A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral LY3502970 Compared With Placebo in Adult Participants With Obesity or Overweight and Type 2 Diabetes (ATTAIN-2)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,613
- 试验地点
- 270
- 主要终点
- Mean Percent Change from Baseline in Body Weight
研究概览
简要总结
This study will investigate the safety and efficacy of once daily oral treatment with orforglipron compared with placebo on body weight in adult participants with obesity or overweight and type 2 diabetes. The study will last about 77 weeks and may include up to 22 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
- Double (Participant, Investigator)
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 a body mass index (BMI) ≥27.0 kilogram/square meter (kg/m²).
- •Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight.
- •Have a diagnosis of Type 2 Diabetes (T2D), with HbA1c ≥7% (≥53 mmol/mol) to ≤10% (86 mmol/mol) and are on stable treatment for T2D for at least 90 days prior to screening, consisting of:
- •either diet/exercise alone or
- •up to 3 oral antihyperglycemic medications (excluding dipeptidyl peptidase IV inhibitors (DPP-4i) or glucagon-like peptide-1 (GLP-1) receptor agonists (RA).
排除标准
- •Have Type 1 Diabetes (T1D), history of ketoacidosis or hyperosmolar state/coma, or any other types of diabetes except T2D.
- •Have a self-reported change in body weight >5 kg (11 pounds) within 90 days prior to screening.
- •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 family (first-degree relative) or personal history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia 2 (MEN2) syndrome.
- •Have had a history of chronic or acute pancreatitis.
研究组 & 干预措施
Placebo
Participants received matching placebo capsule orally once daily (QD). Treatment was initiated with placebo corresponding to 1 milligram (mg) equivalent to Orforglipron, with dose escalation every 4 weeks to maintain blinding, and was continued through Week 72, unless dose modification was required.
干预措施: Placebo (Drug)
6 mg Orforglipron QD
Participants received oral orforglipron capsule once daily. Treatment was initiated at 1 mg once daily, with dose escalation every 4 weeks to a target dose of 6 mg, which was maintained through Week 72, unless dose modification was required.
干预措施: Orforglipron (Drug)
36 mg Orforglipron QD
Participants received oral orforglipron capsule once daily. Treatment was initiated at 1 mg once daily, with dose escalation every 4 weeks to a target dose of 36 mg, which was maintained through Week 72, unless dose modification was required.
干预措施: Orforglipron (Drug)
12 mg Orforglipron QD
Participants received oral orforglipron capsule once daily. Treatment was initiated at 1 mg once daily, with dose escalation every 4 weeks to a target dose of 12 mg, which was maintained through Week 72, unless dose modification was required.
干预措施: Orforglipron (Drug)
结局指标
主要结局
Mean Percent Change from Baseline in Body Weight
时间窗: Baseline, Week 72
Percent Change From Baseline in Body Weight
时间窗: Baseline, Week 72
Values represented under Least Squares (LS) Mean are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed-model repeated measures (MMRM) for post-baseline measures with region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral antihyperglycemic medications (AHMs) classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured.
次要结局
- Mean Change from Baseline in Waist Circumference(Baseline, Week 72)
- Mean Change from Baseline in Hemoglobin A1c (HbA1c) %(Baseline, Week 72)
- Mean Change from Baseline in Fasting Glucose(Baseline, Week 72)
- Mean Change from Baseline in Systolic Blood Pressure (SBP)(Baseline, Week 72)
- Mean Change from Baseline in Fasting Triglycerides(Baseline, Week 72)
- Mean Percent Change from Baseline in Fasting non-High-Density Lipoprotein (HDL) Cholesterol(Baseline, Week 72)
- Mean Percent Change from Baseline in Fasting Insulin(Baseline, Week 72)
- Mean Change from Baseline in Diastolic Blood Pressure (DBP)(Baseline, Week 72)
- Mean Change from Baseline in Short Form 36 Version 2 Health Survey Acute Form (SF-36v2) Domain Scores(Baseline, Week 72)
- Percentage of Participants Who Achieved With Greater Than or Equal to (≥) 5% Body Weight Reduction From Baseline(Baseline to Week 72)
- Percentage of Participants Who Achieved ≥10% Body Weight Reduction From Baseline(Baseline to Week 72)
- Percentage of Participants Who Achieved ≥15% Body Weight Reduction From Baseline(Baseline to Week 72)
- Change From Baseline in Waist Circumference(Baseline, Week 72)
- Change From Baseline in Hemoglobin A1c (HbA1c) %(Baseline, Week 72)
- Change From Baseline in Fasting Serum Glucose (FSG)(Baseline, Week 72)
- Percentage of Participants Who Achieved Hemoglobin A1c (HbA1c) Target Value (<6.5%)(Baseline to Week 72)
- Percentage of Participants Who Achieved Hemoglobin A1c (HbA1c) Target Value (<7.0%)(Baseline to Week 72)
- Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)(Baseline, Week 72)
- Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)(Baseline, Week 72)
- Percent Change From Baseline in Fasting Insulin(Baseline, Week 72)
- Percent Change From Baseline in Non-High-Density Lipoprotein (Non-HDL) Cholesterol (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)(Baseline, Week 72)
- Percent Change From Baseline in Triglycerides (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)(Baseline, Week 72)
- Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) Scores (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)(Baseline, Week 72)