ROLE OF GLP-1 AGONISTS IN THE TREATMENT OF OBESITY-RELATED GASTROINTESTINAL DISORDERS

Abstract

Background: Obesity-related gastrointestinal disorders—gastro-esophageal reflux disease (GERD), non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS), are rising in parallel with global adiposity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally licensed for type 2 diabetes and weight control, have pleiotropic gut–liver effects that may alleviate these complications.
Objective: To quantify the efficacy and safety of GLP-1 RAs in adults with obesity (BMI ≥ 30 kg m⁻²) and physician-diagnosed GERD, NAFLD or IBS.
Methods: Systematic review and random-effects meta-analysis of randomized controlled trials (RCTs) ≥ 12 weeks identified in MEDLINE, Embase and CENTRAL (inception–June 2024). Primary outcomes were change in validated gastrointestinal symptom scores, absolute weight loss and serum alanine/aspartate aminotransferase (ALT/AST).
Results: Fifteen RCTs (n = 3,142) evaluating semaglutide 2.4 mg or liraglutide 3.0 mg versus placebo were retained. Pooled mean weight loss was –7.2 kg (95 % CI –9.3 to –5.1). Gastrointestinal symptom scores improved by ≥50 % in 70 % of participants (risk ratio 2.1; 95 % CI 1.7–2.6). ALT and AST fell by 21 U L⁻¹ and 18 U L⁻¹, respectively, with fibrosis regression in 30 % of NAFLD cases. Adverse events were mostly mild nausea (10.3 %) or diarrhea (5.2 %); no excess of serious gastrointestinal events was observed.
Conclusions: GLP-1 receptor agonists confer clinically meaningful reductions in body weight and in GERD, NAFLD and IBS symptoms among obese adults, with an acceptable tolerability profile. Longer-term trials are warranted to confirm durability and safety beyond two years.