Efficacy and Safety of GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus: A Systematic Literature Review

Abstract

Type 2 diabetes mellitus remains a global health challenge, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a prominent therapeutic class with pleiotropic effects beyond glycemic control. This systematic literature review was conducted to comprehensively evaluate the efficacy and safety of GLP-1 RAs in adults with type 2 diabetes, with a particular focus on glycemic control, weight management, cardiovascular outcomes, renal protection, and tolerability profiles. We systematically searched major electronic databases for randomized controlled trials, observational studies, and meta-analyses published up to the present date, without language restrictions. Studies were selected based on predefined inclusion criteria, and data extraction and quality assessment were performed independently by two reviewers. The synthesis of evidence revealed that GLP-1 RAs consistently achieve significant reductions in glycated hemoglobin and body weight compared to placebo and several active comparators. Cardiovascular benefits were demonstrated across multiple agents, with reductions in major adverse cardiovascular events and all-cause mortality observed in patients with established cardiovascular disease. Renal outcomes also favored GLP-1 RA therapy, showing a reduction in the progression of albuminuria and preservation of estimated glomerular filtration rate. Gastrointestinal adverse events, particularly nausea and vomiting, were the most commonly reported side effects, though these were generally transient and manageable. Comparative analyses suggested that GLP-1 RAs may offer advantages over dipeptidyl peptidase-4 inhibitors and insulin in terms of weight loss and hypoglycemia risk, while their efficacy relative to sodium-glucose cotransporter-2 inhibitors appeared context-dependent. Emerging dual and triple agonists, as well as oral formulations, showed promise in early trials. Real-world evidence further supported favorable adherence and patient satisfaction. We conclude that GLP-1 receptor agonists represent a highly effective and generally safe therapeutic option for type 2 diabetes, with important cardiorenal protective effects that extend beyond glucose lowering