(3.04) Evaluating the Association Between Early Body Weight Changes with Tirzepatide and Categorical Weight Reduction in People with Obesity or Overweight: a Post-Hoc Analysis

Tirzepatide, a once weekly GIP/GLP-1 receptor agonist, demonstrated robust weight reduction efficacy, with body weight reductions of 13-23% in people with obesity or overweight in the SURMOUNT-1 (SM-1; participants without type 2 diabetes [T2D]) and SURMOUNT-2 (SM-2; participants with T2D) trials. In this post-hoc analysis, we aimed to describe week 24 weight loss by categorical weight reduction at the end of study (week 72), to provide insights to weight loss trajectories when considering individualized weight reduction targets.

Methods:

Data from tirzepatide-treated participants who received ≥75% doses in SM-1 (N=1596) and SM-2 (N=532) were included in the analysis. Data were pooled for all doses in each study and summarized descriptively for week 72 categorical weight reductions of ≥5% to < 10%, ≥10% to < 15%, ≥15% to < 20%, ≥20% to < 25%, or ≥25%.

Results:

At baseline, mean age was 45 years, weight 104.8 kg, and BMI 38.0 kg/m² in SM-1, and 54 years, 101.1 kg, and 36.1 kg/m² in SM-2. 68% and 50% of participants were female in SM-1 and -2, respectively.

SM-1 participants with weight reduction of ≥5% to < 10%, ≥10% to < 15%, ≥15% to < 20%, ≥20% to < 25%, or ≥25% at week 72 had mean weight change at week 24 (95% confidence interval [CI]) of -7.8% ( -8.3, -7.2), -10.1% (-10.6, -9.6), -12.7% (-13.1, -12.2), -14.8% (-15.3, -14.4), and -18.9% (-19.3, -18.4), respectively. The corresponding weight change for SM-2 participants was -7.5% (-8.2, -6.7), -9.8% (-10.5, -9.1), -12.2% (-12.9, -11.5), -14.5% (-15.4, -13.7), and -18.6% (-19.7, -17.4) at week 24, respectively.

When assessing body weight change in females and males, in SM-1, mean weight change at week 24 was -7.6% (95% CI -8.5, -6.8), -9.9% (-10.6, -9.3), -12.6% (-13.2, -12.0), -14.5% (-15.0, -14.0), and -19.0% (-19.5, -18.5) in females, and -7.9% (-8.7, -7.1), -10.3% (-11.1, -9.5), -12.8% (-13.6, -12.0), -15.7% (-16.6, -14.8), and -18.4% (-19.4, -17.4) in males, for each of the week 72 weight reduction categories, respectively. In SM-2, mean weight change at week 24 was -7.2% (95% CI -8.5, -5.9), -10.3% (-11.5, -9.1), -12.1% (-13.0, -11.2), -14.3% (-15.3, -13.3), and -17.9% (-19.1, -16.8) in females, and -7.7% (-8.6, -6.7), -9.4% (-10.2, -8.6), -12.2% (-13.2, -11.2), -15.0% (-16.9, -13.1), and -19.9% (-22.5, -17.2) in males, respectively.

Discussion/Conclusion:

In SM-1 and -2, participants reached at least 70% of their week 72 weight reduction by week 24. Within week 72 weight reduction categories, males tended to have more weight reduction by week 24 than females, suggesting sex-specific trajectories. These data may be useful in clinical decision making when considering dose adjustments to achieve individualized weight reduction targets.