Body weight reduction in women treated with tirzepatide by reproductive stage: a post hoc analysis from the SURMOUNT program

Abstract

Objective: Increases in adiposity and adverse changes in adipose distribution commonly occur in women during midlife and with the onset of menopause. This post hoc analysis assessed body weight changes with tirzepatide by reproductive stage.

Methods: Women participants from SURMOUNT-1, -3, and -4 randomized to tirzepatide (15 mg or maximum tolerated dose) or placebo were retrospectively categorized as being in the pre-, peri-, or post-menopause stages. Body weight and waist circumference changes, the proportion of participants achieving body weight-reduction thresholds, and waist to height ratio (WHtR) category shift among those with baseline BMI < 35 kg/m² were assessed at end of study treatment.

Results: In SURMOUNT-1, significantly greater body weight reductions from baseline were observed with tirzepatide versus placebo in women in the premenopause (26% vs. 2%), perimenopause (23% vs. 3%), and postmenopause stages (23% vs. 3%; p < 0.001). Greater waist circumference reductions were also observed with tirzepatide across the subgroups (22 vs. 4 cm, 20 vs. 5 cm, and 20 vs. 4 cm, respectively; p < 0.001). Across the reproductive stage subgroups, 97% to 98% of participants achieved body weight reductions that were ≥5% with tirzepatide versus 29% to 33% with placebo. Furthermore, 30% to 52% of women among the reproductive stage subgroups who had baseline BMI < 35 kg/m² reached WHtR ≤ 0.49 (low central adiposity) with tirzepatide. Similar results were observed in SURMOUNT-3 and -4.

Conclusions: In this post hoc analysis, tirzepatide treatment was associated with significant body weight, waist circumference, and WHtR reductions versus placebo in women living with obesity or overweight and without type 2 diabetes, irrespective of reproductive stage.

FIGURE 1

Change in percent body weight and waist circumference by reproductive stage subgroup in SURMOUNT‐1. Data are proportion of participants who met weight‐reduction threshold at the primary endpoint. Logistic regression with missing value imputed by mixed model for repeated meaures (MMRM) at the primary endpoint was used to assess proportion of participants who met weight‐reduction thresholds. Data from the tirzepatide 15‐mg arm from SURMOUNT‐1 are shown vs. placebo. The denominator used to calculate proportion of participants achieving weight‐loss goals was the number of participants in imputed data. *p < 0.05 and **p < 0.001 vs. baseline and ^## p < 0.001 vs. placebo.

FIGURE 2

Percent body weight change over time by reproductive stage subgroup in SURMOUNT‐1. Data are least squares mean (SE) percent change from baseline in body weight over time in participants treated with tirzepatide 15 mg.

FIGURE 3

Categorical weight‐loss outcomes by reproductive stage subgroup in SURMOUNT‐1. Data are proportion of participants who met weight‐reduction threshold at the primary endpoint. Logistic regression with missing value imputed by mixed model for repeated measures (MMRM) at the primary endpoint was used to assess proportion of participants who met weight‐reduction thresholds. Data from the tirzepatide 15‐mg arm from SURMOUNT‐1 are shown vs. placebo. The denominator used to calculate proportion of participants achieving weight‐loss goals was the number of participants in imputed data. ^# p < 0.05 and ^## p < 0.001 vs. placebo.

FIGURE 4

WHtR by reproductive stage subgroup among participants with baseline BMI < 35 kg/m² in SURMOUNT‐1. Data show shift in WHtR from baseline to the primary endpoint of 72 weeks. Postbaseline values are the last nonmissing value. Grand total was used as the denominator to calculate percentages in each treatment. WHtR, waist to height ratio.