Acute Metabolic Effects of Tirzepatide in Type 1 Diabetes: a Phase 2 Double Blinded Placebo Controlled Clinical Trial (TIRTLE2)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 44
- 试验地点
- 3
- 主要终点
- Whole-body insulin sensitivity
研究概览
简要总结
This study will examine the effects of Tirzepatide (TZP), a glucagon-like peptide 1 (GLP1) - gastric inhibitory peptide (GIP) co-agonist, on metabolism in type 1 diabetes (T1D). Research participants with T1D will undergo measures of insulin sensitivity, and hormone levels post-meal, post-hypoglycemia and during the overnight period. These measures will be performed prior to, and after 6 weeks of treatment with TZP or placebo.
详细描述
TIRTLE2 is a phase 2 double-blinded placebo-controlled mechanistic clinical trial that extends upon the findings of TIRTLE1, a phase 2 double-blinded placebo-controlled trial (TZP 5.0mg vs placebo over 12 weeks) in T1D (trial registration: ACTRN12624000111572).
TIRTLE2 is a designed to determine whether TZP can 1) improve whole body insulin sensitivity, 2) reduce prandial glucagon secretion, 3) impacts lipolysis and growth hormone secretion overnight, and 4) determine if TZP can maintain the glucagon response to hypoglycemia. The acute effects of TZP on metabolism will be assessed after 6 weeks, to limit the degree of weight loss (indicating a role for TZP on improving metabolic physiology in T1D, beyond weight management in T1D).
To address these research aims, a single comprehensive clinical trial will be performed in 44 participants with T1D, who will receive a weekly injection of TZP 2.5mg or placebo for 6 weeks. A short treatment duration was chosen to assess if TZP offers T1D-specific benefits prior to significant weight loss.
TIRTLE2 will employ the 'gold standard' hyperinsulinemic-euglycemic and hypoglycemic clamps, in conjunction with complementary analyses of the effects of TZP on metabolism across multiple physiological states. This mechanistic study will define mechanisms by which GLP1-GIP co-agonism may uniquely provide clinical benefits in T1D during the fasting and fed states, and during hypoglycemia.
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)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age 18-65 years
- •BMI ≥ 27 kg/m2
- •HbA1c ≤ 9.0%
- •insulin delivery using an automated insulin delivery system
- •at least 2 years since diagnosis of type 1 diabetes
排除标准
- •TZP or GLP-1 receptor agonist in last 3 months; metformin or sodium glucose co-transporter 2 (SGLT2) inhibitor in the last 6 weeks; steroids, antipsychotics, immunosuppressants in the last 6 weeks.
- •Hypoglycemic unawareness or severe hypoglycemia last 6 months.
- •History of seizure disorder.
- •History of weight loss surgery.
- •eGFR <60 mL/min/1.73 m
- •Liver disease (known cirrhosis, LFTs > 3x upper limit of normal).
- •Active malignancy.
- •Pregnant, breastfeeding, planning pregnancy within 6 months, or not using adequate contraception.
- •History of cardiovascular disease, or coronary event or stroke in last 3 months
- •Hemoglobin level < 13.5 g/dL in men, < 12.0 g/dL in women
研究组 & 干预措施
Tirzepatide 2.5mg weekly
Administered subcutaneously.
干预措施: Tirzepatide 2.5mg weekly (Drug)
Placebo
Administered subcutaneously.
干预措施: Placebo injection (normal saline) (Drug)
结局指标
主要结局
Whole-body insulin sensitivity
时间窗: 6 weeks
Change in insulin sensitivity from baseline, assessed using the hyperinsulinemic-euglycemic clamp (60 mU/m2/min)
次要结局
- Prandial glucagon secretion(6 weeks)
- Glucagon response to hypoglycemia(6 weeks)
- % Time level 2 hypoglycemia(6 weeks)
- % Time level 1 hypoglycemia(6 weeks)
- Resting energy expenditure (REE)(6 weeks)
- Overnight growth hormone curve(6 weeks)
- Overnight free-fatty acids (FFA) curve(6 weeks)
- Total daily insulin dose(6 weeks)
- Total daily basal insulin dose(6 weeks)
- Total daily bolus insulin dose(6 weeks)
- % Time in Range (TIR)(6 weeks)
- % Time Below Range (TBR)(6 weeks)
- % Time level 1 hyperglycemia(6 weeks)
- % Time level 2 hyperglycemia(6 weeks)
- Glycemic variability(6 weeks)
- Gastric emptying(6 weeks)