JUNIOR RESEARCHERS · Jul 14, 2026
Gastrointestinal and Extra-Metabolic Effects of GLP-1-Based Therapies: A Narrative Review
By Geetha SS, Abbas SMNE, Saadi AR et al.
The GLP-1 receptor agonists (GLP-1RAs) have become important drugs for use in the management of type 2 diabetes mellitus and obesity. Their metabolic effects, such as glycemic control and weight loss, are widely recognized, however, the growing evidence reveals that these therapies have substantial gastrointestinal and extra-metabolic effects via intricate interactions amongst the gut–pancreas–brain axis. This review offers a physiological evaluation of the gastrointestinal actions and the systemic effects of GLP-1–based therapies. A thorough literature search has been carried out on PubMed, Google Scholar, MDPI and other databases, with the inclusion of English language studies from 2016 to 2026. Data from clinical trials, experimental studies and review articles were reviewed to determine the key mechanisms, therapeutic potential, side effects and new applications. GLP-1RAs control glucose homeostasis by stimulating glucose-dependent insulin secretion, inhibiting glucagon, slowing gastric emptying and inducing satiety. Gastrointestinal side effects are common, such as nausea, vomiting, diarrhea, constipation and slowed gastric emptying which could affect adherence to treatment. In addition to metabolic effects, GLP-1-based drugs exhibit hepatoprotective, cardioprotective, renoprotective, anti-inflammatory, and neuroprotective effects. However, additional evidence has emerged that suggests potential applications in metabolic-associated steatohepatitis, cardiovascular disease, neurodegenerative diseases and addiction-related diseases. There are some potential benefits, however, gastrointestinal tolerability, long-term safety, cost, and patient selection are potential problems. In summary, GLP-1-based drugs are a new class of therapeutic agents that have multiple systems of action and use, and their applications go far beyond glycemic control and weight management.