On May 13, at the 33rd European Congress on Obesity in Istanbul, Türkiye, findings from the Phase III SURMOUNT-MAINTAIN trial (NCT06047548) were presented, evaluating the use of Eli Lilly’s Zepbound (tirzepatide) in sustaining weight loss following an initial 60-week open-label weight-loss period. SURMOUNT-MAINTAIN assessed whether weight reduction achieved with tirzepatide at its maximum tolerated dose (MTD; 10mg or 15mg) could be sustained through continued treatment, a reduced dose of 5mg, or placebo.
In the trial, 441 participants received tirzepatide at the MTD (10mg or 15mg) during a 60-week open-label weight-loss period. At week 60, 378 participants were randomised to continue tirzepatide MTD (N=140), reduce to tirzepatide 5mg (N=144), or switch to placebo (N=94) for a further 52 weeks. Rescue tirzepatide was not permitted between weeks 60 and 84 but was available thereafter. Mean baseline body weight was 113.8 kg, with approximately 55% of participants achieving ≥20% weight loss and 84% reaching a weight plateau by the time of randomisation. Study completion exceeded 90% across all arms.
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Results were presented by Deborah B Horn, DO, MPH, medical director of the UT Physicians Center for Obesity Medicine and Metabolic Performance and clinical assistant professor at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), and Carel W le Roux, MBChB, MSC, FRCP, FRCPath, PhD, director of the Metabolic Medicine Group and Professor of Metabolic Medicine at Ulster University.
Continuation of tirzepatide at either MTD or 5mg was statistically and clinically superior to placebo across primary and key secondary endpoints. At week 112, mean weight change from baseline was −22.4% with MTD (representing 100% maintenance prior to weight reduction), −17.0% with 5mg (~70% maintenance), and −10.1% with placebo. Treatment differences versus placebo were −12.3% for the MTD and −6.9% for 5mg (both p<0.001). The proportion of participants maintaining ≥20% weight loss at Week 112 was 55%, 37%, and 8% in the MTD, 5mg, and placebo arms, respectively.
Cardiometabolic improvements were similarly dose-dependent. Compared with placebo, the MTD arm achieved greater reductions in BMI (−9.0kg/m² versus −4.1kg/m²), waist circumference (−20.1cm versus −8.4cm), systolic blood pressure (−8.7mmHg versus −0.4mmHg), and triglycerides (−27.2% versus −9.6%), with sustained benefits also observed at 5mg. Among participants with pre-diabetes at baseline, normoglycemia was achieved in 92.7% and 84.4% of the MTD and 5mg groups, respectively, versus 51.0% with placebo (p<0.001). Physical functioning also improved significantly with MTD versus placebo. The safety profile was consistent with previous tirzepatide studies, with predominantly mild-to-moderate gastrointestinal adverse events and no new safety signals.
Key opinion leaders interviewed by GlobalData were near-unanimous in recognising tirzepatide as the current best-in-class obesity therapy, citing its superior efficacy over semaglutide, strong tolerability profile, and expanding body of evidence across key comorbidities, including heart failure, sleep apnoea, and cardiovascular outcomes.
Consequently, SURMOUNT-MAINTAIN demonstrated that while MTD allowed for 100% weight loss maintenance, dose reduction to 5mg provided 70% weight loss maintenance, representing a clinically viable and statistically superior alternative to treatment discontinuation; this provides an evidence base for patient-centred dose management, consolidating tirzepatide’s position as a cornerstone of long-term obesity pharmacotherapy. According to GlobalData’s Pharma Intelligence Center, there are currently 48 Phase III, 112 Phase II, and 158 Phase I candidates for overweight and obesity in development globally.
