Abstract

GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS IN THE MANAGEMENT OF OBESITY AND TYPE 2 DIABETES MELLITUS: A COMPREHENSIVE COMPARATIVE REVIEW OF CLINICAL EVIDENCE

K.V. Shanmukhi Saisree*

Abstract

Background: Glucagon-like peptide-1 receptor agonists (GLP- 1 RAs) represent a transformative pharmacological class simultaneously addressing two major global health burdens: type 2 diabetes mellitus (T2DM) and obesity. This review synthesizes and compares clinical evidence from randomized controlled trials, systematic reviews, meta-analyses, and cardiovascular outcome trials published between 2015 and 2025. Methods: A structured narrative review was conducted drawing on evidence from at least 15 peer-reviewed publications, including landmark trials (LEADER, SUSTAIN- 6, PIONEER-6, REWIND, SELECT, and SURPASS-CVOT) and recent meta-analyses. Outcomes assessed included HbA1c reduction, body weight loss, BMI change, cardiovascular outcomes, and safety profiles. Results: GLP-1 RAs demonstrate clinically meaningful HbA1c reductions ranging from 0.8% to 2.4% and body weight reductions of 1 kg to over 22% across agents and indications. Tirzepatide—a dual GIP/GLP-1 receptor co-agonist—consistently demonstrates the greatest metabolic efficacy. Semaglutide carries the most robust cardiovascular outcome data, including demonstrated superiority in the SELECT trial among non-diabetic obese individuals. Conclusion: The GLP-1 RA class offers individualized, evidence-based therapeutic options for patients with T2DM, obesity, or both. Clinical decision-making should incorporate glycemic burden, degree of obesity, cardiovascular risk, tolerability, and route of administration preference.

Keywords: GLP-1 receptor agonists, semaglutide, liraglutide, tirzepatide, dulaglutide, exenatide, obesity, type 2 diabetes mellitus, HbA1c, cardiovascular outcomes, weight loss.