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Tirzepatide plus hormone therapy increases weight loss

Written by | 13 Jul 2025 | Medicines and Therapeutics

Simultaneous treatment with tirzepatide and menopause hormone therapy results in greater weight loss in postmenopausal women who are overweight or obese than tirzepatide monotherapy, researchers reported on July 12, 2025 at ENDO 2025, the Endocrine Society’s annual meeting.

“These data are the first to show the combined use of tirzepatide and menopause hormone therapy significantly increases treatment effectiveness in postmenopausal women,” said Regina Castaneda, M.D., research fellow for the Division of Endocrinology at the Mayo Clinic in Jacksonville, Fla. “Previous studies of the medication semaglutide found similar results. Achieving these outcomes with a second obesity medication may indicate a broader efficacy trend for pairing these two classes of medications.”

For this retrospective study the investigators enrolled postmenopausal women who had been prescribed tirzepatide for treatment of being overweight or obese, with or without menopause hormone therapy.

Exclusion criteria were treatment for less than 12 months with tirzepatide, prior bariatric surgery, active malignancy and concomitant anti-obesity medication use.

Menopause hormone therapy consisted of transdermal or oral estrogen, with or without progesterone.

The primary endpoints of the study were total body weight loss percentage at 3, 6, 9, 12, and 15 months, and at last follow-up.

The researchers included 120 subjects in this analysis, 40  in the menopause hormone therapy + tirzepatide group (mean age 56 years, mean BMI 34  kg/m2) and 80 in the tirzepatide-only group (mean age 57 years, mean BMI 33 kg/m2).

The median follow-up duration was 18 months for the menopause hormone therapy + tirzepatide group and 18 months for the tirzepatide-only group.

At the last follow-up, the subjects using menopause hormone therapy + tirzepatide group achieved significantly greater total body weight loss (17% vs 14%,   p=0.01) compared to the tirzepatide monotherapy group.

And by the last follow-up, a higher proportion of women in the menopause hormone therapy + tirzepatide group achieved ≥20% total body weight loss compared to the tirzepatide monotherapy group (45% vs. 18%, p=0.001).

The researchers concluded, “In postmenopausal women with overweight or obesity treated with TZP [tirzepatide], the use of MHT [menopause hormone therapy] is associated with superior weight loss outcomes.

“The information garnered through this new study provides important insights to develop more effective and personalized weight management interventions to reduce a postmenopausal woman’s risk of overweight and obesity-related health complications,” added Maria Daniela Hurtado Andrade, M.D., Ph.D., assistant professor of medicine and consultant for the Division of Endocrinology at the Mayo Clinic.

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