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

NCT06715514 | Recruiting

• 3 other identifiers: DECLARED-CT100005742024-01882
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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.

Conditions

Menopause; Type 2 Diabetes

Keywords

Diabetes; Menopause; Menopausal Hormone Therapy; Womens Health; Randomized Controlled Trial; GLP-1 receptor agonist

Outcome Measures

Primary Outcomes (1)

• Change in HbA1C

  Change in HbA1C from Baseline (Visit 1a) to Visit 2a (units: percentage points). The primary outcome will be compared between the combined MHT+GLP-1RA arm and the GLP-1RA only arm.

  12 Weeks

Secondary Outcomes (14)

• Change in postprandial plasma glucose exposure during the OGTT (AUC plasma glucose concentration)

  12 Weeks

• Change in average sensor glucose levels

  12 Weeks

• Change in time with sensor glucose in tight target range [3.9-7.8 mmol/L]

  12 Weeks

• Change in fasting plasma glucose levels

  12 Weeks

• Change in body weight

  12 Weeks

Other Outcomes (15)

• Change in incretin effect

  12 Weeks

• Change in gastric emptying

  12 Weeks

• Change in glucose rate of appearance

  12 Weeks

Study Arms (3)

Menopausal Hormone Therapy

OTHER

Estradot®: 50 micrograms/24h, transdermal patch E2; Utrogestan®\*: once daily 200mg of micronized progesterone (in women with intact uterus\*)

Drug: Menopausal Hormone Therapy

GLP-1 Receptor Agonist

ACTIVE COMPARATOR

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

Drug: GLP-1 Receptor Agonist

Combined Menopausal Hornome Therapy and GLP-1 Receptor Agonist

EXPERIMENTAL

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)

Drug: GLP-1 Receptor Agonist; Drug: Menopausal Hormone Therapy

Interventions

GLP-1 Receptor Agonist DRUG

Wegovy®

Also known as: Semaglutide

Combined Menopausal Hornome Therapy and GLP-1 Receptor Agonist; GLP-1 Receptor Agonist

Menopausal Hormone Therapy DRUG

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

Also known as: Estradiol, Micronized Progesterone

Combined Menopausal Hornome Therapy and GLP-1 Receptor Agonist; Menopausal Hormone Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lia Bally: lead

Study Sites (1)

University Hospital Bern

Bern, 3010, Switzerland

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

semaglutide; Hormone Replacement Therapy; Estradiol; Progesterone

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnenediones; Pregnenes; Pregnanes; Corpus Luteum Hormones; Progesterone Congeners

Study Officials

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

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

+41 31 632 36 77; lia.bally@insel.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med. et phil.

Model Details: All efficacy outcomes will be compared primarily between the combined GLP-1RA + MHT and the GLP-1RA only regimen. The third arm (MHT only) will allow exploring mechanistic effects of MHT-mediated restoration of E2 levels on glucose and energy homeostasis and to assess benefits of combined GLP-1RA + MHT, compared to MHT alone, on haemostatic biomarkers.

Study Record Dates

• First Submitted: November 28, 2024
• First Posted: December 4, 2024
• Study Start: February 18, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: March 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: IPD will be made availabe starting 12 month after publication of trial results.
• Access Criteria: Ethics approval, as applicable under Swiss legislation, will need to be obtained by those requesting the data. Additionally, a data transfer and processing agreement must be in place to ensure compliance with data protection regulations.

Locations

CH (1)