BACKGROUND Obesity is chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes. METHODS We performed a phase 3, double-blind, randomized, controlled trial in which 2539 participants with obesity, of whom 1032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo. The current analysis involved the participants with both obesity and prediabetes, who received their assigned dose of tirzepatide or placebo for a total of 176 weeks, followed by a 17-week off-treatment period. The three key secondary end points, which were controlled for type I error, were the percent change in body weight from baseline to week 176 and onset of type 2 diabetes during the 176-week and 193-week periods. RESULTS At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was -12.3% with the 5-mg dose, -18.7% with the 10-mg dose, and -19.7% with the 15-mg dose, as compared with -1.3% among those who received placebo (P<0.001 for all comparisons with placebo). Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0 to 0.1; P<0.001). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12; 95% CI, 0.1 to 0.2; P<0.001). Other than coronavirus disease 2019, the most common adverse events were gastrointestinal, most of which were mild to moderate in severity and occurred primarily during the dose-escalation period in the first 20 weeks of the trial. No new safety signals were identified. CONCLUSIONS Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo. (Funded by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

中文翻译：

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Tirzepatide 用于肥胖治疗和糖尿病预防。


背景 肥胖是慢性疾病，是包括 2 型糖尿病在内的无数其他疾病的因果前兆。在对 SURMOUNT-1 试验的早期分析中，tirzepatide 被证明可在 72 周内显着和持续地减轻肥胖患者的体重。在这里，我们报告了 tirzepatide 的 3 年安全性结果及其在肥胖和糖尿病前期患者中减轻体重和延缓进展为 2 型糖尿病的疗效。方法 我们进行了一项 3 期、双盲、随机、对照试验，其中 2539 名肥胖参与者，其中 1032 名还患有糖尿病前期，以 1：1：1：1 的比例分配接受每周一次剂量为 5 mg、10 mg 或 15 mg 的 tirzepatide 或安慰剂。目前的分析涉及肥胖和糖尿病前期的参与者，他们接受了指定剂量的 tirzepatide 或安慰剂，总共 176 周，然后是 17 周的停药期。控制 I 型错误的三个关键次要终点是体重从基线到第 176 周的百分比变化以及 176 周和 193 周期间 2 型糖尿病的发作。结果 在 176 周时，接受 tirzepatide 的参与者体重的平均百分比变化为 5 毫克剂量的 -12.3%，10 毫克剂量的 -18.7%，15 毫克剂量的 -19.7%，而接受安慰剂的参与者为 -1.3%（与安慰剂的所有比较的 P<0.001）。与安慰剂组相比，tirzepatide 组被诊断为 2 型糖尿病的参与者更少（1.3% vs. 13.3%;风险比，0.07;95% 置信区间 [CI]，0.0 至 0.1;P<0.001）。在停止治疗或安慰剂 17 周后，接受 tirzepatide 的参与者中有 2.4% 和 13.接受安慰剂的患者中有 7% 患有 2 型糖尿病（风险比，0.12;95% CI，0.1 至 0.2;P<0.001）。除 2019 冠状病毒病外，最常见的不良事件是胃肠道不良事件，其中大多数为轻度至中度严重程度，主要发生在试验前 20 周的剂量递增期间。未发现新的安全信号。结论 与安慰剂相比，肥胖和糖尿病前期患者接受 tirzepatide 治疗 3 年后体重显著持续减轻，进展为 2 型糖尿病的风险显著降低。（由 Eli Lilly 资助;SURMOUNT-1 ClinicalTrials.gov 编号，NCT04184622.）。