Anca-Elena Craciun 1, Camelia Larisa Vonica 2 *, Adriana Rusu 1
1 Medical Sciences, 2nd Department, Faculty of Nursing and Health Sciences, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
2 Department of Diabetes and Nutrition Diseases, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
* Correspondence to: Camelia Larisa Vonica, Department of Diabetes and Nutrition Diseases, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 2–4 Clinicilor Street, Cluj-Napoca, 400006, Romania. Phone: +40264296829; E-mail: camelia.sulea@umfcluj.ro
Abstract
Obesity is a global public health challenge affecting more than half of the world’s population. It is associated with increased morbidity, mortality, and healthcare costs. While metabolic surgery has historically provided the most effective long-term weight loss, recent advances in incretin-based pharmacotherapy have transformed non-surgical obesity management. Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have demonstrated good efficacy in inducing clinically significant weight loss. This review summarizes the evidence on semaglutide and tirzepatide, the two most widely used incretin-based therapies. Both drugs promote weight loss through delayed gastric emptying and central appetite regulation. Semaglutide 2.4 mg has been shown in the STEP clinical trial program to induce average weight losses of 10–18% across diverse populations. Tirzepatide, evaluated in the SURMOUNT program, demonstrated superior efficacy, achieving mean weight reductions of 20–25%. Beyond weight reduction, incretin-based therapies significantly improve body composition. Weight loss is primarily driven by reductions in fat mass, including visceral adiposity, with proportional losses of lean mass. Available evidence indicates preservation of muscle quality and physical function despite reductions in lean mass. Semaglutide and tirzepatide represent a major advancement in obesity treatment. Their efficacy, safety, and metabolic benefits support their role as long-term, disease-modifying therapies in obesity management.