EASO issues new update of its ‘living’ guidance for appropriate use of pharmacotherapy in obesity management

The first update to guidance on pharmacological management of obesity and its complications, issued by the European Association for the Study of Obesity (EASO) and published in Nature Medicine, adds new evidence from multiple randomised clinical trials. The updated ‘algorithm’ is presented at this year’s European Congress on Obesity in Istanbul, Turkey (12-15 May).

Among the highlights of this updated algorithm are that, where weight loss is the main goal in people living with obesity without complications, the evidence is now stronger for tirzepatide compared to semaglutide and other options. There is also updated evidence on liver disease, related to metabolic dysfunction-associated steatotic liver disease (MASH) remission and semaglutide for improvement in liver fibrosis.

The authors of this updated evidence are an international team of obesity experts led by the co-chairs of the EASO Obesity Management Working Group who are Professor Andreea Ciudin, Vall d’Hebron University Hospital, Autonomous University Barcelona, Barcelona, Spain and Professor Barbara McGowan, Guys & St Thomas‘s Hospital NHS Foundation Trust, London, UK; and a multidisciplinary team including EASO President Professor Volkan Yumuk, Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty, Istanbul, Turkey, and colleagues.

EASO decided to launch an algorithm specifically dedicated to pharmacological management of obesity to provide guidance for healthcare providers across Europe considering offering pharmacological options to their patients, whether their target was weight loss alone, or combined with management of one or more obesity-related complications. 

The first version of the guidance was published in October 2025, and EASO committed then that it would be ‘living, breathing guidance’, updated with fresh evidence from clinical trials as often as is reasonably possible, most likely on an annual basis.

This new update incorporates evidence up to 21 November 2025, with 62 randomised controlled trials (RCTs) contributing to the meta-analysis, including six newly eligible primary studies plus linked or secondary publications providing additional data.

The authors say: “As the evidence base has expanded, the relative separation between the two most effective weight-lowering medications — tirzepatide and semaglutide — has become clearer. This is consistent with recent head-to-head evidence that provides a direct clinical comparison between tirzepatide and semaglutide – the SURMOUNT-5 trial presented at last year’s European Congress on Obesity in Malaga, and published in NEJM.”

But they add: “Although head-to-head evidence is emerging, many comparisons between treatments remain based on results from separate RCTs rather than direct comparisons. The updated algorithm therefore reflects the best available comparative evidence, with the recognition that treatment decisions must also consider clinical judgement, individual patient characteristics and preferences.”

And they emphasise: “Importantly, the algorithm should not be viewed as a prescribing sequence and should not be read as a universal ranking.”

The most substantive change for complications of obesity in the updated algorithm is for management of metabolic dysfunction-associated steatohepatitis (MASH) in people living with obesity. MASH is a progressive stage of metabolic dysfunction-associated steatotic liver disease (MASLD) where there is inflammation and liver fibrosis, in addition to increased liver fat content, that can lead to liver cirrhosis and/or liver cancer. The phase 3 ESSENCE trial of semaglutide in MASH with fibrosis stage F2–F3 without cirrhosis has now reported, providing evidence on both resolution of steatohepatitis and changes in liver fibrosis stage. Thus the updated algorithm now recommends either semaglutide or tirzepatide for MASH remission, but only semaglutide for improvement of liver fibrosis staging, as the evidence is currently stronger for semaglutide for this indication.

On evidence for other complications of obesity, the authors explain: “Beyond total body weight loss and liver outcomes, few non- liver domains in the guidance such as remission of Type 2 diabetes, obstructive sleep apnoea, osteoarthritis and cardiovascular outcomes are materially altered by the evidence update.  Some new or linked data exist, but they did not substantially change most complication-domain placements.” (See figure in full paper for detail for other complications)

The authors conclude: “Future updates may incorporate evolving standards in the definition and management of obesity, broader patient populations and geographic settings, new pharmacotherapies and formulations (including oral agents), and additional clinically relevant endpoints as the evidence base develops. Future updates will consider incorporating a dedicated safety and tolerability domain (for example, discontinuation rates or adverse events), alongside efficacy, to better reflect benefit-risk decision-making in routine care.”