Menopausal Hormone Therapy, GLP-1 Agonists, and Glucose and Energy Homeostasis in Postmenopausal Women With Diabetes

NCT ID: NCT06715514

Last Updated: 2025-03-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-18
• Study Completion Date: 2026-08-31

Brief Summary

The overall aim is to investigate the hypothesis that restoring E2 levels through MHT improves glucose and energy homeostasis and potentiates the beneficial effects of GLP-1RA in early postmenopausal women with pre- or existing type 2 diabetes.

The primary objective is to assess the efficacy of combined MHT and GLP-1RA in improving glucose control in early postmenopausal women with pre- or existing type 2 diabetes, compared to GLP-1RA alone. Secondary objectives include efficacy analyses on body weight, other measures of cardiometabolic health, lifestyle behaviour, menopausal symptoms, and the exploration of mechanisms underpinning potential glycaemic and weight control benefits, and biomarkers of haemostasis.

Detailed Description

The menopausal-related decline in estradiol (E2) levels challenges glucose and energy homeostasis, exemplified by an increased risk of diabetes development or worsening of glucose in pre-existing diabetes. Conversely, restoration of E2 exposure using menopausal hormonal therapy (MHT) benefits body weight and glucose control. However, underlying mechanisms remain incompletely understood. In this context, we hypothesize an involvement of the GLP-1 gut-pancreas/brain axis, but supporting clinical evidence is currently lacking.

The overall aim is to investigate the hypothesis that restoring E2 levels through MHT improves glucose and energy homeostasis and potentiates the beneficial effects of GLP-1RA in early postmenopausal women with pre- or existing type 2 diabetes.

The primary objective is to assess the efficacy of combined MHT and GLP-1RA in improving glucose control in early postmenopausal women with pre- or existing type 2 diabetes, compared to GLP-1RA alone. Secondary objectives include efficacy analyses on body weight, other measures of cardiometabolic health, lifestyle behaviour, menopausal symptoms, and the exploration of mechanisms underpinning potential glycaemic and weight control benefits, and biomarkers of haemostasis.

Conditions

Menopause; Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Menopausal Hormone Therapy

Estradot®: 50 micrograms/24h, transdermal patch E2;

Utrogestan®*: once daily 200mg of micronized progesterone (in women with intact uterus*)

Group Type: OTHER

Menopausal Hormone Therapy

Intervention Type: DRUG

Estradot® and Utrogestan®\* (in women with intact uterus\*)

GLP-1 Receptor Agonist

Wegovy®: Semaglutide injected once weekly, starting dose 0.25mg, with dose increments every four weeks reaching the maintenance dose of 1mg after eight weeks

Group Type: ACTIVE_COMPARATOR

GLP-1 Receptor Agonist

Intervention Type: DRUG

Wegovy®

Combined Menopausal Hornome Therapy and GLP-1 Receptor Agonist

Wegovy®: Semaglutide injected once weekly, starting dose 0.25mg, with dose increments every four weeks reaching the maintenance dose of 1mg after eight weeks; Estradot®: 50 micrograms/24h, transdermal patch E2; Utrogestan®\*: once daily 200mg of micronized progesterone (in women with intact uterus)

Group Type: EXPERIMENTAL

GLP-1 Receptor Agonist

Intervention Type: DRUG

Wegovy®

Menopausal Hormone Therapy

Intervention Type: DRUG

Estradot® and Utrogestan®\* (in women with intact uterus\*)

Interventions

GLP-1 Receptor Agonist

Wegovy®

Intervention Type: DRUG

Menopausal Hormone Therapy

Estradot® and Utrogestan®\* (in women with intact uterus\*)

Intervention Type: DRUG

Other Intervention Names

Semaglutide; Estradiol; Micronized Progesterone

Eligibility Criteria

Inclusion Criteria

• Early postmenopausal status (STRAW+10 stage +1b or +1c and FSH>25.0mU/L)
• Presence of menopausal symptoms (total MRS-II score ≥1)
• BMI ≥ 27.0kg/m2
• Pre- or existing type 2 diabetes (HbA1c 5.7%-8.5%)
• No prior or current use of MHT

Exclusion Criteria

• DPP4-inhibitor, SLGT2-inhibitor or sulfonylurea use within 8 weeks prior to study enrolment
• GLP-1RA use within 6 months prior to study enrolment
• Insulin therapy within 8 weeks prior to study enrolment
• History of bariatric surgery
• More than 2% change in body weight within three months prior to study enrolment (based on documented or reported weights)
• Contraindications for the use of the study medication as per prescription labelling: Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
• Known or suspected cancer of breast or other sexual organ, abnormal genital bleeding of unknown cause, hepatic neoplasia
• Arterial or venous thromboembolic events, porphyria
• Known allergy or hypersensitivity to Wegovy®, Estradot® or Utrogestan® (pharmaceutical agents or any of the excipients)
• Systemic hormone therapy or hormonal contraceptives (e.g. estrogens, progestogens, androgens) during the study and within 12 months prior to participation
• Herbal remedies and complimentary medicines for menopausal symptoms during the study
• Physical or psychological condition or any medical intervention (including medication not specified above) likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
• Participation in another clinical trial that interferes with the interpretation of the study results
• Inability to read German
• Unwillingness to follow the study procedures

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Lia Bally

OTHER

Sponsor Role: lead

Responsible Party

Lia Bally

Prof. Dr. med. et phil.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Prof. Dr. med. et Dr. phil.Lia Bally

Role: PRINCIPAL_INVESTIGATOR

Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital

Locations

University Hospital Bern

Bern, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Prof. Dr. med. et Dr. phil.Lia Bally

Role: CONTACT

lia.bally@insel.ch

+41 31 632 36 77

Facility Contacts

Prof. Dr. med. Dr. phil. Lia Bally

Role: primary

lia.bally@insel.ch

0041 31 63 2 36 77

Other Identifiers

10000574

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2024-01882

Identifier Type: REGISTRY

Identifier Source: secondary_id

DECLARED-CT

Identifier Type: -

Identifier Source: org_study_id