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

ConditionsMenopause Type 2 Diabetes

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexFemale

Age18+

SponsorLia Bally

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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%)

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

GLP-1 Receptor Agonist
Drug
Wegovy®
Menopausal Hormone Therapy
Drug
Estradot® and Utrogestan®\* (in women with intact uterus\*)

Treatment groups

96 Participants

are divided into 3 treatment groups

Group A: Menopausal Hormone TherapyOther 1 intervention

Group B: GLP-1 Receptor AgonistActive comparator 1 intervention

Group C: Combined Menopausal Hornome Therapy and GLP-1 Receptor AgonistExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

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.

Time frame

12 Weeks

Secondary outcomes

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

Change in postprandial plasma glucose exposure from Baseline (Visit 1a) to Visit 2a. Postprandial glucose exposure will be quantified by the area under the plasma glucose concentration curve from glucose intake (T0) until 240 minutes following glucose intake. The resulting values will be normalized to the duration of the experiment and reported in mmol/L.

Time frame

12 Weeks

Change in average sensor glucose levels

The change will be quantified as the difference in average sensor glucose levels from the Baseline assessment period (14 days prior to end of Visit 1a) to the last 14 days of the intervention period (i.e., the 14 days before Visit 2a) (units: mmol/L).

Time frame

12 Weeks

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

The change, measured in percentage points, will be quantified as the difference in the percentage of time with sensor glucose in the tight target range \[3.9-7.8 mmol/L\] from the Baseline assessment period (14 days prior to end of Visit 1a) to the last 14 days of the intervention period (i.e., the 14 days before Visit 2a).

Time frame

12 Weeks

Change in fasting plasma glucose levels

The change will be quantified as the difference in fasting plasma glucose levels from Baseline (Visit 1a) to Visit 2a (units: mmol/L).

Time frame

12 Weeks

Other outcomes

Change in incretin effect

Incretin effect (OGTT-IIGI difference in the insulin secretion AUC). The change in OGTT-IIGI insulin secretion AUC from Visit 1 (Visit 1a and Visit 1b) to Visit 2 (Visit 2a and Visit 2b) will be evaluated (units: percentage points). The direct incretin effect will only be assessed in the MHT only arm.

Time frame

12 Weeks

Change in gastric emptying

The change in gastric emptying from Baseline (Visit 1a) to Visit 2a will be quantified by the half-emptying time (units: min). Gastric emptying will be calculated from the 13CO2 enrichment in breath samples collected during the OGTT.

Time frame

12 Weeks

Change in glucose rate of appearance

The change in glucose rate of appearance from Baseline (Visit 1a) to Visit 2a will be evaluated (units: percentage points). Glucose rate of appearance will be quantified using the Oral Minimal Model Method on the OGTT data.

Time frame

12 Weeks

Change in beta-cell function

The change in beta-cell function from Baseline (Visit 1a) to Visit 2a will be evaluated (units: 10e-9/min). Beta-cell function will be quantified using the Oral Minimal Model Method on the OGTT data.

Time frame

12 Weeks

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Lia Bally

Lead sponsor

Insel Gruppe AG, University Hospital Bern

Sponsor institution

Source ClinicalTrials.gov

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