Incretin Analogues for Weight Reduction in Non-Diabetic Obese: A Review of Liraglutide, Semaglutide, and Tirzepatide Beyond Glycemic Control

Obesity is a complex, multifactorial disease that contributes to a broad range of cardiometabolic, reproductive, and psychological disorders. Representing a major global health challenge, obesity can be addressed by lifestyle modifications such as reduced calorie intake, physical activity, adequate sleep, and stress management to help achieve sustainable weight loss and improve metabolic health in the long term. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two naturally produced incretin hormones in the gastrointestinal tract. Incretin analogues were initially approved for type 2 diabetes mellitus but were later found to exhibit weight-reducing properties. Liraglutide, semaglutide, and tirzepatide are the three incretin analogues approved for obesity in non-diabetic patients. This narrative review presents detailed comparisons of the three approved incretin analogues for obesity, their cost-effectiveness, and trends in the clinical setting.