Updated pharmacotherapy guidance from the European Association for the Study of Obesity places greater emphasis on individualized obesity treatment and incorporates new comparative evidence supporting tirzepatide and semaglutide across weight management and liver disease domains. The revised “living” algorithm was presented at the European Congress on Obesity 2026 and simultaneously published in Nature Medicine.
The updated guidance incorporated evidence available through November 21, 2025, including data from 62 randomized controlled trials and six newly eligible primary studies with linked secondary analyses. The recommendations are intended to guide clinicians managing obesity either as a primary treatment target or in combination with obesity-related complications.
Among the most notable revisions, the guidance stated 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.”
The document also expanded recommendations related to metabolic dysfunction-associated steatohepatitis (MASH), a progressive stage of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by liver inflammation and fibrosis that may progress to cirrhosis or liver cancer.
The update incorporated findings from the phase 3 ESSENCE trial evaluating semaglutide in patients with MASH and fibrosis stage F2-F3 without cirrhosis. Based on the currently available evidence, the revised algorithm recommended either semaglutide or tirzepatide for MASH remission, while semaglutide alone was recommended for improvement in liver fibrosis staging because evidence was considered stronger for that indication.
The guidance authors noted that evidence updates across several other obesity-related complications, including type 2 diabetes mellitus, obstructive sleep apnea, osteoarthritis, and cardiovascular outcomes, did not substantially alter prior treatment-domain placements despite the availability of additional data.
The updated recommendations were developed by an international multidisciplinary group led by Andreea Ciudin and Barbara McGowan, together with Volkan Yumuk and colleagues from the EASO Obesity Management Working Group.
“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,” the authors stated.
However, they also cautioned against interpreting the algorithm as a rigid treatment hierarchy.
“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.”
The authors additionally emphasized: “Importantly, the algorithm should not be viewed as a prescribing sequence and should not be read as a universal ranking.”
The guidance was originally launched in October 2025 with the intention of functioning as “living, breathing guidance” that would evolve alongside emerging clinical trial evidence. According to the update, future revisions may incorporate broader patient populations, additional clinically relevant endpoints, newer pharmacotherapies including oral agents, and dedicated safety and tolerability domains alongside efficacy outcomes to better support benefit-risk decision-making in routine clinical care.
