In patients with obesity, continuing tirzepatide at either the maximum tolerated dose (MTD) of 10 or 15 mg or a reduced dose of 5 mg was safe and effectively maintained weight loss along with its associated health benefits, compared to switching to placebo, according to results from the SURMOUNT-MAINTAIN trial published May 12 in The Lancet.

Investigators enrolled 441 adult patients in the U.S. into a 60-week open-label weight loss period with once-weekly subcutaneous tirzepatide, followed by a 52-week, double-blind weight maintenance period. Participants had a BMI ≥30 kg/m² or BMI ≥27 kg/m² plus one or more weight-related comorbidities and prior unsuccessful weight loss efforts. Baseline mean body weight was 113.8 kg, mean BMI was 40.1 kg/m² and median duration of obesity was 13 years. Their mean age was 47 years, 65% were women and most (67%) were White.

For the weight maintenance period, 378 participants who had lost ≥5% of their body weight and could tolerate at least 10 mg tirzepatide were randomized 3:3:2 to once-weekly tirzepatide MTD (n=140), tirzepatide 5 mg (n=144) or placebo (n=94). All participants received lifestyle interventions throughout the trial, including dietary and physical activity counseling.

Notably, rescue tirzepatide was allowed for participants who regained >50% of their weight loss, starting at 24 weeks post randomization.

At the end of the 112-week trial, the primary endpoint of percent change in weight from baseline was –21.9% with tirzepatide MTD, –16.6% with tirzepatide 5 mg and –9.9% with placebo. The estimated treatment differences were –12.0% with tirzepatide MTD and –6.6% with 5 mg compared with placebo (p<0.0001).

Only 8% of patients in the tirzepatide MTD and 25% in the tirzepatide 5 mg groups regained at least 50% of what they had lost, compared with 67% of the placebo group; they were treated with rescue tirzepatide.

Also observed were improvements in BMI, waist circumference, glycemia, blood pressure and lipid profile with both doses of tirzepatide vs. placebo.

During the weight loss period, 20 participants reported serious adverse events, while during the weight maintenance period, two patients in the 5 mg group and one in the placebo group experienced a serious adverse event. In the weight maintenance period, the incidence of all adverse events was higher with tirzepatide than placebo. Mild-to-moderate gastrointestinal issues were most common.

"Combined, these findings underscore the importance of continued therapy for long-term obesity management and provide evidence for what to expect when reducing the intensity of obesity treatment," write Deborah B. Horn, DO, et al.

"The clinical rationale for continuing pharmacotherapy at the lowest effective dose for weight maintenance has been acknowledged, but without specific evidence for low-dose regimens individualized approaches and further research have been called for," writes André J. Scheen, MD, in an accompanying editorial comment. "In this complex topic of major clinical interest, SURMOUNT-MAINTAIN now provides information on the effect of dose reduction on the maintenance of bodyweight reduction for the first time in a dedicated RCT."