(3.05) Waist-to-height ratio shifts over time in tirzepatide-treated participants – post hoc analysis in SURMOUNT-1 and SURMOUNT-2

Thursday, May 9, 2024

11:05 AM – 11:20 AM CDT

Location: ePoster Showcase, Empire Ballroom Foyer, Level 2

Submitter(s)

Beverly Tchang, MD

Assistant Professor of Clinical Medicine
Weill Cornell Medicine
New York, New York, United States

Objective : Waist-to-height ratio (WHtR) is a practical estimate of central adiposity and can be a better predictor of cardiometabolic disease than body mass index (BMI). Tirzepatide (TZP) is a once weekly GIP/GLP-1 receptor agonist approved in the US for treatment of type 2 diabetes and obesity. The objectives of this post hoc analyses of SURMOUNT-1 (SM-1) and SURMOUNT-2 (SM-2) were to assess change from baseline (BL) to Week 72 in WHtR and to assess shift from BL to Week 72 in WHtR risk categories as defined by recent NICE guidelines for individuals with BMI < 35 kg/m²: “healthy” (WHtR ≤0.49), “increased” (WHtR >0.49 to ≤0.59), and “high” (WHtR >0.59).

Methods:

Post hoc analyses included 737 participants with obesity or overweight with a weight related complication in SM-1 and 474 participants with obesity or overweight and type 2 diabetes in SM-2 who had BL BMI < 35 kg/m². Analyses used efficacy analysis sets (on-treatment data in participants with ≥ 1 dose of study drug) and the last non-missing value for WHtR. Changes from BL to Week 72 in WHtR were compared between pooled TZP 10/15 mg and placebo (PBO) using mixed model for repeated measures. The proportion of participants reaching WHtR category thresholds were also evaluated.

Results:

In SM-1, TZP treated participants achieved a significantly greater WHtR reduction compared to PBO at Week 72 (-0.11 vs. -0.02, p< 0.001). Furthermore, TZP participants (n=486) had substantial shifts in WHtR risk categories from BL to Week 72: “healthy” 0% to 30.9%, “increased” 25.5% to 54.7%, and “high” 74.5% to 13.0%. The PBO participants (n=251) had limited shifts in WHtR risk categories from BL to Week 72: “healthy” 0.4% to 2.0%, “increased” 22.3% to 35.5%, and “high” 77.3% to 61.0%.
In SM-2, TZP treated participants achieved a significantly greater WHtR reduction compared to PBO at Week 72 (-0.07 vs -0.02, p< 0.001). Furthermore, TZP participants (n=317) had substantial shifts in WHtR risk categories from BL to Week 72: “healthy” 0% to 9.5%, “increased” 20.2% to 52.7%, and “high” 79.8% to 36.9%. The PBO participants (n=157) had limited shifts in WHtR risk categories from BL to Week 72: “healthy” 0% to 1.3%, “increased” 23.6% to 33.8%, and “high” 76.4% to 63.1%.

Discussion/Conclusion:

Treatment with TZP resulted in a significant reduction of WHtR and a shift to lower WHtR risk categories, with more individuals in “healthy,” fewer in “high,” and more moving from “high” to “increased” categories. Future studies could further elucidate the effect of TZP on other cardiometabolic parameters and outcomes and how changes in WHtR may explain any such benefits.