How GLP-1 Analogues Prevent Steroid-Induced Diabetes
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
- Difference in Glucose tolerance
研究概览
简要总结
TITLE: How GLP-1 Analogues prevent steroid-induced diabetes (The GAPSID Study)
DESIGN: A double-blind study evaluating how GLP-1 analogues, compared with metformin, prevent hyperglycaemia in response to a 7-day course of dexamethasone (DEX) 6 mg once daily. This is a mechanistic experimental medicine study.
AIMS: To evaluate the mechanisms by which GLP-1 analogues reduce steroid-induced hyperglycaemia compared to metformin.
OUTCOME MEASURES:
- Primary: Glucose tolerance in response to standardised mixed meal test (MMT) lasting for 240 minutes, measured in all participants at baseline and on day 7 DEX.
- Secondary: Indices of insulin resistance (M-value), beta-cell function (acute insulin response to glucose) and disposition, as measured by a combined IV glucose tolerance test and hyperinsulinaemic-euglycaemic clamp, performed at baseline and on day 7 DEX.
- Exploratory: Tissue specific changes in adipose AMPK determined from adipose and muscle biopsies, taken from a subset of approximately 8 individuals in each group.
ELIGIBILITY: People living with pre-diabetes or lifestyle controlled diabetes
STUDY DURATION: This study will take place over 3 weeks for each partcipant. Study procedures include 10 days of baseline continuous glucose monitoring (CGM) followed by 7 days of dexamethasone with GLP-1, metformin or placebo. Participants will attend a follow-up visit 3-5 days after completing the 7-day course of study drug. The study will run over a period of 3 years.
ANTICIPATED IMPACT: Mechanistic evidence for the use of GLP-1 analogues, compared with metformin, in the treatment of steroid-induced diabetes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults ≥ 18 years;
- •Male or female;
- •Pre-diabetes (HbA1c ≥42 and <47 mmol/mol, or lifestyle-controlled diabetes (HbA1c ≥48 and ≤52 mmol/mol); measurements within range on two separate occasions ≥90 days apart)
- •Body mass index ≥22.5 kg/m2
排除标准
- •Prior treatment with any diabetes medication within 90 days;
- •Current or planned pregnancy, or current breastfeeding;
- •Previous treatment with GC (topical, oral, injected) within 30 days or 90 days for extended-release injected GCs (e.g. Depo-Medrone);
- •Continuing requirement for GC treatment (e.g. for steroid replacement, chronic inflammatory or immunological condition);
- •Treatment with medications altering DEX pharmacokinetics (e.g. phenytoin, carbamazepine, ritonavir).
- •History of pancreatitis, renal disease (eGFR <30), severe hepatic impairment, gallbladder disorders, or GI disease (e.g. IBD), heart failure, history of medullary thyroid cancer (MTC), or previous skin reactions.
- •History of bleeding disorders of anticoagulant therapies (exclusion from the biopsy substudy only)
- •History of giving blood or having taken part in another non-related study in the last three months
- •History of any other medical, psychological condition, or use of any medications, which, in the opinion of the investigators, would either interfere with the study or compromise the safety of the participant.
研究组 & 干预措施
Once daily semaglutide
Once daily semaglutide 3 mg (uptitrated to 3 mg twice daily after two days).
干预措施: Semaglutide Oral Product (Drug)
- Metformin
Metformin modified release tablets (500mg once daily for the first two days, then 500 mg twice daily).
干预措施: Metformin Oral Tablet (Drug)
Placebo
Placebo tablets
干预措施: Placebo (Drug)
结局指标
主要结局
Difference in Glucose tolerance
时间窗: Through study completion, on day 7 dexamethasone and study medication
Glucose tolerance as measured by glucose area under the curve (AUC), in response to standardised mixed meal test (MMT) lasting for 240 minutes. This will be measured in all participants at baseline and at the end of the study medication period (after 7 days of dexamethasone and study medication).
次要结局
- Difference in insulin secretion(Day 6 of dexamethasone and study medication)
- Difference in insulin sensitivity(Day 6)