Tirzepatide reduces weight in women with obesity across reproductive stages

Treatment with tirzepatide, compared with placebo, results in significant reductions in body weight, waist circumference, and waist-to-height ratio (WHtR) among women with obesity or overweight and without type 2 diabetes (T2D), regardless of reproductive stage.

“[T]irzepatide treatment was associated with reduction not just in body weight but in waist circumference and WHtR, which are direct measures of central adiposity that are characteristically exacerbated during the perimenopause stage,” the investigators said.

In this post hoc analysis, female participants from SURMOUNT-1, -3, and -4 who had been randomized to either tirzepatide (15 mg or maximum tolerated dose) or placebo were retrospectively categorized as being in the pre-, peri-, or postmenopause stage.

At the end of study treatment, the investigators assessed the body weight and waist circumference changes, the proportion of participants achieving body weight-reduction thresholds, and WHtR category shift among those with baseline BMI <35 kg/m².

In SURMOUNT-1, tirzepatide treatment was associated with significantly greater body weight reductions from baseline compared with placebo in women in the pre- (26 percent vs 2 percent), peri- (23 percent vs 3 percent), and postmenopause stages (23 percent vs 3 percent; p<0.001). [Obesity 2025;33:851-860]

The tirzepatide arm also demonstrated greater reductions in waist circumference across the subgroups (premenopause: 22 vs 4 cm; perimenopause: 20 vs 5 cm; postmenopause: 20 vs 4 cm; p<0.001).

Across the reproductive stage subgroups, significantly more patients in the tirzepatide arm achieved ≥5-percent body weight reductions than those in the placebo arm (97 percent to 98 percent vs 39 percent to 33 percent). 

In addition, 30 percent to 52 percent of women across the reproductive stage subgroups who had baseline BMI <35 kg/m² achieved WHtR ≤0.49 (low central adiposity) following tirzepatide use.

These findings were also observed in SURMOUNT-3 and -4.

BMI limits

“The decreases in WHtR ... are of clinical relevance due to the measure's association with obesity-related complications and mortality and its superiority to BMI in predicting cardiometabolic risk, particularly with some obesity-related complications in women who are peri- and postmenopausal,” the investigators said. [Korean J Pediatr 2016;59:425-431; Diabetes Metab Syndr Obes 2013;6:403-419]

The American Medical Association has recently issued a statement regarding the limitations of BMI as a standalone clinical metric. [www.ama-assn.org/press-center/press-releases/ama-adopts-new-policy-clarifying-role-bmi-measure-medicine]

“WHtR is an anthropometric measure that is readily applicable to clinical practice due to evidence supporting that the same three categories are appropriate irrespective of sex and race and ethnicity,” the investigators said.  [www.nice.org.uk/guidance/cg189/resources/obesity-identification-assessment-and-management-pdf-35109821097925; Obes Rev 2012;13:275-286;]

Safety

The most common treatment-emergent adverse event (AE) reported was gastrointestinal AEs, such as nausea, diarrhoea, constipation, and vomiting.

These gastrointestinal events were higher among women treated with tirzepatide versus placebo, as usually observed with incretin-based therapies.

"This is consistent with incidences of gastrointestinal-related AEs that have been reported in the primary studies, which were generally transient and mostly mild to moderate in severity and primarily occurred during the dose-escalation period,” the investigators said. [N Engl J Med 2022;387:205-216; Nat Med 2023;29:2909-2918; JAMA 2024;331:38-48]