Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes: a Randomized Open Intervention Study That Compares Empagliflozin, Pioglitazone and Semaglutide
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Changes in fat cell lipolysis after 6 months of treatment
研究概览
简要总结
People with newly diagnosed type 2 diabetes treated with metformin that have not reached their HbA1c target (42-64 mmol/mol) will be recruited to the study. If they fulfill the inclusion and none of the exclusion criteria, they will be, after signing informed consent, randomized to a six-month intervention with either pioglitazone, empagliflozin or semaglutide. Fat biopsies are obtained from the subcutaneous abdominal area before and after a hyperinsulinemic-euglycemic clamp at baseline and after six months. Participants are regularly followed during this the intervention. The overall goal is to determine how antidiabetic-drugs affect white adipose tissue cellularity and whether adipose heterogeneity impacts on drug response. The primary outcome measure is the change in fat tissue lipolysis (glycerol release in isolated fat cells after hormone stimulation) before and after treatment.
详细描述
A detailed description of the protocol has been approved by the Swedish Medical Products Agency and the study is registered as EudraCT: 2021-002367-21.
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
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •BMI 25 kg/m2 or higher
- •HbA1c 42 mmol/mol or higher
- •For fertile women, effective contraception
排除标准
- •HbA1c 65 mmol/mol or higher
- •Established cardiovascular disease and/or heart failure
- •Severe psychiatric condition
- •Active alcoholism
- •Insulin treatment
- •Anticoagulant therapy (vitamin K antagonists or equivalent)
- •Pregnancy, lactation
- •Positive GAD or IA2 antibodies
- •Low C-peptide/glucose ratio (less than 2 measured as pmol/mg per dL)
- •NT-proBNP above the upper normal reference value
- •Kidney disease
- •Liver disease or hepatic values over twice the upper reference value
- •Severe concomitant disease including ongoing cancer
研究组 & 干预措施
Pioglitazone
Pioglitazone is known to affect fat cells and is used as an active comparator. It reduces HbA1c but increase fat mass slightly. We hypothesize that pioglitazone may have particular benefits in individuals with a specific adipose cellularity.
干预措施: Pioglitazone 45 mg (Drug)
Empagliflozin
Empagliflozin reduces HbA1c and increase lipolysis possibly due to increased glucagon secretion. It also reduces fat mass weight to a minor degree.
干预措施: Empagliflozin 25 MG (Drug)
Semaglutide
Semaglutide reduces body weight, including fat mass, to a more significant degree than empagliflozin but has no known direct effects on adipose tissue.
干预措施: Semaglutide 7 MG (Drug)
结局指标
主要结局
Changes in fat cell lipolysis after 6 months of treatment
时间窗: Baseline and after six months intervention
Change in isoprenaline-induced (over basal) lipolysis in isolated fat cells
次要结局
- Changes in fat cell heterogeneity after 6 months of treatment(Baseline and after six months intervention)
研究者
Mikael Ryden
Professor, senior consultant, MD, PhD
Karolinska Institutet