Combined Menopausal Hormone Therapy and Semaglutide May Improve Glucose Homeostasis in Postmenopausal Women with Diabetes

Postmenopausal women often experience significant metabolic shifts, including decreased insulin sensitivity, increased visceral adiposity, and elevated risk for type 2 diabetes and cardiovascular disease, largely due to declining estrogen levels. While GLP-1 receptor agonists (GLP-1RAs) like semaglutide are highly effective for managing diabetes and obesity, their full potential in this specific population, particularly when combined with Menopausal Hormone Therapy (MHT), remains underexplored. This trial aims to address whether restoring estradiol (E2) levels via MHT can synergistically enhance the beneficial metabolic effects of GLP-1RAs, offering a more comprehensive approach to glucose and energy homeostasis in this vulnerable group.

This randomized clinical trial, currently recruiting, will enroll 96 early postmenopausal women with pre- or existing type 2 diabetes. Participants will be assigned to one of three arms: Menopausal Hormone Therapy alone (Estradot® 50 micrograms/24h transdermal E2, plus Utrogestan® 200mg daily micronized progesterone for those with intact uterus); GLP-1 Receptor Agonist alone (Wegovy® semaglutide, injected once weekly starting at 0.25mg and escalating to 1mg over eight weeks); or a Combined therapy arm receiving both MHT and GLP-1RA. The primary objective is to assess the efficacy of combined therapy in improving glucose control compared to GLP-1RA alone, with secondary endpoints including changes in body weight, other cardiometabolic health markers, and menopausal symptoms.