevalent with agents causing rapid weight loss, with a 2- to 3-fold increased risk in some cohorts. Pancreatitis was rare but reported in post-marketing surveillance data; however, meta-analyses of RCTs did not confirm a statistically significant association. Conclusion: GI adverse events with GLP-1 RAs are common but typically transient and dose-dependent. While nausea, vomiting, and diarrhea often resolve over time, gallbladder complications and rare pancreatitis cases warrant clinical vigilance. Gradual titration and individualized therapy may improve tolerability and adherence. This review highlights the importance of proactive management of GI side effects to optimize outcomes in patients receiving GLP-1 RAs for obesity and T2DM.