Achieving Waist Circumference Targets with Once Weekly Tirzepatide for the Treatment of Obesity

Objective:
Waist circumference has emerged as a strong marker for predicting morbidity and mortality independent of body mass index (BMI), and an important clinical parameter to assess cardiometabolic risk associated with excess adiposity in obesity. In SURMOUNT-1, waist circumference was significantly reduced in participants treated with once-weekly tirzepatide compared with placebo. We report here the efficacy of tirzepatide compared with placebo regarding the proportion of participants achieving waist circumference targets in SURMOUNT-1.

Methods:
Waist circumference was measured during scheduled visits in the SURMOUNT-1 trial using a non-stretchable measuring tape, per protocol. Waist circumference targets by sex and baseline BMI category were based on recommendations for white individuals by the National Institutes of Health and the International Atherosclerosis Society and International Chair on Cardiometabolic Risk Working Group on Visceral Obesity. Participants with a valid baseline waist circumference value and ≥1 post-baseline value were included in the analysis. Treatment comparisons were performed via a logistic regression model. Missing values at week 72 were imputed by the predicted value from a mixed model for repeated measures using the efficacy analysis set.

Results:
At week 72, the proportion of female participants achieving waist circumference ≤88 cm with tirzepatide 5, 10, 15 mg, and placebo was 32.3% (odds ratio versus placebo [OR] 18.4 [95% confidence interval 10.5, 32.3]), 47.4% (OR 52.8 [29.6, 94.0]), 46.7% (OR 47.2 [26.6, 83.8]), and 4.3%, respectively (p < 0.001 for all odds). Proportions of male participants achieving waist circumference ≤102 cm were 39.6% (OR 10.2 [5.2, 20.1]), 45.0% (OR 24.9 [12.1, 51.3]), 47.8% (OR 30.9 [14.9, 64.1]), and 9.1%, respectively (p < 0.001 for all odds).

Adjusting for gender and BMI categories, overall, the odds of achieving waist circumference goals were significantly greater with all doses of tirzepatide: ORs versus placebo were 6.1 (95% CI 4.1, 9.1), 15.5 (9.9, 24.3), and 18.5 (11.6, 29.5) with tirzepatide 5, 10, and 15 mg, respectively (all p<0.001). Among participants with overweight, 84% (p < 0.05), 76% (p>0.05), and 88% (p < 0.05) achieved waist circumference targets with tirzepatide 5, 10, and 15 mg, respectively, versus 36% with placebo. For class I obesity, the proportions were 84%, 98%, and 88% versus 53%, respectively, and for class II and III obesity, 66%, 77%, and 83% versus 30%, respectively (p < 0.001 for all odds).

Discussion/Conclusion:
In SURMOUNT-1, tirzepatide once weekly resulted in significantly greater proportions of participants achieving waist circumference targets overall and by sex and BMI category than placebo.