Glucose Metabolism in South Asian Women With IGT or IFG. DIAbetes in South Asians - DIASA 3: A 12-week Intervention Trial With Oral Antidiabetic Medication to Improve Hepatic and Whole Body Insulin Sensitivity
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Endogenous glucose production during fasting
研究概览
简要总结
This study will test the effect of four common oral anti-diabetic agents on hepatic insulin sensitivity in South Asian women with impaired glucose tolerance or impaired fasting glucose. In a 12-week, double-blind, randomized controlled intervention trial, the following drugs will be tested head-to-head: Metformin, Pioglitazone, Empagliflozin and Linagliptin. Additional, exploratory outcomes include whole body insulin sensitivity, insulin secretion and other markers of glucose and lipid metabolism, measured by the euglycemic clamp with stable isotope tracer dilution, indirect calorimetry and CT-measurements of abdominal adipose tissue compartment volumes and hepatic and pancreatic volume and attenuation.
The study is part of the DIASA - DIAbetes in South Asians - Research Programme, which aims to find ways to improve both prevention and treatment of type 2 diabetes in people of South Asian ethnicity.
详细描述
Background: South Asians (SA) have a high prevalence of type 2 diabetes (T2D). SA i Norway develop T2D approximately 10 years earlier than Nordic subjects (NO).T2D in SA is often poorly regulated with increased risk of complications.
Research hypothesis: South Asian subjects with Impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) have a high degree of hepatic insulin resistance. Treatment with certain oral antidiabetic drugs will improve hepatic insulin sensitivity more than others.
Primary objective: To assess which of four oral antidiabetic medications is most effective in improving hepatic insulin sensitivity in women of South Asian origin with IFG/IGT.
Study design: Single-center, randomized, double-blind intervention trial with 4 parallel treatment arms: 1) Metformin 2) Pioglitazone 3) Empagliflozin 4) Linagliptin.
Endogenous glucose production (EGP) and hepatic and whole body insulin sensitivity will be assessed by a 2-step euglycemic, hyperinsulinemic clamp with deuterated glucose tracer. In addition, glucose and lipid metabolism will be assessed by indirect calorimetry (IC), insulin secretion by an oral glucose tolerance test (OGTT), and fatty infiltration in liver by computer tomography (CT).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Blinded medication
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Able and willing to give informed consent
- •Woman ≥ 18 years of age
- •Of South Asian origin
- •Participated in the DIASA 1 study (i.e. has had previous gestational diabetes (GDM) in last pregnancy). A period of 3 months after the 3-year limit since childbirth after GDM is seen as acceptable for inclusion.
- •Impaired glucose tolerance (2-hour glucose value ≥7.8 and < 11.1 mmol/l) and/or impaired fasting glucose (fasting plasma glucose ≥ 6.1 and < 7.0 mmol/l) diagnosed in DIASA 1
排除标准
- •Known type 2 diabetes
- •Known type 1 diabetes
- •Fasting or 2-hour glucose values outside the inclusion criteria if the subject according to protocol needs to undergo an OGTT at baseline in DIASA 3
- •Pregnant or fully lactating at randomisation or planned during study period.
- •Not willing to practice a highly effective birth control method* prior to initial dose, during study and for 2 weeks after the last administration of study drug.
- •Concomitant use of any antidiabetic medication
- •Concomitant use of fibrates or rifampicin
- •Radiological examinations iodine containing contrast the previous week before randomisation, or planned during the study period.
- •Known serious illness such as cancer (except in situ carcinoma) during past 5 years.
- •Previous radiation therapy directed towards the pelvic area.
- •Heart failure New York Heart Association (NYHA) class I-IV.
- •Estimated glomerulus filtration rate (eGFR) < 60 ml/min/1,73m2
- •Chronic liver disease with serum levels of aspartate aminotransferase (ASAT) or alanine amino transferase (ALAT) > 5 x upper limit of normal (ULN) or known impaired liver function (INR > 1.5, Albumin < 20 g/l, Bilirubin > 20 g/l.
- •Active infectious disease at inclusion
- •Use of systemic corticosteroids > 14 days within last 3 months before inclusion
- •Hypothyroidism where substitution with levothyroxine has not been stable for the last 3 months or with thyroid stimulating hormone (TSH) outside normal limits.
- •A history of bullous pemphigoid
- •A history of acute or chronic pancreatitis
- •Previous or present acute metabolic acidosis.
- •Known hypersensitivity to any of the active ingredients or additives in the study medication or placebo capsules.
- •Macroscopic haematuria not previously examined
- •History of major surgical procedures within 3 months prior to inclusion or planned during study period.
- •Any condition which in the investigator's opinion would jeopardize the subject's safety or compliance with the protocol.
- •Birth control methods which may be considered as highly effective: Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), intrauterine hormone-releasing system ( IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence.
研究组 & 干预措施
Metformin
Metformin 500 mg x 1, morning, for 2 weeks, then Metformin 500 mg x 2, morning and evening for 10 weeks.
干预措施: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg (Drug)
Empagliflozin
Empagliflozin 10 mg x 1, morning, for 2 weeks, then Empagliflozin 10 mg morning + Placebo evening for 10 weeks.
干预措施: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg (Drug)
Linagliptin
Linagliptin 5 mg x 1, morning, for 2 weeks, then Linagliptin 5 mg morning + Placebo evening for 10 weeks.
干预措施: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg (Drug)
Pioglitazone
Pioglitazone 30 mg x 1, morning, for 2 weeks, then Pioglitazone 30 mg morning + Placebo evening for 10 weeks.
干预措施: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg (Drug)
结局指标
主要结局
Endogenous glucose production during fasting
时间窗: After 12 weeks on respective drugs
Difference between treatment arms in change from baseline to 12 weeks in endogenous glucose production during fasting measured by the deuterated glucose tracer dilution method in umol/(kg fat free mass x minutes)
次要结局
未报告次要终点
研究者
Kåre Inge Birkeland
Professor
Oslo University Hospital