The Long-term Safety of Glucagon-Like Peptide-1 Receptor Agonists and Glucose-Dependent Insulinotropic Peptide Receptor Agonists for Obese Patients Without Diabetes: A Systematic Literature Review and Meta Analysis

Author(s)

Anwesha A. Kandhare, Master in Pharmacology, Somasundaram S, Pharm.D, Santosh Kumar, MA.
SIRO Clinpharm Private limited, Mumbai, India.
OBJECTIVES: The purpose of our research was to evaluate the long-term effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic peptide receptor agonists (GIP-RA) and the occurrence of side effects in the obese and non type 2 diabetes (non-T2D) groups separately.
METHODS: We performed an electronic search on Medline, Embase, Web of Science, Scopus, ClinicalTrials.gov, and Cochrane Central using keywords such as “GLP-1 RA”, “GIP RA”, “obesity”, “overweight”, and “weight loss". For the inclusion, we considered global GLP-1 RAs and GIP RA available A part of our analysis was paying attention to the long-term safety effect. We also presented the results as a random-effects meta-analysis with the mean difference (MD), odds ratio, standardized mean difference (SMD), and relative risk.
RESULTS: A total of 47 articles were included in our research analysis. Although the GLP-1 RA- and GIP-RA-based therapies were found to be associated with a significantly lower risk of all-cause mortality however, several cardiovascular complications, such as a lower rate of ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke, and atrial fibrillation were markedly visible in those patients. GLP-1 RA and GIP-RAs also revealed a protective effect against acute kidney injury and allergic reactions. These protective effects were uniform across a variety of subgroups and regions. However, there is a significant association of gastrointestinal disorders observed by GLP-1 in different studies.
CONCLUSIONS: We found that GLP-1 RAs and GIP-RAs might be a complete approach towards the treatment of obesity however, long-term use of those drugs can lead to pancreatitis, gastrointestinal issues, kidney problems, and other serious side effects that require careful healthcare monitoring

Conference/Value in Health Info

2025-09, ISPOR Real-World Evidence Summit 2025, Tokyo, Japan

Value in Health Regional, Volume 49S (September 2025)

Code

RWD189

Topic Subcategory

Distributed Data & Research Networks

Disease

SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity)

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