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
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 96
- 试验地点
- 3
- 主要终点
- Change in HbA1C
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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)
干预措施: Menopausal Hormone Therapy (Drug)
Menopausal Hormone Therapy
Estradot®: 50 micrograms/24h, transdermal patch E2;
Utrogestan®*: once daily 200mg of micronized progesterone (in women with intact uterus*)
干预措施: Menopausal Hormone Therapy (Drug)
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
干预措施: GLP-1 Receptor Agonist (Drug)
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)
干预措施: GLP-1 Receptor Agonist (Drug)
结局指标
主要结局
Change in HbA1C
时间窗: 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.
次要结局
- 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)
- Change in body fat percentage(12 Weeks)
- Change in non-HDL cholesterol(12 Weeks)
- Change in systolic blood pressure(12 Weeks)
- Change in liver fat (controlled attenuation parameter)(12 Weeks)
- Change in whole-body insulin sensitivity(12 Weeks)
- Change in quality of life(12 Weeks)
- Change in postmenopausal symptoms burden(12 Weeks)
- Change in frequency of vasomotor symptoms(12 Weeks)
- Change in intensity of vasomotor symptoms(12 Weeks)
- Change in postprandial plasma glucose exposure during the OGTT (AUC plasma glucose concentration)(12 Weeks)
研究者
Lia Bally
Prof. Dr. med. et phil.
Insel Gruppe AG, University Hospital Bern