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Adverse Events Associated with Incretin-Based Therapies: A Narrative Review on Mechanisms, Clinical Management, and
Mansour Tobaiqy1, Sulafa Tarek Alqutub2
1Department of Basic Medical Sciences, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia.
Drug Design, Development and Therapy
|August 3, 2026
Summary
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively treat obesity and type 2 diabetes. While generally safe, gastrointestinal issues are common, and careful patient monitoring is crucial for optimizing GLP-1RA therapy.
Area of Science:
- Pharmacology and Therapeutics
- Endocrinology
- Clinical Safety Research
Background:
- Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established treatments for obesity and type 2 diabetes mellitus (T2DM).
- These therapies offer significant benefits including weight reduction, glycemic control, and cardiovascular/renal protection.
- However, safety concerns associated with GLP-1RAs impact treatment adherence, patient acceptance, and clinical decision-making.
Purpose of the Study:
- To comprehensively review the safety profiles of GLP-1RAs used for obesity and T2DM.
- To evaluate common and emerging adverse events using clinical, mechanistic, and pharmacovigilance data.
- To inform clinical practice regarding the safe and effective use of GLP-1RAs.
Main Methods:
- A narrative review synthesizing evidence from 60 studies and safety reports.
- Searches were conducted in PubMed/MEDLINE, Embase, and Web of Science (January 2005–April 2026).
- Inclusion of data from randomized controlled trials, observational studies, meta-analyses, pharmacovigilance investigations, and regulatory reports.
Main Results:
- Predominantly gastrointestinal adverse events (nausea, vomiting, diarrhea, constipation) were most common and led to treatment discontinuation.
- Infrequent concerns included renal events, gallbladder complications, and rare cases of acute pancreatitis.
- Emerging signals identified through observational data include retinopathy worsening, muscle mass reduction, psychiatric symptoms, and alopecia.
Conclusions:
- GLP-1RA adverse events are largely predictable pharmacological effects, varying by agent, dose, and patient factors.
- Risk-stratified prescribing is essential, considering patient vulnerabilities like gastrointestinal tolerance, renal status, and frailty.
- Continued surveillance is necessary to define rare/emerging safety signals and optimize GLP-1RA use across diverse populations.
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