Tirzepatide improves waist-to-height ratio in adults with obesity or overweight

This post-hoc analysis of a Phase 3 randomized controlled trial evaluated the effect of tirzepatide on waist-to-height ratio (WHtR) in adults with obesity or overweight. The study included 2538 adults with a BMI of 30 kg/m² or greater, or 27 kg/m² or greater with at least one obesity-related complication, excluding diabetes. The intervention was once-weekly tirzepatide at doses of 5, 10, or 15 mg, combined with a reduced-calorie diet and increased physical activity. The comparator was placebo with the same lifestyle intervention. The follow-up period was 16.6 months (72 weeks), with additional follow-up to 176 weeks for participants with prediabetes.

The primary outcome of the original trial was not reported; this analysis focused on shifts in WHtR categories. At 72 weeks, 16.7% of participants receiving tirzepatide (10/15 mg) achieved a WHtR of 0.49 or less, compared to a rate not reported for placebo. Additionally, 54.7% of participants in the tirzepatide group improved their WHtR category, versus 9.6% in the placebo group. Among participants with prediabetes, at 176 weeks, 12.2% on tirzepatide achieved WHtR 0.49 or less, compared to 9.3% on placebo, and 46.4% improved their WHtR category versus 9.3% on placebo. Effect sizes, confidence intervals, and p-values were not reported.

Safety and tolerability data were not reported in this post-hoc analysis. The study did not provide details on adverse events, serious adverse events, or discontinuations.

Compared to prior landmark studies, tirzepatide has been shown to reduce body weight and improve glycemic control in obesity and type 2 diabetes. This analysis extends those findings by examining WHtR, a measure of central adiposity and cardiometabolic risk. However, the post-hoc nature and lack of a primary outcome limit the strength of these conclusions.

Key methodological limitations include the post-hoc design, which increases the risk of bias and false-positive findings. Not all participants had prediabetes at baseline, so long-term data are limited to those with prediabetes. The absence of p-values and confidence intervals prevents assessment of statistical precision.

Clinically, these results suggest that tirzepatide may improve central adiposity as measured by WHtR, but the evidence is low certainty. Clinicians should consider these findings as supportive but not definitive. The WHtR is a surrogate outcome, and its direct clinical benefit remains unproven.

Unanswered questions include whether WHtR improvements translate to reduced cardiovascular events, the durability of effect beyond 176 weeks, and the comparative effectiveness of different tirzepatide doses. Further prospective trials with WHtR as a primary endpoint are needed.