Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.

We aimed to assess the efficacy and safety of retatrutide as a monotherapy in people with type 2 diabetes that is inadequately controlled by diet and exercise alone.

我们的目标是评估Retatrutide作为单一疗法在仅通过饮食和运动无法充分控制的2型糖尿病患者中的疗效和安全性。

Methods

In this 40-week, phase 3, randomised, double-blind, placebo-controlledtrial at 48 sites in the USA, Mexico, and India, we recruited adults (aged ≥18 years) with type 2 diabetes that is inadequately controlled by diet and exercise alone, glycated haemoglobin (HbA1c) between 7·0% and 9·5% (53-80 mmol/mol), and BMI of at least 23 kg/m2.

在这项为期40周、在美国、墨西哥和印度的48个地点进行的3期、随机、双盲、安慰剂对照试验中，我们招募了18岁及以上的成年人，这些成年人患有仅通过饮食和运动无法控制的2型糖尿病，糖化血红蛋白（HbA1c）在7.0%至9.5%（53-80毫摩/升）之间，BMI至少为23 kg/m2。

Participants were randomly assigned (1:1:1:1) to receive retatrutide (4 mg, 9 mg, or 12 mg) or placebo by once-weekly subcutaneous injection.

参与者被随机分配（1:1:1:1）接受每周一次皮下注射的retatrutide（4毫克、9毫克或12毫克）或安慰剂。

The primary endpoint was the change in HbA1c concentration from baseline to week 40.

主要终点是基线至第40周HbA1c浓度的变化。

A key secondary endpoint was the percentage change in bodyweight from baseline to week 40.

一个关键的次要终点是基线至第40周体重百分比的变化。

This trial is registered with ClinicalTrials.gov, NCT06354660, and is completed.

该试验已在ClinicalTrials.gov注册，注册号为NCT06354660，并已完成。

Results

Between April 10, 2024, and April 21, 2025, 930 participants were screened and 537 (296 [55%] female and 241 [45%] male) were randomly assigned: 134 to retatrutide 4 mg, 133 to retatrutide 9 mg, 136 to retatrutide 12 mg, and 134 to placebo.

在2024年4月10日至2025年4月21日期间，共有930名参与者接受了筛选，其中537名（女性296名[55%]，男性241名[45%]）被随机分配：134名接受4毫克retatrutide治疗，133名接受9毫克retatrutide治疗，136名接受12毫克retatrutide治疗，另外134名接受安慰剂。

Baseline mean age was 48·8 years (SD 12·1), mean HbA1c concentration was 7·9% (SD 1·1), mean duration of diabetes was 2·5 years (SD 4·4), and mean BMI was 35·8 kg/m2 (SD 7·0). 490 (91%) participants completed the treatment period on study drug and 504 (94%) completed the study.

基线平均年龄为48.8岁（标准差12.1），平均糖化血红蛋白（HbA1c）浓度为7.9%（标准差1.1），糖尿病平均病程为2.5年（标准差4.4），平均体重指数（BMI）为35.8 kg/m²（标准差7.0）。490名（91%）参与者完成了研究药物的治疗期，504名（94%）完成了研究。

For the treatment regimen estimand, the mean change from baseline in HbA1c concentration was -1·69% (SE 0·11) with retatrutide 4 mg, -1·86% (0·10) with 9 mg, and -1·94% (0·08) with 12 mg, versus -0·81% (0·12) with placebo, resulting in estimated treatment differences versus placebo of -0·88% (95% CI -1·18 to -0·59) with retatrutide 4 mg, -1·04% (-1·32 to -0·76) with 9 mg, and -1·12% (-1·39 to -0·85) with 12 mg (all p<0·0001).

对于治疗方案的估计值，使用4毫克retatrutide的平均基线糖化血红蛋白（HbA1c）浓度变化为-1.69%（标准误0.11），使用9毫克的为-1.86%（0.10），使用12毫克的为-1.94%（0.08），而使用安慰剂的为-0.81%（0.12），与安慰剂相比，估计的治疗差异分别为-0.88%（95%置信区间-1.18至-0.59）使用4毫克retatrutide，-1.04%（-1.32至-0.76）使用9毫克，以及-1.12%（-1.39至-0.85）使用12毫克（所有p<0.0001）。

The mean percentage change from baseline in bodyweight was -11·5% (SE 0·7) with retatrutide 4 mg, -13·9% (0·8) with 9 mg, and -15·3% (0·8) with 12 mg, versus -2·6% (0·5) with placebo.

与基线相比，使用4毫克、9毫克和12毫克retatrutide的体重平均百分比变化分别为-11.5%（标准误0.7）、-13.9%（0.8）和-15.3%（0.8），而安慰剂组为-2.6%（0.5）。

The most frequent adverse events with retatrutide were generally mild to moderate gastrointestinal events, which subsided over time.

使用retatrutide最常见的不良事件通常是轻度至中度的胃肠道事件，随着时间的推移这些症状会逐渐减轻。

Study intervention discontinuations due to adverse events were 2-5% with retatrutide and 0% with placebo.

由于不良事件导致的研究干预中止率在使用retatrutide的患者中为2-5%，而在使用安慰剂的患者中为0%。

No severe hypoglycaemia was reported.

未报告严重低血糖事件。

Two deaths occurred during the study, both in the retatrutide 4 mg group and unrelated to the study drug.

研究期间发生了两例死亡，均发生在4毫克瑞他鲁肽组，且与研究药物无关。

interpretation

Retatrutide showed significant improvements in glycaemic control and bodyweight reduction as a monotherapy in adults with type 2 diabetes that is inadequately controlled with diet and exercise alone, with an adverse eventprofile consistent with molecules with GLP-1 agonist activity, supporting its potential as an effective treatment for type 2 diabetes.

瑞他鲁肽作为单药治疗，在饮食和运动控制不佳的2型糖尿病成人患者中显示出显著的血糖控制改善和体重减轻效果，其不良事件特征与具有GLP-1激动剂活性的分子一致，支持其作为2型糖尿病有效治疗的潜力。

funding

Eli Lilly and Company.

礼来公司