Efficacy and Safety of LY3298176 Once Weekly Versus Insulin Glargine in Patients With Type 2 Diabetes and Increased Cardiovascular Risk (SURPASS-4)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,002
- 试验地点
- 208
- 主要终点
- Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
研究概览
简要总结
The purpose of the trial is to assess the efficacy and safety of tirzepatide taken once a week to insulin glargine taken once daily in participants with type 2 diabetes and increased cardiovascular risk. The study will last about 108 weeks and may include up to 30 visits.
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
- None
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
- •Participants must:
- •Have been diagnosed with type 2 diabetes mellitus (T2DM)
- •Have HbA1c between ≥7.5% and ≤10.5%
- •Be on stable treatment with unchanged dose of at least 1 and no more than 3 types of oral antihyperglycemic drugs, which may only include metformin, SGLT-2 inhibitors, and/or sulfonylureas for at least 3 months before screening
- •Have increased risk for cardiovascular (CV) events
- •Be of stable weight (± 5%)
- •Have a BMI ≥25 kilograms per meter squared (kg/m2) at screening
- •Exclusion Criteria
- •Participants must not:
- •Have type 1 diabetes mellitus
- •Have had chronic or acute pancreatitis any time prior to study entry
- •Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring immediate or urgent treatment
- •Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss
- •Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) enzyme level >3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Participants with nonalcoholic fatty liver disease (NAFLD) are eligible for participation in this trial only if there ALT level is ≤3.0 the ULN for the reference range
- •Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months
- •Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2
- •Have been taking any other diabetes medicines other than metformin, SGLT-2 inhibitors, and/or sulfonylureas during the last 3 months
- •Have been taking weight loss drugs, including over-the-counter medications during the last 3 months
排除标准
- 未提供
研究组 & 干预措施
5 mg Tirzepatide
5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
干预措施: Tirzepatide (Drug)
10 mg Tirzepatide
10 mg tirzepatide administered SC once a week.
干预措施: Tirzepatide (Drug)
15 mg Tirzepatide
15 mg tirzepatide administered SC once a week.
干预措施: Tirzepatide (Drug)
Insulin Glargine
Insulin glargine administered SC once a day. Doses were individualized and titrated according to protocol-defined targets.
The starting dose of insulin glargine was 10 IU/day at bedtime, titrated to a FBG <100 mg/dL, following a treat-to-target (TTT) algorithm.
干预措施: Insulin Glargine (Drug)
结局指标
主要结局
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
时间窗: Baseline, Week 52
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model for post-baseline measures: Variable = Baseline + Pooled Country + Baseline sodium-glucose co-transporter-2 inhibitor (SGLT-2i) use Flag (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
次要结局
- Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia(Baseline through Week 52)
- Change From Baseline in Body Weight(Baseline, Week 52)
- Change From Baseline in Fasting Serum Glucose(Baseline, Week 52)
- Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve From Zero to Tau (AUC 0-Tau) of Tirzepatide(1 to 24 hours, 24 to 96 hours, or 120 to 168 hours post dose of Week 7, 15, 23, 35)
- Change From Baseline in HbA1c (5 mg)(Baseline, Week 52)
- Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values(Baseline, Week 52)
- Percentage of Participants With HbA1c of <7.0%(Week 52)