Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in the Management of Diabetes Mellitus: A Review

Abstract

In particular, type 2 diabetes mellitus (T2DM) is a fast growing global health concern associated with high rates of morbidity, mortality, and financial burden. Despite the availability of various pharmacological treatments, the long-term management of type 2 diabetes remains challenging due to weight gain, hypoglycemia, increasing β-cell dysfunction, and the limited cardiovascular benefits of standard therapy. The introduction of incretin-based drugs, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is a significant advancement in the treatment of diabetes. GLP-1, an endogenous incretin hormone secreted by intestinal L-cells, inhibits the release of glucagon, postpones stomach emptying, promotes satiety, and increases glucose-dependent insulin production. Native GLP-1 is rapidly broken down by dipeptidyl peptidase-4 (DPP-4), whereas synthetic GLP-1 RAs are made to resist this breakdown and preserve glycemic control.

A. GLP-1 RAs effectively demonstrate a low risk of hypoglycemia, promote significant weight loss, and reduce glycated hemoglobin (HbA1c) by 0.8–1.5%, according to clinical research. Several important cardiovascular outcome trials, such as LEADER (liraglutide), SUSTAIN-6 (semaglutide), and REWIND (dulaglutide), have shown reductions in major adverse cardiovascular events and renal protection in addition to lowering blood sugar, establishing GLP-1 RAs as disease-modifying medications. Recent developments that have improved patient acceptance and adherence include oral semaglutide and once-weekly formulations. While tirzepatide and other next-generation dual and triple incretin agonists show promise for improved metabolic outcomes, future research focuses on expanding its use beyond diabetes to include obesity, non-alcoholic steatohepatitis, and neurodegenerative diseases. Long-term safety, stomach intolerance, and high cost are still problems and accessibility in resource-constrained settings. Lastly, GLP-1 receptor agonists represent a paradigm shift in the management of type 2 diabetes by providing numerous benefits that go well beyond glucose control. The therapeutic value of multi-agonist therapy is expected to rise over the next 10 years due to greater research in precision medicine and novel delivery technologies.