JAMA: Tirzepatide vs.赖脯胰岛素联合基础胰岛素治疗2型糖尿病的比较：SURPASS-6随机临床试验

2023-10-07 来源：JAMA

本文由小咖机器人翻译整理

期刊来源：JAMA

文献发表时间：2023-10-03

原文链接：https://jamanetwork.com/journals/jama/article-abstract/2810386

关键点内容如下：

问题

在基础胰岛素控制不佳的2型糖尿病患者中，在甘精胰岛素治疗的基础上加用每周一次的tirzepatide与每日三次的赖脯胰岛素对血糖控制有何影响？

调查结果

在该随机临床试验（n=1428）中，在第52周时，糖化血红蛋白（HbA1c）的平均变化在使用tirzepatide时为-2.1%，而在使用赖脯胰岛素时为-1.1%；治疗差异具有统计学意义，较少的低血糖和更多的体重减轻。

意义

在基础胰岛素治疗且血糖控制不佳的2型糖尿病患者中，在甘精胰岛素基础上加用每周一次的Tirzepatide与餐时赖脯胰岛素相比，HbA1c下降幅度更大，体重减轻更多，低血糖更少。

摘要内容如下：

重要性

Tirzepatide是一种葡萄糖依赖性促胰岛素多肽和胰高血糖素样肽-1受体激动剂，用于治疗2型糖尿病。与餐时胰岛素相比，基础胰岛素治疗血糖控制不佳的患者加用Tirzepatide的疗效和安全性尚未得到描述。

目的

评估提拉他肽与赖脯胰岛素作为胰岛素Glargine辅助治疗的有效性和安全性。

研究设计和参与者

这项开放标签的3B期临床试验在15个国家的135个地点进行（参与者于2020年10月19日至2022年11月1日登记），1428名成人2型糖尿病患者服用基础胰岛素。

干预措施

受试者随机（按1:1:1:3的比例）接受每周一次皮下注射Tirzepatide（5 mg[n=243]、10 mg[n=238]或15 mg[n=236]）或每日三次餐用赖脯胰岛素（n=708）。

主要结局和措施

结果包括第52周时，在HbA1c相对于基线的变化方面，除甘精胰岛素外，Tirzepatide（合并队列）与赖脯胰岛素的非劣效性（非劣效性界值，0.3%）。关键的次要终点包括体重变化和达到低于7.0%的血红蛋白A1c（HbA1c）目标的参与者百分比。

结果

在1428名随机参与者中，（824名[57.7%]女性；平均[SD]年龄，58.8[9.7]岁；平均[SD]糖化血红蛋白，8.8%[1.0%]），1304（91.3%的）完成了试验。在第52周，使用Tirzepatide（合并队列）的HbA1c相对于基线的估计平均变化为-2.1%vs赖脯胰岛素的-1.1%，导致平均HbA1c水平为6.7%vs 7.7%（估计治疗差异，-0.98%[95%CI，-1.17%至-0.79%]；P<.001）；结果符合非劣效性标准，并达到统计学优势。体重相对于基线的估计平均变化在使用tirzepatide时为-9.0 kg，在使用赖脯胰岛素时为3.2 kg（估计治疗差异，-12.2 kg[95%CI，-13.4至-10.9]）。糖化血红蛋白（HbA1c）低于7.0%的受试者中，68%（716人中的483人）使用了羟苄噻嗪，36%（708人中的256人）使用了赖脯胰岛素（比值比，4.2[95%CI，3.2-5.5]）。最常见的不良事件是轻度至中度胃肠道症状，（恶心:14%-26%；腹泻:11%-15%；呕吐:5%-13%）。低血糖事件率（血糖水平<54 mg/DL或严重低血糖），使用tirzepatide（合并）的患者每年发生0.4起事件，使用赖脯胰岛素的患者每年发生4.4起事件。

结论和相关性

在使用基础胰岛素治疗血糖控制不佳的2型糖尿病患者中，与餐时胰岛素和甘精胰岛素相比，每周一次的tirzepatide作为甘精胰岛素的额外治疗可降低糖化血红蛋白（HbA1c）和体重，并减少低血糖。

英文原文如下：

Key Points

Question What is the effect on glycemic control of adding once-weekly tirzepatide vs thrice-daily prandial insulin lispro to insulin glargine treatment in inadequately controlled basal insulin–treated type 2 diabetes?

Findings In this randomized clinical trial (N = 1428), mean change in hemoglobin A1c (HbA1c) at week 52 was −2.1% with tirzepatide vs −1.1% with insulin lispro; treatment differences were statistically significant with less hypoglycemia and more body weight reduction with tirzepatide.

Meaning Adding once-weekly tirzepatide vs prandial insulin lispro to insulin glargine in basal insulin-treated patients with type 2 diabetes and inadequate glycemic control resulted in greater reductions in HbA1c along with more weight loss and less hypoglycemia.

Abstract

Importance Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes. Efficacy and safety of adding tirzepatide vs prandial insulin to treatment in patients with inadequate glycemic control with basal insulin have not been described.

Objective To assess the efficacy and safety of tirzepatide vs insulin lispro as an adjunctive therapy to insulin glargine.

Design, Setting, and Participants This open-label, phase 3b clinical trial was conducted at 135 sites in 15 countries (participants enrolled from October 19, 2020, to November 1, 2022) in 1428 adults with type 2 diabetes taking basal insulin.

Interventions Participants were randomized (in a 1:1:1:3 ratio) to receive once-weekly subcutaneous injections of tirzepatide (5 mg [n = 243], 10 mg [n = 238], or 15 mg [n = 236]) or prandial thrice-daily insulin lispro (n = 708).

Main Outcomes and Measures Outcomes included noninferiority of tirzepatide (pooled cohort) vs insulin lispro, both in addition to insulin glargine, in HbA1c change from baseline at week 52 (noninferiority margin, 0.3%). Key secondary end points included change in body weight and percentage of participants achieving hemoglobin A1c (HbA1c) target of less than 7.0%.

Results Among 1428 randomized participants (824 [57.7%] women; mean [SD] age, 58.8 [9.7] years; mean [SD] HbA1c, 8.8% [1.0%]), 1304 (91.3%) completed the trial. At week 52, estimated mean change from baseline in HbA1c with tirzepatide (pooled cohort) was −2.1% vs −1.1% with insulin lispro, resulting in mean HbA1c levels of 6.7% vs 7.7% (estimated treatment difference, −0.98% [95% CI, −1.17% to −0.79%]; P < .001); results met noninferiority criteria and statistical superiority was achieved. Estimated mean change from baseline in body weight was −9.0 kg with tirzepatide and 3.2 kg with insulin lispro (estimated treatment difference, −12.2 kg [95% CI, −13.4 to −10.9]). The percentage of participants reaching HbA1c less than 7.0% was 68% (483 of 716) with tirzepatide and 36% (256 of 708) with insulin lispro (odds ratio, 4.2 [95% CI, 3.2-5.5]). The most common adverse events with tirzepatide were mild to moderate gastrointestinal symptoms (nausea: 14%-26%; diarrhea: 11%-15%; vomiting: 5%-13%). Hypoglycemia event rates (blood glucose level <54 mg/dL or severe hypoglycemia) were 0.4 events per patient-year with tirzepatide (pooled) and 4.4 events per patient-year with insulin lispro.

Conclusions and Relevance In people with inadequately controlled type 2 diabetes treated with basal insulin, weekly tirzepatide compared with prandial insulin as an additional treatment with insulin glargine demonstrated reductions in HbA1c and body weight with less hypoglycemia.

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