The World Health Organization has released its first guideline specifically addressing the use and indications of glucagon-like peptide-1 (GLP-1) therapies for treating obesity in adults. The document issues two conditional recommendations that highlight both the therapeutic potential and the substantial implementation, equity, and feasibility challenges that accompany this drug class. Two accompanying Good-Practice Statements emphasize that obesity is a chronic, relapsing disease requiring lifelong, person-centered care, early diagnosis, management of complications, and context-appropriate lifestyle counseling as foundational steps before considering structured behavioral interventions.
WHO states that GLP-1 therapies may be used as long-term treatment—defined as continuous therapy for at least 6 months—for adults living with obesity. This recommendation is conditional, supported by moderate-certainty evidence, and shaped by considerations of cost, feasibility, equity, system readiness, and variability in patient values and preferences.
A second conditional recommendation notes that adults prescribed GLP-1 therapies may receive intensive behavioral therapy (IBT) as part of a comprehensive, clinical algorithm. IBT comprises structured goal-setting for dietary change and physical activity, energy-intake restriction, weekly counseling, and routine progress monitoring. WHO emphasizes that all individuals, including those starting GLP-1 therapies, should first receive foundational behavioral and lifestyle counseling before progressing to IBT.
Both recommendations reflect separate systematic reviews of liraglutide, semaglutide, and tirzepatide. The guideline development group (GDG) elected to treat GLP-1 therapies as a class for the purpose of recommendation-making. The GDG cited limited long-term data on efficacy, safety, titration, maintenance, and discontinuation; major cost and supply constraints; context-specific feasibility; and health-equity implications as key drivers of the conditional grading.
Obesity as a Global Crisis
The guideline situates obesity as a lifelong, relapsing condition affecting more than 1 billion people worldwide. In 2024, obesity contributed to an estimated 3.7 million deaths from noncommunicable diseases—12% of global noncommunicable disease mortality. Economic projections estimate annual global costs reaching $3 trillion by 2030, with countries facing 30% prevalence potentially allocating up to 18% of national health expenditure to obesity-related care.
Evolution of GLP-1 Therapies
Initially approved in 2005 for type 2 diabetes, GLP-1 therapies subsequently gained approval for chronic weight management after evidence demonstrated their effects on appetite regulation and satiety. As of October 2025, 12 GLP-1 agents are approved for diabetes and/or obesity indications, and more than 40—including multireceptor agonists—are in development. While trials have explored broader potential benefits across cardiovascular, metabolic, and neurologic conditions, WHO notes that these investigational indications lie outside the scope of its recommendations.
The Supply Challenge
A major barrier identified by the guideline is global production capacity. Even under optimistic projections, current manufacturing output could reach only about 100 million people—fewer than 10% of those living with obesity worldwide. The GDG highlighted the need for multisector collaboration, expanded generic manufacturing capacity, and potentially a WHO prequalification pathway as the semaglutide patent approaches expiration in 2026.
GLP-1 therapies have been added to the WHO Model List of Essential Medicines for a specific high-risk subgroup: adults living with obesity, type 2 diabetes, and established cardiovascular or kidney disease. This inclusion pertains to primary-care use and reflects GDG deliberations on feasibility, access, and population need.
Implementation Roadmap
WHO states that effective implementation will require significant health-system strengthening, including workforce training; the development of patient registries and referral pathways; investment in procurement and cold-chain systems; and robust monitoring frameworks. Digital tools and telehealth may support adherence and follow-up, while person-centered, nondiscriminatory care remains a core principle across all settings.
Because near-term supply and system capacity remain limited, WHO identifies an urgent need for a transparent and equitable prioritization framework to identify those at highest need. The GDG will reconvene in early 2026 to develop risk-stratification tools, support Member States in cost-effectiveness analyses, and review emerging evidence on discontinuation, titration, maintenance strategies, and multimodal algorithm components (including therapeutic nutrition and surgical options).
WHO stresses that medication alone—even with expanded global access—cannot counter the rising global obesity burden. GLP-1 therapies must be embedded within an integrated ecosystem that includes population-level prevention strategies, upstream approaches addressing social and environmental determinants, and comprehensive management of comorbidities.
A Turning Point for Global Obesity Care
WHO’s publication marks a foundational step toward building a fair, coordinated obesity-care ecosystem. The organization calls for global collaboration to ensure that prevention, treatment, and long-term management services become universally available, accessible, affordable, and sustainable, translating pharmacologic innovation into meaningful population-level impact.
Disclosures are available in the published Special Communication.
Source: JAMA
