Safety profile of glucagon-like peptide-1 agonists (GLP1) for weight loss, a scoping review

Objective: To assess the safety profile of GLP-1 receptor agonists for weight loss, with a focus on adverse events and their use in special subpopulations. Methods: A systematic scoping review was conducted, following PRISMA-ScR guidelines. The PubMed Database and the Cochrane Central Register of Controlled Trials were searched, using predefined terms. Studies were selected based on eligibility criteria including being human-focused, peer-reviewed publications, reporting on studies containing data on adverse events potentially induced by liraglutide or semaglutide or details of their safety profile, with no restrictions on study type or year of publication. Results: Out of 5729 studies identified, 303 met the inclusion criteria. Studies investigated liraglutide and semaglutide use for weight loss as primary or as secondary outcome in use for type 2 diabetes or other diseases. Multiple adverse events were identified, such as gastrointestinal adverse events, injection-site reactions, cardiac-related events, gallbladder and biliary diseases, pancreatitis, cancer, diabetic retinopathy events, psychiatric disorders, hypoglycemia and kidney events. GLP-1 receptor agonist use was investigated in patients with chronic kidney disease, heart disease, liver impairment, type 1 diabetes, metabolic or endocrine diseases and in pregnant women or patients who have undergone solid organ transplantation. Discussion: Findings indicate that GLP-1 receptor agonists are generally well-tolerated across different age subpopulations, including adolescents, adults and elderly, with gastrointestinal adverse events and especially nausea being the most frequent and the main reason for treatment discontinuation. Other adverse events include injection-site reactions, heart rate increase, cholelithiasis and cholecystitis, while hypoglycemic and acute kidney events were rare. Serious adverse events, such as pancreatitis, medullary thyroid carcinoma, progression of diabetic retinopathy or psychiatric disturbances raised significant concerns, even though the existence of an actual cause-effect relationship remains unclear. Specific concerns arose in populations with advanced chronic kidney disease and severe heart failure, highlighting the need for cautious use and tailored monitoring in these groups. GLP-1 receptor agonist use is avoided in patients with type 1 diabetes, end-stage renal disease, history of pancreatitis or MEN2, family or personal history of medullary thyroid carcinoma, in post-transplant individuals, in pregnant or breastfeeding women and in young children under 10-12 years old. Conclusion: GLP-1 receptor agonists, particularly liraglutide and semaglutide, are an indispensable tool in the fight against obesity, showing efficacy and safety in various populations. However, high rates of gastrointestinal adverse events may reduce adherence, particularly in elderly or frail individuals. Their use requires careful consideration and personalization, especially in specific vulnerable subgroups. Future research is needed in order to address gaps in evidence, ensuring these therapies are used effectively and with minimal risks.