Tirzepatide Maintained Weight Loss In SURMOUNT-MAINTAIN

Key Takeaways

• Continued tirzepatide at the maximum tolerated dose was associated with greater maintenance of bodyweight reduction than switching to placebo at week 112.
• The 5 mg group showed an intermediate result, and rescue therapy after substantial regain was more common with placebo.
• Gastrointestinal events were the main adverse events, were mostly mild to moderate, and were concentrated during dose escalation; the authors concluded that long-term treatment was often needed to maintain bodyweight reduction.

After an initial weight-loss phase, continued tirzepatide at the maximum tolerated dose preserved more bodyweight reduction through week 112 than switching to placebo in SURMOUNT-MAINTAIN. Modeled bodyweight change from baseline at week 112 was -21.9% with continued maximum tolerated dosing and -9.9% after switching to placebo, with the 5 mg group falling between those results. In this phase 3b, placebo-controlled, 112-week trial in adults with obesity, the maintenance phase tested whether weight-loss reduction was sustained when therapy continued, was reduced, or was withdrawn.

The study ran across 20 US sites, with a 60-week open-label tirzepatide weight-loss period followed by a 52-week double-blind maintenance phase. Adults who completed the initial treatment period were randomized in a 3:3:2 ratio to continue maximum tolerated dose tirzepatide, reduce to 5 mg, or switch to placebo. At week 60, 378 participants were randomized, 372 received at least one maintenance dose, and 345 of 378 completed the study. Participants were 65% female, had a mean age of 46.6 years, and entered the trial with mean bodyweight 113.8 kg and BMI 40.1 kg/m2. Percentage change in bodyweight from baseline to week 112 was the primary endpoint for the maintenance comparison.

Model-based bodyweight change at week 112 was -21.9% with maximum tolerated dose tirzepatide, -16.6% with 5 mg, and -9.9% with placebo. The corresponding 95% confidence intervals were -23.5 to -20.3, -18.0 to -15.1, and -11.1 to -8.8, respectively. Estimated treatment differences versus placebo were -12.0% for continued maximum tolerated dosing and -6.6% for 5 mg, with p<0.0001 for all comparisons. The 95% confidence intervals for those differences were -13.8 to -10.1 and -8.3 to -5.0, leaving the 5 mg group between continued treatment and withdrawal.

Rescue tirzepatide could start at week 84, 24 weeks after random allocation, for participants whose weight regain exceeded 50% of lost bodyweight. Rescue use occurred in 11 of 138 participants in the maximum tolerated dose group, 35 of 142 in the 5 mg group, and 60 of 90 with placebo. The most common adverse events with tirzepatide were gastrointestinal events; these were mostly mild to moderate and occurred mainly during dose escalation.

The authors concluded that long-term treatment was often necessary to maintain bodyweight reduction, and that 5 mg might offer an alternative to discontinuation. Rescue use and weight change followed the same stepped pattern across the three groups.