Effects of Single Doses of Liraglutide and Dapagliflozin on Hyperglycemia and Ketogenesis in Type 1 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Difference in Ketone Bodies Formation After Single Dose of Liraglutide and Dapagliflozin
研究概览
简要总结
- To compare levels of ketone bodies (beta-hydroxybutyrate and acetoacetate) in plasma and urine following a single dose treatment of either liraglutide 1.8mg, dapagliflozin 10mg or placebo in insulinopenic state.
- To compare plasma levels of free fatty acid, glucagon, hs-CRP, Ll-6 and IL-1 before and after administration of liraglutide/placebo.
详细描述
Diabetic ketoacidosis is an important cause of mortality and morbidity in type 1 patients. The decreased ratio of insulin to glucagon in insulin deficient subjects promotes ketogenesis. In patients with type 1 diabetes, the suppressive effect of hyperglycemia and the paracrine inhibitory effect of insulin and GABA from the β cell on α cell are absent. Thus, plasma glucagon concentrations are elevated and in combination with insulin deficiency, lead to lipolysis, increased plasma FFA concentrations and an increased fatty acid supply to the liver. Thus, both fatty acid oxidation and ketogenesis are enhanced.
Our recent work has shown that liraglutide, a GLP 1 agonist, improves glycemic control and reduces glycemic excursions in patients with type 1 diabetes within a few days of the initiation of treatment.
With this background, the investigators hypothesize that suppression of glucagon with liraglutide in patients with type 1 diabetes may protect them from lipolysis, increased bio-availability of FFAs, ketogenesis and ketoacidosis.
It is essential to investigate this area further as there are no prior studies that have investigated the acute effects of liraglutide on FFAs or ketogenesis. This study will be the first randomized controlled prospective study investigating the effect of liraglutide on ketogenesis. Also, it would be important to measure the mediators of inflammation at the same time to investigate whether there is a concomitant changes of inflammatory factors in parallel with the lipolysis and ketogenesis.
After the screening visit, subjects who meet the inclusion and exclusion criteria will be randomized to receive a single dose of either liraglutide, dapagliflozin or placebo and will be monitored for a total of 8 hours.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 1 Diabetes on continuous subcutaneous insulin infusion (CSII, also known as insulin pump).
- •Undetectable c peptide (c-peptide < 0.1 ng/ml).
- •HbA1c of less than or equal to 8.5%.
- •Age 18-75 inclusive
排除标准
- •Type 1 diabetes for less than 12 months
- •Coronary event/ procedure (MI, Unstable angina, CABG, PCI) in the last four weeks
- •Hepatic disease (Transaminase > 3 times normal) or Cirrhosis
- •Renal impairment (serum eGFR <30ml/min/1.73m2)
- •HIV or Hepatitis B or C positive status
- •History of pancreatitis, i.e., history of gallstones, alcohol abuse and hypertriglyceridemia
- •Inability to give informed consent
- •History of Gastroparesis
- •Personal or Family History of medullary thyroid carcinoma or MEN 2 syndrome
- •Hypertriglyceridemia (>500 mg/dl).
- •Those with history of bladder cancer , diabetic ketoacidosis
研究组 & 干预措施
liraglutide 1.8 mg
single dose of Victoza ( liraglutide) 1.8 mg
干预措施: Victoza (Drug)
Placebo
Single dose of placebo
干预措施: Placebo (Drug)
Dapagliflozin
Single dose of Dapagliflozin 10 mg oral tablet
干预措施: Dapagliflozin 10mg Tab (Drug)
结局指标
主要结局
Difference in Ketone Bodies Formation After Single Dose of Liraglutide and Dapagliflozin
时间窗: 8 hours
To compare levels of ketone bodies beta-hydroxybutyrate in plasma following a single dose treatment of either liraglutide 1.8mg,dapagliflozin 10mg or placebo in insulinopenic state.
次要结局
- Change in Glucagon Levels.(8 hours)
- Change in Free Fatty Acid (FFA) Concentrations(8 hours)
- Change in Ghrelin Concentrations(8 Hours)
研究者
Paresh Dandona
Distinguished Professor
University at Buffalo