Drug Combination May Boost Weight Loss in Older Women, Study Finds

A new study suggests that combining a popular weight-loss drug with menopausal hormone therapy could significantly improve outcomes for older women struggling with weight gain during midlife.

Researchers at the Mayo Clinic and Wayne State University analyzed health data from 120 women, mostly White and in their 50s, who were using tirzepatide, a GLP-1 based medication sold under the brand names Zepbound or Mounjaro. Of those, 40 were also taking menopausal hormone therapy alongside the drug, while 80 used tirzepatide alone. Their health was tracked for an average of 18 months.

The results showed a notable difference between the two groups. Women using both tirzepatide and hormone therapy lost an average of 19.2 percent of their starting body weight, compared to 14 percent among those on tirzepatide alone. That 5.2 percentage point gap is statistically significant, and a higher share of the combination group achieved 30 percent or more total body weight loss over 15 months.

These findings build on a 2024 study by some of the same researchers, which found similar advantages when menopausal hormone therapy was combined with semaglutide, another GLP-1 drug.

Lead researcher Regina Castaneda of the Mayo Clinic Center noted that the scale of the difference justifies further investigation into how the two treatments may interact. However, the exact reason behind the improved results remains unclear. Senior author and endocrinologist Maria Daniela Hurtado Andrade noted that women on hormone therapy may have already practiced healthier habits, or that relief from menopause symptoms such as poor sleep may have made it easier to stick to lifestyle changes.

The study did not distinguish between different types or doses of hormone therapy, which is a recognised limitation. Researchers are now planning a randomised controlled trial to confirm the findings and explore whether the combination also improves broader heart and metabolic health.

The research was published in The Lancet Obstetrics, Gynaecology, and Women's Health.