- The WHO issued new guidelines endorsing GLP-1 receptor agonists for the long-term treatment of obesity in adults.
- GLP-1 drugs must be combined with counseling on behavioral and lifestyle changes, the WHO emphasized.
- Widespread, equitable, and affordable access to GLP-1 agents remains a top priority.
GLP-1 receptor agonists for obesity are effective over the long term when paired with lifestyle interventions, but global accessibility must be improved, the World Health Organization (WHO) concluded.
The WHO made two recommendations in its first-ever guideline on GLP-1 agents: The drugs can be used as a long-term (6 months or longer) obesity treatment, based on moderate-certainty evidence, and patients prescribed these agents should receive counseling on behavioral and lifestyle changes, including diet and exercise, based on low-certainty evidence.
The recommended use of GLP-1 therapies, including tirzepatide (Zepbound), semaglutide (Wegovy), and liraglutide (Saxenda), for adults with obesity is "grounded in the recognition of obesity as a chronic, relapsing disease that requires lifelong care," wrote Francesca Celletti, MD, PhD, of the WHO, and colleagues in JAMA.
GLP-1 agonists are "more than a scientific breakthrough," the authors noted. "They represent a new chapter in the gradual conceptual shift in how society approaches obesity -- from a 'lifestyle condition' to a complex, preventable, and treatable chronic disease. This promise of effective treatment can catalyze the broader transformation needed to build an integrated ecosystem that redefines health promotion, disease prevention, and care with a focus on equity."
That being said, they don't replace the need for a healthy diet and physical activity, emphasized WHO Director-General Tedros Adhanom Ghebreyesus, PhD, during a press conference.
"These new medicines are powerful clinical tools offering hope to millions. But let me be clear: medicine alone will not solve the obesity crisis," he said. "Obesity is a complex disease that ... has many social, commercial, and environmental determinants requiring action in many sectors -- not only in the clinic."
"One of the most serious public health challenges of our time," according to Ghebreyesus, obesity affects over 1 billion people worldwide. Last year, there were 3.7 million deaths related to obesity, accounting for 12% of all deaths due to noncommunicable diseases globally.
By 2030, the number of people living with obesity is expected to double to 2 billion globally.
GLP-1 receptor agonists have been FDA approved for over 20 years for type 2 diabetes, and were added to WHO's list of essential medicines for the treatment of diabetes in high-risk groups this past September.
More recently, semaglutide and tirzepatide showed significant weight loss among patients with obesity, leading to FDA approvals for this indication in 2021 and 2023.
Despite their efficacy, there are several barriers to widespread use of GLP-1 drugs, including steep costs, a limited production capacity, and supply-chain constraints. The WHO said implementation of its recommendations rely on three critical factors:
- Achievement of more widespread and fair access to affordable GLP-1 therapies
- Readiness of health systems to deliver high-quality obesity care that integrates GLP-1 drugs with behavioral therapy
- Care that is person-centered, nondiscriminatory, and oriented toward universal access
"Our greatest concern is equitable access," said Ghebreyesus.
Even under the current best projected scenario, production of GLP-1 drugs would only cover around 100 million people -- less than 10% of the worldwide obesity population.
"Without concerted action, these medicines could contribute to widening the gap between the rich and the poor, both between and within countries," said Ghebreyesus. Strategies to improve access include generic production (particularly as the patent for semaglutide expires next year), pooled procurement, tiered pricing, voluntary licensing, and development of more oral formulations, which may help to simplify production, logistics, and storage.
"This guideline is a key part of WHO's acceleration plan to stop obesity," Ghebreyesus added. "It is built on evidence and shaped by the principle of health for all, ensuring that scientific progress benefits everyone, everywhere."
Both recommendations in the guideline are listed as conditional, meaning that the benefits don't clearly outweigh the undesirable outcomes from an individual patient, clinical, and public health perspective.
Celletti and colleagues called out the limited data on long-term efficacy and safety, titration, maintenance, and discontinuation of GLP-1 drugs. When benefits are weighed against the high price tag of most agents, inadequate health system preparedness, and potential equity implications, the scale could be tipped unfavorably, they noted.
There is also low certainty of evidence that intensive behavioral therapy can enhance the weight-loss effects of GLP-1 drugs. Conditionality was also attributed to the variability in patient priorities, potential health equity impacts, and context-specific feasibility, in addition to delivery costs.
The recommendations only apply to adults with obesity, defined as a body mass index of 30 or higher. The guidelines do not mention adults living with overweight and obesity-related comorbidities, for whom GLP-1 agents are also indicated.
This is a "living" guideline, meaning it will be updated as more data become available, the authors said. Guidelines on use of GLP-1 drugs in children with obesity are expected soon.
Disclosures
Celletti reported no disclosures. A co-author reported receiving grants from the Gates Foundation, which provided partial financial support for the development of the guideline.
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