Current clinical application of incretin therapy for obesity management.

Canadian journal of physiology and pharmacology2026PMID: 41420876

View on PubMed DOI: 10.1139/cjpp-2025-0152

Plain Language Summary

Review synthesizing current clinical evidence on incretin therapy for obesity management, covering liraglutide, semaglutide, and tirzepatide's mechanisms (appetite suppression via incretin hormone pathway modulation), weight loss efficacy data from SCALE, STEP, and SURMOUNT trials, and the paradigm shift toward pharmacological obesity intervention. Positions tirzepatide as the most effective current pharmacological obesity option. Provides clinicians with an accessible clinical synthesis of incretin obesity therapy—establishing the evidence hierarchy from liraglutide through tirzepatide for prescribers implementing pharmacological obesity management in routine practice.

Abstract

Incretin therapy, utilizing glucagon-like peptide-1 (GLP-1) receptor agonists and dual receptor agonists, is a cornerstone of obesity management due to effects on appetite suppression, weight loss, and metabolic improvement. Liraglutide, semaglutide, and tirzepatide promote weight reduction by modulating incretin hormone pathways, leading to decreased caloric intake. Recent studies with semaglutide and tirzepatide have demonstrated substantial weight loss outcomes beyond glucose-lowering benefits, shifting the paradigm of obesity treatment toward pharmacological interventions. While effective in weight loss, challenges remain regarding long-term efficacy, tolerability, and accessibility. Future directions include optimizing combination therapies and exploring novel incretin-based molecules with dual or triple receptor activity. This review focuses on the clinical application of incretin therapy in obesity, emphasizing practical considerations and highlighting therapeutic benefits for obesity to improve outcomes and public health.

Authors

Skinner, Karlie; Clements, Jennifer N

Keywords

GIPGLP-1incretinobesitypharmacotherapy