MenopauseDECLARED-CTNCT06715514
Menopausal Hormone Therapy, GLP-1 Agonists, and Glucose and Energy Homeostasis in Postmenopausal Women With Overweight/Obesity and Impaired Glucose Homeostasis
A study testing GLP-1 Receptor Agonist and Menopausal Hormone Therapy in people with Menopause and Type 2 Diabetes, run by Lia Bally at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Menopause, Type 2 Diabetes
- What is being tested?
- GLP-1 Receptor Agonist and Menopausal Hormone Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteSwitzerland
- Study dates
- 18 Feb 2025to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Individuals fulfilling at enrolment all of the following inclusion criteria are eligible for the study:
- 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
The presence of any of the following exclusion criteria will lead to exclusion of the individuals:
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Combined Menopausal Hormone Therapy and GLP-1 Receptor Agonist Therapy on Glucose and Energy Homeostasis in Early Postmenopausal Women With or at Risk of Diabetes
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.
Read the 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
- Being tested
- GLP-1 Receptor Agonist, Menopausal Hormone Therapy
- Keywords
- Diabetes, Menopause, Menopausal Hormone Therapy, Womens Health, Randomized Controlled Trial, GLP-1 receptor agonist
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GLP-1 Receptor AgonistDrug
Also called Semaglutide
Wegovy®
Menopausal Hormone TherapyDrug
Also called Estradiol, Micronized Progesterone
Estradot® and Utrogestan®* (in women with intact uterus*)
| Study group | Role | What they receive |
|---|---|---|
| Menopausal Hormone Therapy | Other | Estradot®: 50 micrograms/24h, transdermal patch E2;
Utrogestan®*: once daily 200mg of micronized progesterone (in women with intact uterus*) Receives: 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 Receives: 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) Receives: Drug: GLP-1 Receptor Agonist; Drug: Menopausal Hormone Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 Weeks
Secondary outcomes (14)
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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 12 Weeks
Change in body weight
The change from Baseline (Visit 1a) to Visit 2a will be evaluated (units: kg).
Measured: 12 Weeks
Change in body fat percentage
The change in percentage of body fat from Baseline (Visit 1a) to Visit 2a will be evaluated (units: percentage points). The percentage of body fat will be obtained from BIA measurements.
Measured: 12 Weeks
Change in non-HDL cholesterol
The change in non-HDL cholesterol from Baseline (Visit 1a) to Visit 2a will be evaluated (units mmol/L). Non-HDL cholesterol will be quantified as the difference between total cholesterol and HDL cholesterol.
Measured: 12 Weeks
Change in systolic blood pressure
The change in systolic blood pressure from Baseline (Visit 1a) to Visit 2a will be evaluated (units: mmHg).
Measured: 12 Weeks
Change in liver fat (controlled attenuation parameter)
The change in the controlled attenuation parameter from Baseline (Visit 1a) to Visit 2a will be evaluated (units: dB/m). Liver fat will be quantified using transient elastography.
Measured: 12 Weeks
Change in whole-body insulin sensitivity
The change in whole-body insulin sensitivity from Baseline (Visit 1a) to Visit 2a will be evaluated (units: 10e-5 dL/(kg*min) per pmol/L). Whole-body insulin sensitivity will be quantified using the Oral Glucose Minimal Model method on the OGTT data.
Measured: 12 Weeks
Change in quality of life
The change in the quality of life from Baseline (Visit 1a) to Visit 2a will be evaluated (units: arbitrary units). Quality of life will be assessed using the total score of the EQ-5D-5L questionnaire.
Measured: 12 Weeks
Change in postmenopausal symptoms burden
The change in the postmenopausal symptoms burden from Baseline (Visit 1a) to Visit 2a will be evaluated (units: arbitrary units). Postmenopausal symptom burden will be assessed using the total score of the Menopausal Rating Scale (MRS-II).
Measured: 12 Weeks
Change in frequency of vasomotor symptoms
The change in the frequency of vasomotor symptoms from Baseline (Visit 1a) to Visit 2a will be evaluated (units: number per day). The frequency of vasomotor symptoms will be assessed using an electronic diary during 24 hours prior to Visit 1a and Visit 2a.
Measured: 12 Weeks
Change in intensity of vasomotor symptoms
The change in the intensity of vasomotor symptoms from Baseline (Visit 1a) to Visit 2a will be evaluated (units: intensity per episode).The intensity of vasomotor symptoms will be assessed using the intensity scale for hot flashes in the Menopausal Rating Scale (MRS-II). It will be recorded in an electronic diary during 24 hours prior to Visit 1a and Visit 2a.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2024
- Study start18 Feb 2025
- Primary completion17 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MenopauseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lia Bally
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Lia Bally, Insel Gruppe AG, University Hospital Bern
- Investigators
- Prof. Dr. med. et Dr. phil.Lia Bally, Principal investigator, Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06715514
- Sponsor's protocol ID
- DECLARED-CT
- Other IDs
- 10000574, 2024-01882
- Acronym
- DECLARED-CT
- Status last verified
- Aug 2026
- First submitted
- 28 Nov 2024
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data (IPD) will be made available upon reasonable request to the principal investigator.
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Combined Menopausal Hormone Therapy and GLP-1 Receptor Agonist Therapy on Glucose and Energy Homeostasis in Early Postmenopausal Women With or at Risk of Diabetes
- ClinicalTrials.gov ID
- NCT06715514
- Acronym / sponsor ID
- DECLARED-CT / DECLARED-CT
- Conditions
- Menopause, Type 2 Diabetes
- Keywords
- Diabetes, Menopause, Menopausal Hormone Therapy, Womens Health, Randomized Controlled Trial, GLP-1 receptor agonist
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Lia BallyUniversity, hospital or other
- Study start
- 18 Feb 2025 (actual)
- Primary completion
- 17 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 4 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Menopausal Hormone Therapy | Other | Drug: Menopausal Hormone TherapyEstradot®: 50 micrograms/24h, transdermal patch E2; Utrogestan®*: once daily 200mg of micronized progesterone (in women with intact uterus*) |
| GLP-1 Receptor Agonist | Active comparator | Drug: GLP-1 Receptor AgonistWegovy®: Semaglutide injected once weekly, starting dose 0.25mg, with dose increments every four weeks reaching the maintenance dose of 1mg after eight weeks |
| Combined Menopausal Hornome Therapy and GLP-1 Receptor Agonist | Experimental | Drug: GLP-1 Receptor Agonist, Drug: Menopausal Hormone TherapyWegovy®: 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GLP-1 Receptor AgonistAlso: SemaglutideWegovy® | Drug | Combined Menopausal Hornome Therapy and GLP-1 Receptor Agonist, GLP-1 Receptor Agonist |
| Menopausal Hormone TherapyAlso: Estradiol, Micronized ProgesteroneEstradot® and Utrogestan®* (in women with intact uterus*) | Drug | Combined Menopausal Hornome Therapy and GLP-1 Receptor Agonist, Menopausal Hormone Therapy |
Primary outcome
Change in HbA1C
Time frame: 12 Weeks
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.
14 secondary outcomes
Change in postprandial plasma glucose exposure during the OGTT (AUC plasma glucose concentration)
Time frame: 12 Weeks
Change in average sensor glucose levels
Time frame: 12 Weeks
Change in time with sensor glucose in tight target range [3.9-7.8 mmol/L]
Time frame: 12 Weeks
Change in fasting plasma glucose levels
Time frame: 12 Weeks
Change in body weight
Time frame: 12 Weeks
Change in body fat percentage
Time frame: 12 Weeks
Change in non-HDL cholesterol
Time frame: 12 Weeks
Change in systolic blood pressure
Time frame: 12 Weeks
Change in liver fat (controlled attenuation parameter)
Time frame: 12 Weeks
Change in whole-body insulin sensitivity
Time frame: 12 Weeks
Change in quality of life
Time frame: 12 Weeks
Change in postmenopausal symptoms burden
Time frame: 12 Weeks
Change in frequency of vasomotor symptoms
Time frame: 12 Weeks
Change in intensity of vasomotor symptoms
Time frame: 12 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) will be made available upon reasonable request to the principal investigator.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof. Dr. med. et Dr. phil.Lia Bally principal investigator
Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GLP-1 Receptor Agonist and Menopausal Hormone Therapy in people with Menopause and Type 2 Diabetes, run by Lia Bally at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in HbA1C (time frame: 12 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.