SAFETY PROFILE AND ADVERSE EVENTS ASSOCIATED WITH GLP-1/GIP RECEPTOR AGONISTS IN NON-DIABETIC INDIVIDUALS WITH OVERWEIGHT OR OBESITY: AN INTEGRATIVE REVIEW

Abstract

 Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists constitute a pharmacological class widely used in the treatment of obesity, promoting appetite reduction, increased satiety, and body weight loss. Given the growing use of these medications in non-diabetic individuals, it is important to evaluate their safety profile and the adverse effects associated with treatment. The objective of this study was to identify and characterize the main adverse effects associated with the use of GLP-1 and GIP receptor agonists in non-diabetic individuals with overweight or obesity, compared with placebo or conventional interventions, based on randomized clinical trials published between 2021 and 2025. This study consists of an integrative literature review conducted in the PubMed and Virtual Health Library (VHL) databases. A total of 51 studies were identified, of which 1 was removed due to duplication. After applying the eligibility criteria, 18 articles comprised the final sample. Randomized clinical trials involving non-diabetic individuals with overweight or obesity treated with GLP-1 or GIP/GLP-1 agonists were included. Studies involving diabetic populations, designs other than randomized clinical trials, and studies that did not address the outcomes of interest were excluded. The results demonstrated that GLP-1 and GIP agonists promote significant weight loss, improvement in cardiometabolic parameters, and cardiovascular benefits in specific populations. The most frequently reported adverse effects were gastrointestinal, particularly nausea, vomiting, diarrhea, and constipation, generally classified as mild to moderate. It is concluded that GLP-1 and GIP receptor agonists present a favorable safety profile in non-diabetic individuals with overweight or obesity, with a low occurrence of serious adverse events. Although gastrointestinal effects are common, they were predominantly manageable and did not outweigh the observed clinical benefits, reinforcing the relevance of these drugs as an effective therapeutic strategy for obesity treatment.