World Health Organization Issues Guideline for Glucagon-like-Peptide-1 Therapies Use in Obesity: JAMA December 2025 Special Communication

This special communication is published in Journal of the American Medical Association in December 2025.

A Global Framework for Obesity Management

Obesity is recognized by the WHO as a complex, chronic, and relapsing disease. Affecting more than 1 billion people worldwide, it is rising in prevalence across nearly all nations. In 2024 alone, obesity contributed to 3.7 million deaths linked to non-communicable diseases. GLP-1 therapies, originally developed for diabetes, have rapidly become transformative in obesity treatment due to their ability to reduce appetite, enhance satiety, and achieve clinically meaningful weight loss.

The rise of obesity reflects a combination of global food system changes, sedentary lifestyles, socioeconomic inequalities, and environmental determinants. WHO emphasizes that obesity management must extend far beyond weight reduction, recognizing the condition as a lifelong disease requiring sustained and integrated care.

GLP-1 Therapies: A New Era in Obesity Treatment

GLP-1 therapies have emerged as a significant innovation by targeting biological pathways that regulate energy intake and appetite. Beyond weight loss, these agents have shown benefits in reducing cardiovascular events, preventing diabetes, improving heart failure outcomes, and supporting kidney health. Their arrival has created a pivotal moment in the management of global obesity.

Guideline Development: A Rigorous, Evidence-Based WHO Process

In response to requests from Member States, the WHO developed the new guideline through a transparent and systematic approach. The process was based on the GRADE methodology, with contributions from a multidisciplinary Guideline Development Group (GDG) involving experts in epidemiology, pharmacology, health policy, economics, and clinical management.

Three systematic reviews informed the guidance, focusing on liraglutide, semaglutide, and tirzepatide. While the evidence for each agent was reviewed, the GDG ultimately chose to consider GLP-1 therapies collectively as a class due to shared mechanisms and similar outcomes.

The Two Core Recommendations from WHO

The guideline offers two primary recommendations.

The first states that GLP-1 therapies may be used as long-term treatment for adults living with obesity, with “long-term” intended as continuous use for six months or longer as per current regulatory definitions.

The second recommendation suggests that adults prescribed GLP-1 therapies may also be provided Intensive Behavioral Therapy (IBT) as part of a comprehensive multimodal clinical algorithm. IBT is defined as including structured goal setting for physical exercise and diet, energy intake restriction, weekly counseling, and routine progress assessments, which can amplify and sustain medication benefits.

Both recommendations are graded as conditional. While GLP-1 therapies demonstrate clear effectiveness, conditionality reflects concerns about limited long-term safety data, high treatment costs, inequitable global access, and inadequate readiness of health systems to support widespread use.

The guidelines acknowledge that GLP-1 therapies offer benefits beyond weight reduction. Evidence now supports their use in reducing major cardiovascular events, improving heart failure with preserved ejection fraction (HFpEF), preventing diabetes progression, and supporting kidney health. These expanding indications underscore the broad cardiometabolic significance of GLP-1–based therapy.

The Global Challenge Ahead: Building a Sustainable Obesity Ecosystem

The guideline serves as a call to action for policymakers, health systems, and global stakeholders. Tackling obesity requires shifting from isolated risk-factor management to a chronic disease model that integrates behavioral therapy, medication, and preventive public health strategies. The advent of GLP-1 therapies represents a turning point, but their success ultimately depends on building a fair, sustainable, and inclusive global obesity ecosystem.

Clinical & Stakeholder Importance: Transforming Systems for Equitable, Effective Obesity Care

From a clinical perspective, GLP-1 therapies provide powerful pharmacologic support, but their impact depends on system-wide readiness. With current global production capacity sufficient for only about 100 million people—less than 10% of those with obesity—scaling access remains a major challenge. Effective implementation requires trained healthcare workforces, integrated primary care platforms, and nondiscriminatory care pathways that prioritize prevention and long-term disease management.

Reference: Celletti F, Farrar J, De Regil L. World Health Organization Guideline on the Use and Indications of Glucagon-Like Peptide-1 Therapies for the Treatment of Obesity in Adults. JAMA. Published online December 01, 2025. doi:10.1001/jama.2025.24288