People living with obesity who continued tirzepatide after achieving initial weight loss maintained substantially greater long-term bodyweight reduction than those who discontinued treatment, according to findings from the SURMOUNT MAINTAIN trial presented at the European Congress on Obesity 2026 and simultaneously published in The Lancet. The authors stated that “as happens in other chronic diseases,” obesity relapsed in most cases if treatment was stopped.
The phase 3b, placebo-controlled study evaluated whether continuing tirzepatide at the maximum tolerated dose (10 mg or 15 mg) or reducing therapy to 5 mg could preserve weight reduction achieved during an initial 60-week lead-in period. The 112-week trial enrolled 441 adults with obesity or overweight and at least one weight-related complication across 20 US centers. Baseline mean bodyweight was 113.8 kg, mean body mass index (BMI) was 40.1 kg/m², and mean glycated hemoglobin (HbA1c) was 5.64%.
Participants who achieved at least 5% bodyweight reduction during the lead-in phase and tolerated tirzepatide 10 mg or 15 mg entered the randomized maintenance phase. A total of 378 participants were assigned to continue the tirzepatide maximum tolerated dose, reduce therapy to tirzepatide 5 mg, or switch to placebo for an additional 52 weeks. Overall, study completion during the maintenance phase reached 91.3%.
At week 112, the estimated mean bodyweight change from baseline was −21.9% among participants continuing tirzepatide at the maximum tolerated dose, compared with −16.6% with tirzepatide 5 mg and −9.9% with placebo. Participants continuing maximum tolerated dose therapy maintained nearly all prior weight reduction, with minimal weight regain after randomization, whereas mean regain reached 6 kg with tirzepatide 5 mg and 13 kg after placebo switch.
Among participants who reached a bodyweight plateau before randomization, continued tirzepatide maximum tolerated dose maintained 96.5% of bodyweight reduction achieved during the weight-loss period, while tirzepatide 5 mg maintained 67.9% compared with 42.8% for placebo. In addition, at least 80% of prior bodyweight reduction was maintained in 77.5% of participants continuing tirzepatide maximum tolerated dose versus 42.4% receiving tirzepatide 5 mg and 10.4% switched to placebo. The authors noted that the odds of maintaining at least 80% of lost bodyweight were approximately seven times higher with continued maximum tolerated dose therapy and four times higher with tirzepatide 5 mg compared with placebo.
Rescue tirzepatide could be introduced after week 84 if participants regained more than 50% of their prior weight loss. Rescue therapy was required in 67% of participants switched to placebo, compared with 25% receiving tirzepatide 5 mg and 8% continuing maximum tolerated dose treatment. Improvements across prespecified cardiometabolic measures were maintained with continued tirzepatide therapy but showed greater reversal after placebo discontinuation.
The most commonly reported adverse events were gastrointestinal events, which were mostly mild-to-moderate in severity and occurred primarily during dose escalation. The authors stated that discontinuation of effective obesity treatment “resulted in reversal of therapeutic benefit and caused significant weight regain, often back towards the pretreatment bodyweight over time.” They added that continued tirzepatide maximum tolerated dose preserved improvements in waist circumference, blood pressure, lipids, and quality of life to a greater extent than dose reduction or treatment discontinuation.
The authors concluded that “long-term therapy is important for maintaining bodyweight reductions and cardiometabolic benefits in adults with obesity” and stated that the findings “underscore the importance of continued therapy for long-term obesity management and provide evidence for what to expect when reducing the dosage of obesity treatment.”
