The European Association for the Study of Obesity released a new framework for pharmacologic obesity treatment that identified semaglutide and tirzepatide as first-line therapies for weight management and complication control.
The algorithm, based on randomized controlled trials published through January 31, 2025, aligned medication selection with patient characteristics and outcomes.
In weight reduction trials, tirzepatide reduced body weight by 16.5% at endpoint, while semaglutide reduced weight by nearly 9%. At 52 weeks, reductions were about 15% and 11%, respectively. Phentermine–topiramate produced almost a 9% loss in weight, while naltrexone–bupropion, liraglutide, and orlistat produced smaller effects of approximately 5%, 4%, and 3%.
Tirzepatide improved obstructive sleep apnea in the only dedicated randomized trial. Semaglutide reduced knee pain in osteoarthritis more effectively compared with liraglutide. In type 2 diabetes, remission rates were highest with tirzepatide and semaglutide, whereas liraglutide and naltrexone–bupropion showed smaller effects. In cardiovascular disease, semaglutide reduced major adverse cardiovascular events, while naltrexone–bupropion showed no benefit. Both tirzepatide and semaglutide reduced hospitalizations in patients with heart failure; however the data didn't allow separation by preserved vs reduced ejection fraction. Tirzepatide improved remission of steatohepatitis and fibrosis in patients with metabolic dysfunction–associated steatohepatitis, while semaglutide reduced liver fat without significant histologic changes at the time of analysis.
The framework was developed through systematic review and network meta-analysis of randomized controlled trials. Investigators evaluated medications by weight-loss efficacy, effects on obesity-related complications, and safety. Complications were categorized as “fat mass disease,” associated with mechanical strain, and “sick fat disease,” involving metabolic and inflammatory dysfunction.
“Tailoring treatment to the individual is a complex task that must consider several factors, including the severity of adiposity, the presence and extent of complications, comorbidities, and concurrent therapies. Socioeconomic context, patient values, expectations, and personal goals must also be considered,” wrote lead study author Barbara McGowan, MD, of the Department of Endocrinology and Diabetes at Guy’s and St Thomas’ National Health Service Trust, London, UK.
Evidence was limited in patients with a body mass index (BMI) above 40 kg/m² and absent in those with a BMI below 27 kg/m². Few medications were directly tested for each complication, so some benefits may be attributable to weight loss rather than drug-specific effects. Long-term safety data were inconsistent, with cardiovascular safety reported only for semaglutide and naltrexone–bupropion. Evidence was insufficient for rare adverse events.
The The European Association for the Study of Obesity (EASO) framework provided guidance for selecting obesity medications according to patient needs and complication profiles. The investigators emphasized that treatment algorithms should support, not replace, clinical judgment and should be updated as new evidence becomes available.
Several of the study authors reported consulting fees, speaker honoraria, or research funding from pharmaceutical companies, including Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Pfizer, and others. Some of the study authors reported no conflicts of interest.
Source: Nature Medicine