SURMOUNT-MAINTAIN trial

The SURMOUNT-MAINTAIN trial evaluated the efficacy and safety of continuing tirzepatide at the maximum tolerated dose (MTD) or lowering the dose to 5 mg compared with switching to placebo on the maintenance of bodyweight reduction obtained with tirzepatide MTD in adults with obesity (1):

• phase 3b, placebo-controlled, 112-week trial, including a 60-week open-label weight-loss period and a 52-week, double-blind weight maintenance period, was conducted across 20 sites in the USA
• after completing the initial weight-loss period with once weekly subcutaneous tirzepatide at the MTD (10 mg or 15 mg), adults (aged ≥18 years) with a BMI of 30 kg/m² and above or 27 kg/m² and above with one or more weight-related comorbidity, and a history of at least one self-reported unsuccessful dietary effort to lose bodyweight were randomly assigned in a 3:3:2 ratio to continue tirzepatide MTD, reduce to tirzepatide 5 mg, or switch to placebo for an additional 52 weeks
• starting at week 84 (24 weeks after random allocation), participants could receive rescue tirzepatide if their weight regain exceeded 50%
• primary endpoint was the percentage change in bodyweight from baseline to week 112

Study results:

• from Sept 20, 2023, to Jan 20, 2026, 441 patients were enrolled in and took at least one dose of study treatment during the weight-loss period, with 378 participants randomly allocated at week 60 (140 to tirzepatide MTD; 144 to dose-reduction to 5 mg tirzepatide; and 94 to placebo)
  • at baseline, participants had a mean bodyweight of 113·8 kg (SD 27·0), a BMI of 40·1 kg/m² (SD 8·1), and HbA_1c 5·64% (SD 0·4; 38·2 mmol/mol [SD 4·0]).
  • 372 received at least one dose of study drug during the weight maintenance period (139 for tirzepatide MTD; 142 for 5 mg tirzepatide; and 91 for placebo)
  • 345 (91%) of 378 participants completed the study
  • majority of participants were White (67%); 288 (65%) participants were female and 153 (35%) were male; and the mean age was 46·6 years (SD 13·0)
  • model-based estimate per cent change in bodyweight from baseline to week 112 was
    • –21·9% (95% CI –23·5 to –20·3) with MTD (estimated treatment difference [ETD] –12·0% [95% CI –13·8 to –10·1]),
    • –16·6% (95% CI –18·0 to –15·1) with 5 mg tirzepatide (ETD –6·6 [95% CI –8·3 to –5·0]),
    • –9·9% (95% CI –11·1 to –8·8) with placebo (p<0·0001 for all comparisons)
  • among participants who regained at least 50% of lost bodyweight, observed means were 11 (8%) of 138, 35 (25%) of 142, and 60 (67%) of 90 participants received rescue therapy in the tirzepatide MTD, 5 mg tirzepatide, and placebo, respectively
  • most common adverse events with tirzepatide were gastrointestinal events, which were mostly mild to moderate in severity and mostly occurred during dose escalation

The study authors noted: “In the SURMOUNT-MAINTAIN trial, continuing tirzepatide at MTD maintained bodyweight reduction and health-related benefits. Reducing to 5 mg tirzepatide might provide a valuable alternative to discontinuation, although individuals’ treatment response might vary. Together, these findings support the importance of ongoing therapy for long-term obesity management and provide evidence to inform individualised, patient-centred obesity care.”

Reference:

1. Horn D, Aronne L, Wharton S et al.Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial. The Lancet, 2026.