Efficacy and Safety of Tirzepatide Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-1)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 2,539
- 试验地点
- 1
- 主要终点
- Mean percent change in body weight from randomization
研究概览
简要总结
This Phase 3 study evaluates the efficacy and safety of once-weekly subcutaneous tirzepatide (a dual GIP and GLP-1 receptor agonist) at 5 mg, 10 mg, or 15 mg versus placebo, each used with a reduced-calorie diet and increased physical activity, in adults without type 2 diabetes who have obesity or are overweight with weight-related comorbidities. The primary efficacy assessment is at Week 72. Participants with prediabetes at randomization may continue in an additional long-term treatment period to assess progression to type 2 diabetes and longer-term weight outcomes.
详细描述
After screening, eligible participants are randomized in a 1:1:1:1 ratio to receive tirzepatide 5 mg, 10 mg, 15 mg, or placebo once weekly by subcutaneous injection using an autoinjector. All participants receive lifestyle counseling focused on a reduced-calorie diet and increased physical activity. The main treatment period is 72 weeks. Participants identified with prediabetes at randomization can continue study treatment for up to 176 weeks (plus follow-up), allowing evaluation of longer-term weight management and time to onset/progression to type 2 diabetes. Safety is monitored throughout, including adverse events and laboratory testing.
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)
盲法说明
Participants and investigators are blinded to treatment assignment. Study drug and placebo are administered using similar autoinjector pens; randomization and drug dispensing are managed centrally via an interactive system.
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
- •BMI ≥30 kg/m², OR BMI ≥27 kg/m² with ≥1 weight-related comorbidity (e.g., hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease)
- •History of at least one unsuccessful dietary effort to lose weight (self-reported)
- •Investigator judges participant capable and willing to self-inject (or have assistance), follow lifestyle advice, maintain a diary, and complete questionnaires
- •Age ≥18 years
- •Meets protocol contraception/pregnancy criteria (as applicable) and provides written informed consent
排除标准
- •Type 1 or type 2 diabetes, history of ketoacidosis/hyperosmolar state, or screening labs diagnostic of diabetes
- •Recent significant weight change (>5 kg within 3 months prior to screening)
- •Prior/planned bariatric surgery; recent/ongoing endoscopic or device-based obesity therapies
- •Severe renal impairment (eGFR <30 mL/min/1.73 m²)
- •Clinically significant gastric emptying abnormality or chronic use of drugs that directly affect GI motility
- •History of chronic or acute pancreatitis
- •Clinically significant thyroid abnormalities at screening (e.g., TSH outside protocol range) or anticipated need to initiate thyroid replacement during study
- •Obesity due to other endocrinologic disorders (e.g., Cushing syndrome) or monogenic/syndromic obesity (e.g., MC4R deficiency, Prader-Willi syndrome)
- •Significant unstable major depressive disorder/severe psychiatric disorder, lifetime suicide attempt, or concerning suicidality screening (PHQ-9/C-SSRS criteria)
- •Uncontrolled hypertension; recent major cardiovascular events; NYHA class IV heart failure
- •Active or significant liver disease or certain elevated liver tests at screening (per protocol thresholds)
- •Elevated calcitonin above protocol thresholds; personal/family history of medullary thyroid carcinoma or MEN2
- •Active/untreated malignancy or remission <5 years (with specified exceptions)
- •Any other condition contraindicating GLP-1 receptor agonist therapy
研究组 & 干预措施
Arm 4: Placebo once weekly + lifestyle intervention
干预措施: Tirzepatide (Drug)
Arm 4: Placebo once weekly + lifestyle intervention
干预措施: Placebo (Drug)
Arm 4: Placebo once weekly + lifestyle intervention
干预措施: Reduced-calorie diet (Behavioral)
Arm 1: Tirzepatide 5 mg once weekly + lifestyle intervention
干预措施: Tirzepatide (Drug)
Arm 1: Tirzepatide 5 mg once weekly + lifestyle intervention
干预措施: Placebo (Drug)
Arm 1: Tirzepatide 5 mg once weekly + lifestyle intervention
干预措施: Reduced-calorie diet (Behavioral)
Arm 2: Tirzepatide 10 mg once weekly + lifestyle intervention
干预措施: Tirzepatide (Drug)
Arm 2: Tirzepatide 10 mg once weekly + lifestyle intervention
干预措施: Placebo (Drug)
Arm 2: Tirzepatide 10 mg once weekly + lifestyle intervention
干预措施: Reduced-calorie diet (Behavioral)
Arm 3: Tirzepatide 15 mg once weekly + lifestyle intervention
干预措施: Tirzepatide (Drug)
Arm 3: Tirzepatide 15 mg once weekly + lifestyle intervention
干预措施: Placebo (Drug)
Arm 3: Tirzepatide 15 mg once weekly + lifestyle intervention
干预措施: Reduced-calorie diet (Behavioral)
结局指标
主要结局
Mean percent change in body weight from randomization
时间窗: 72 Weeks
Percentage of participants achieving ≥5% body weight reduction from randomization
时间窗: 72 Weeks
次要结局
- Mean change in body weight(72 Weeks)
- Changes in cardiometabolic measures in triglycerides(72 weeks)