Annual review of physiologyOct 23, 2026

New Developments in Treatments Using Incretin Hormones

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 24, 2026

Abstract

Next-generation therapies are being developed to enhance the effectiveness of obesity treatment, addressing challenges such as reduced efficacy and high costs.

GLP-1-based therapies have significantly improved obesity treatment but face challenges in diabetic populations.
Adverse gastrointestinal effects and high costs contribute to lower adherence in real-world settings.
Emerging therapies include receptor polyagonists, oral formulations, and small-molecule incretin mimetics aimed at improving treatment outcomes.
Weight regain after stopping treatment is a critical issue that needs to be addressed.
Sustained lifestyle interventions and muscle mass preservation may play a role in stabilizing weight.
Research is focusing on biological factors that may contribute to weight regain, including changes in brain regulation, metabolism, and fat tissue structure.

Simplified

Glucagon-like peptide-1 (GLP-1)-based therapies marked a major breakthrough in obesity pharmacotherapy, while subsequent advancements targeting multiple entero-pancreatic hormones now deliver weight loss previously achievable only with bariatric surgery, alongside improvements in obesity-related complications. Despite this progress, significant challenges persist, including reduced efficacy in diabetic populations, gastrointestinal adverse effects, and high costs that drive a real-world adherence gap. Consequently, next-generation therapies, including receptor polyagonists, oral formulations, and small-molecule incretin mimetics with optimized pharmacokinetic profiles, are being developed to enhance efficacy, tolerability, and accessibility while maintaining safety. However, weight regain after treatment cessation remains a critical hurdle. Growing evidence underscores the importance of sustained lifestyle interventions and muscle mass preservation to facilitate weight stabilization. Concurrently, research is heavily focused on identifying the biological drivers of weight regain, such as altered neuroregulation, metabolic adaptation, and adipose tissue remodeling. This review examines the current landscape, limitations, and emerging strategies of obesity pharmacotherapy.

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New Developments in Treatments Using Incretin Hormones

Abstract

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