Gut-derived Incretin Hormones in the Pathophysiology of Type 1 Diabetes Mellitus; Effect of Metformin Treatment
试验速览
- 阶段
- 3 期
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Change in GLP-1 (glucagon like peptide) and GIP (gastric inhibitory peptide) postprandial secretion
研究概览
简要总结
Investigators aim is to conduct an RCT to study the effect of adjunct metformin treatment to insulin monotherapy in patients with type 1 diabetes, targeting the intestinal incretin secretion. The patients will be randomly allocated to metformin or placebo treatment for 4 months
详细描述
Compared to the large armamentarium of antidiabetic agents for Type 2 Diabetes Mellitus (T2DM), the insulinocentric therapeutic approach in Type 1 Diabetes Mellitus (T1DM) has distracted the scientific perspective from the rise of novel therapies. Insulin monotherapy has long overshadowed the overall hormonal dysregulation that demarcates T1DM . In specific, the significance of the gut-derived incretin hormones GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic peptide), which are implicated with glucose metabolism via the gut-pancreatic axis, has been merely addressed.
Investigators' goal in the current protocol is to delineate the glucoregulatory role of incretin hormones in T1DM and the therapeutic advantages of adjunct metformin treatment over insulin monotherapy. In the absence of such knowledge, the development of effective strategies to improve metabolic homeostasis and ameliorate complications in T1DM patients will remain problematic. The central hypothesis of the study is that metformin, as an incretin-secretagogue, will enhance postprandial incretin secretion in T1DM patients, which will be reflected in reduced glucagon secretion and improvement in glycemic volatility. Mechanistic insight will be provided through changes in specific amino acids and metabolites patterns, chronic inflammation and the microbiome composition.
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
- Double (Participant, Investigator)
盲法说明
All pills will be provided as effervescent, pre-scored 1000mg tablets, so that they may easily be dichotomized.Boxes with active drug or placebo will be covered to conceal the identity of the test article. Sponsor will provide covering materials.The unblinded designee will provide the covered boxes to the blinded nurse or blinded investigator who will dispense the pills.Participants will be given study drug diaries, which they will complete during study drug intake.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •T1DM (Diagnosis of diabetes before the age of 35 years and insulin use within 1 year of diagnosis)
- •Treatment with multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII)
排除标准
- •Any cardiovascular disease within the last 3 months
- •NYHA stage 3 or 4 heart failure
- •Uncontrolled angina
- •Liver failure [AST>135 IU/L or ALT>129IU/L (3 x the upper normal limit)] • Kidney failure or GFR<60 ml/min/1.73m2
- •Gastrointestinal disease or gastroparesis
- •Prior diagnosis of cancer within 2 years
- •Other medication that affect glucose metabolism within the last 3 months (metformin, SGLT2, GLP-1 analogues, amylin analogues, systemic glucocorticosteroids)
- •Untreated or uncontrolled thyroid disease
- •Pregnancy or breastfeeding
- •Alcohol consumption > 2-drinks per day or other substance abuse
研究组 & 干预措施
Metformin
Patients will continue with their standard insulin therapy and will additionally receive orally metformin 2gr/day.
干预措施: Metformin (Drug)
Placebo
Patients will continue with their standard insulin therapy and will additionally receive placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in GLP-1 (glucagon like peptide) and GIP (gastric inhibitory peptide) postprandial secretion
时间窗: 4 months
The primary endpoint of the study is the change in postprandial GLP-1(ng/ml) and GIP (ng/ml) secretion with metformin treatment compared to placebo.
次要结局
- Change in glycemic variability pre- and post- treatment(4 months)
- Metabolomic profile of each treatment group(4 months)
- Change in cytokine production(4 months)
- Change in endothelial dysfunction(4 months)
- Change in gene expression(4 months)
- Change in inflammatory state(4 months)
- Change in chemokine production(4 months)
- Change in matrix metalloproteinase-9 (MMP-9) levels(4 months)
- Change in gut microbiome analysis(4 months)