Obesity, defined by WHO as BMI ≥30 kg/m² in adults, has escalated into a global epidemic, impacting over 1 billion individuals and contributing to 3.7 million deaths in 2024 alone. Projections indicate a doubling of prevalence by 2030, fueling noncommunicable diseases such as cardiovascular conditions, type 2 diabetes, and certain cancers, while exacerbating infectious disease outcomes. Economic burdens are forecasted to reach US$3 trillion annually by 2030. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—including liraglutide, semaglutide, and tirzepatide—have emerged as efficacious pharmacological options, promoting weight loss, glycemic control, and reductions in cardiovascular and renal risks, alongside lowered mortality in diabetes. In September 2025, WHO added select GLP-1 RAs to the Essential Medicines List for high-risk type 2 diabetes management. Responding to Member State requests, this inaugural WHO guideline on GLP-1 RAs for obesity treatment emphasizes their role within a comprehensive, person-centered framework incorporating diet, physical activity, and psychosocial support, aligning with the 2022 Acceleration Plan to Halt the Rise in Obesity.
The guideline was developed through rigorous evidence synthesis from clinical trials, systematic reviews, and meta-analyses, supplemented by extensive consultations with experts, policymakers, and individuals with lived obesity experience. Recommendations were graded using the GRADE approach, balancing benefits against uncertainties in long-term efficacy, safety, and equity. Stakeholder input addressed access barriers, with conditional endorsements reflecting evidence gaps and implementation challenges. The document will be periodically updated as new data emerge.
The guideline conditionally recommends long-term GLP-1 RA use for adults (excluding pregnant individuals) with obesity, based on moderate-certainty evidence of significant weight reduction (5–15% body weight) and metabolic improvements. Intensive behavioral interventions (e.g., structured diet and exercise programs) are suggested as adjuncts, supported by low-certainty evidence of enhanced outcomes. Contraindications include pregnancy, with monitoring required for gastrointestinal side effects and rare risks like pancreatitis. Equity analyses highlight disparities: high costs and supply shortages could limit access to <10% of eligible individuals by 2030, exacerbating inequalities in low- and middle-income countries. Safety concerns encompass substandard/falsified products, necessitating regulated distribution and prescriber oversight. Implementation pillars include population-level policies for healthier environments, targeted screening for at-risk groups, and lifelong care models.
GLP-1 RAs represent a breakthrough in obesity pharmacotherapy, potentially aiding millions in mitigating disease burdens, yet their success hinges on multisectoral action for affordability and readiness. WHO urges governments to adopt pooled procurement, tiered pricing, and voluntary licensing to expand manufacturing and ensure quality. A 2026 prioritization framework will target highest-need populations first. Medications alone are insufficient; integrated strategies are essential to foster sustainable, equitable obesity control globally.
