A Phase 3, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Oral Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin (ACHIEVE-3)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,698
- 试验地点
- 261
- 主要终点
- Change from Baseline in Hemoglobin A1c (HbA1c)
研究概览
简要总结
The main purpose of this study is to assess efficacy and safety of orforglipron compared with oral semaglutide in participants with Type 2 diabetes and inadequate glycemic control with metformin.The study will last around 61 weeks.
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
- •Have Type 2 Diabetes
- •Have HbA1c ≥7.0% (53 mmol/mol) to ≤10.5% (91 mmol/mol), as determined by the central laboratory at screening.
- •Have been on stable diabetes treatment with metformin ≥1500 milligram (mg)/day during the 90 days prior to screening and maintained through randomization.
- •Are of stable body weight (±5%) for at least 90 days prior to screening and agree to not initiate an intensive diet or exercise program during the study with the intent of reducing body weight, other than the lifestyle and/or dietary measures for diabetes treatment
排除标准
- •Have Type 1 Diabetes
- •Are currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema, for example, laser photocoagulation or intravitreal injections of anti-vascular endothelial growth factor inhibitors.
- •Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization.
- •Have a New York Heart Association functional classification IV congestive heart failure.
- •Have an estimated glomerular filtration rate (eGFR) <45 milliliter/minute (mL/min)/1.73 square meter (m²) or lower than the country-specific threshold for discontinuing metformin therapy per local label as determined by the central laboratory at screening.
- •Have a serum calcitonin level of ≥35 nanogram/Liter (ng/L), as determined by the central laboratory at screening.
- •Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years.
研究组 & 干预措施
12 mg Orforglipron
Participants initiated treatment with a 1 mg once-daily oral dose of orforglipron and increased the dose every 4 weeks until the targeted dose of 12 mg once-daily was reached, after which this dose was to be continued for the remainder of the 52-week treatment period.
干预措施: Orforglipron (Drug)
36 mg Orforglipron
Participants initiated treatment with a 1 mg once-daily oral dose of orforglipron and increased the dose every 4 weeks until the targeted dose of 36 mg once-daily was reached, after which this dose was to be continued for the remainder of the 52-week treatment period.
干预措施: Orforglipron (Drug)
14 mg Semaglutide
Participants initiated treatment with a 3 mg once-daily oral dose of semaglutide and increased the dose every 4 weeks until the targeted dose of 14 mg once-daily was reached, after which this dose was to be continued for the remainder of the 52-week treatment period.
干预措施: Semaglutide (Drug)
7 mg Semaglutide
Participants initiated treatment with a 3 mg once-daily oral dose of semaglutide and increased the dose every 4 weeks until the targeted dose of 7 mg once-daily was reached, after which this dose was to be continued for the remainder of the 52-week treatment period.
干预措施: Semaglutide (Drug)
结局指标
主要结局
Change from Baseline in Hemoglobin A1c (HbA1c)
时间窗: Baseline, Week 52
Change From Baseline in Hemoglobin A1c (HbA1c) [Non-inferiority of 36 mg Orforglipron Versus 14 mg Semaglutide and 12 mg Orforglipron Versus 7 mg Semaglutide]
时间窗: Baseline, Week 52
* HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. * LS mean was analysed by mixed model repeated measures (MMRM) model with Country + Baseline\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%).
次要结局
- Percentage of Participants Who Achieved Weight Loss of ≥5%(Week 52)
- Change from Baseline in Diastolic Blood Pressure (DBP)(Baseline, Week 52)
- Percentage of Participants Who Achieved HbA1c <5.7% (39 mmol/mol)(Week 52)
- Change from Baseline in Fasting Serum Glucose(Baseline, Week 52)
- Change from Baseline in Daily Average 7-point Self-monitored Blood Glucose (SMBG)(Baseline, Week 52)
- Percentage of Participants Who Achieved HbA1c ≤6.5% (48 mmol/mol)(Week 52)
- Percentage Change from Baseline in Body Weight(Baseline, Week 52)
- Change from Baseline in Body Weight(Baseline, Week 52)
- Change from Baseline in HbA1c(Baseline, Week 52)
- Percentage of Participants Who Achieved HbA1c <7.0% 53 millimole/mole (mmol/mol)(Week 52)
- Percentage of Participants Who Achieved Weight Loss of ≥10%(Week 52)
- Percentage of Participants Who Achieved Weight Loss of ≥15%(Week 52)
- Change from Baseline in Systolic Blood Pressure (SBP)(Baseline, Week 52)
- Percentage Change from Baseline in Total Cholesterol(Baseline, Week 52)
- Percentage Change from Baseline in Very Low Density Lipoprotein (VLDL)-Cholesterol(Baseline, Week 52)
- Percentage Change from Baseline in Triglycerides(Baseline, Week 52)
- Change from Baseline in Short Form 36 Version 2 (SF-36-v2) Acute Form Domain Summary Scores(Baseline, Week 52)
- Percentage Change from Baseline in High Density Lipoprotein (HDL)-Cholesterol(Baseline, Week 52)
- Percentage Change from Baseline in Low Density Lipoprotein (LDL)-Cholesterol(Baseline, Week 52)
- Percentage Change from Baseline in Non-HDL-Cholesterol(Baseline, Week 52)
- Percent Change From Baseline in Total Serum Cholesterol(Baseline, Week 52)
- Change From Baseline in Hemoglobin A1c (HbA1c) [Non-inferiority of 12 mg Orforglipron Versus 14 mg Semaglutide, Superiority of 12 mg and 36 mg Orforglipron Versus 7 mg and 14 mg Semaglutide](Baseline, Week 52)
- Percentage of Participants Who Achieved HbA1c <7.0% [53 Millimoles/Mole (mmol/Mol)](Week 52)
- Percentage of Participants Who Achieved HbA1c <=6.5% (48 mmol/Mol)(Week 52)
- Percentage of Participants Who Achieved HbA1c <5.7% (39 mmol/Mol)(Week 52)
- Percent Change From Baseline in Body Weight(Baseline, Week 52)
- Change From Baseline in Body Weight(Baseline, Week 52)
- Change From Baseline in Fasting Serum Glucose(Baseline, Week 52)
- Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose (SMBG)(Baseline, Week 52)
- Percentage of Participants Who Achieved Weight Loss of >=5%(Week 52)
- Percentage of Participants Who Achieved Weight Loss of >=10%(Week 52)
- Percentage of Participants Who Achieved Weight Loss of >=15%(Week 52)
- Change From Baseline in Systolic Blood Pressure (SBP)(Baseline, Week 52)
- Change From Baseline in Diastolic Blood Pressure (DBP)(Baseline, Week 52)
- Percent Change From Baseline in Serum Low Density Lipoprotein (LDL) Cholesterol(Baseline, Week 52)
- Percent Change From Baseline in Serum Non High Density Lipoprotein (Non-HDL) Cholesterol(Baseline, Week 52)
- Percent Change From Baseline in Serum Triglycerides(Baseline, Week 52)
- Percent Change From Baseline in Serum High Density Lipoprotein (HDL) Cholesterol(Baseline, Week 52)
- Percent Change From Baseline in Serum Very Low Density Lipoprotein (VLDL) Cholesterol(Baseline, Week 52)
- Change From Baseline in Short Form 36 Version 2 (SF-36-v2) Acute Form (Physical Component and Mental Component Scores)(Baseline, Week 52)