Aims/hypothesis

We conducted a systematic review and network meta-analysis to compare the efficacy and safety of s.c. administered tirzepatide vs s.c. administered semaglutide for adults of both sexes with type 2 diabetes mellitus.

Methods

We searched PubMed and Cochrane up to 11 November 2023 for RCTs with an intervention duration of at least 12 weeks assessing s.c. tirzepatide at maintenance doses of 5 mg, 10 mg or 15 mg once weekly, or s.c. semaglutide at maintenance doses of 0.5 mg, 1.0 mg or 2.0 mg once weekly, in adults with type 2 diabetes, regardless of background glucose-lowering treatment. Eligible trials compared any of the specified doses of tirzepatide and semaglutide against each other, placebo or other glucose-lowering drugs. Primary outcomes were changes in HbA_1c and body weight from baseline. Secondary outcomes were achievement of HbA_1c target of ≤48 mmol/mol (≤6.5%) or <53 mmol/mol (<7.0%), body weight loss of at least 10%, and safety outcomes including gastrointestinal adverse events and severe hypoglycaemia. We used version 2 of the Cochrane risk-of-bias tool (ROB 2) to assess the risk of bias, conducted frequentist random-effects network meta-analyses and evaluated confidence in effect estimates utilising the Confidence In Network Meta-Analysis (CINeMA) framework.

Results

A total of 28 trials with 23,622 participants (44.2% female) were included. Compared with placebo, tirzepatide 15 mg was the most efficacious treatment in reducing HbA_1c (mean difference −21.61 mmol/mol [−1.96%]) followed by tirzepatide 10 mg (−20.19 mmol/mol [−1.84%]), semaglutide 2.0 mg (−17.74 mmol/mol [−1.59%]), tirzepatide 5 mg (−17.60 mmol/mol [−1.60%]), semaglutide 1.0 mg (−15.25 mmol/mol [−1.39%]) and semaglutide 0.5 mg (−12.00 mmol/mol [−1.09%]). In between-drug comparisons, all tirzepatide doses were comparable with semaglutide 2.0 mg and superior to semaglutide 1.0 mg and 0.5 mg. Compared with placebo, tirzepatide was more efficacious than semaglutide for reducing body weight, with reductions ranging from 9.57 kg (tirzepatide 15 mg) to 5.27 kg (tirzepatide 5 mg). Semaglutide had a less pronounced effect, with reductions ranging from 4.97 kg (semaglutide 2.0 mg) to 2.52 kg (semaglutide 0.5 mg). In between-drug comparisons, tirzepatide 15 mg, 10 mg and 5 mg demonstrated greater efficacy than semaglutide 2.0 mg, 1.0 mg and 0.5 mg, respectively. Both drugs increased incidence of gastrointestinal adverse events compared with placebo, while neither tirzepatide nor semaglutide increased the risk of serious adverse events or severe hypoglycaemia.

Conclusions/interpretation

Our data show that s.c. tirzepatide had a more pronounced effect on HbA_1c and weight reduction compared with s.c. semaglutide in people with type 2 diabetes. Both drugs, particularly higher doses of tirzepatide, increased gastrointestinal adverse events.

Registration

PROSPERO registration no. CRD42022382594

Graphical Abstract

中文翻译：

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皮下注射替泽帕肽与索马鲁肽治疗成人 2 型糖尿病：随机对照试验的系统评价和网络荟萃分析

目标/假设

我们进行了系统评价和网络荟萃分析，以比较皮下注射替西帕肽与皮下注射索马鲁肽对患有 2 型糖尿病的成年男女的疗效和安全性。

方法

我们检索了截至 2023 年 11 月 11 日的 PubMed 和 Cochrane 中干预持续时间至少为 12 周的随机对照试验，评估每周一次 5 mg、10 mg 或 15 mg 维持剂量的 sc 替泽帕肽，或 0.5 mg、1.0 mg 维持剂量的 sc 索马鲁肽成人 2 型糖尿病患者每周服用 1 毫克或 2.0 毫克，无论背景降糖治疗如何。符合条件的试验将任何指定剂量的替西帕肽和索马鲁肽彼此、安慰剂或其他降糖药物进行比较。主要结果是 HbA _1c和体重相对于基线的变化。次要结局是实现 HbA1c _≤48 mmol/mol (≤6.5%) 或 <53 mmol/mol (<7.0%) 目标、体重减轻至少 10%，以及安全结局，包括胃肠道不良事件和严重低血糖。我们使用 Cochrane 偏倚风险工具 (ROB 2) 版本 2 来评估偏倚风险，进行频率随机效应网络荟萃分析，并利用网络荟萃分析置信度 (CINeMA) 评估效果估计的置信度框架。

结果

总共纳入了 28 项试验，共有 23,622 名参与者（44.2% 为女性）。与安慰剂相比，替泽帕肽 15 mg 是降低 HbA _1c最有效的治疗方法（平均差 -21.61 mmol/mol [-1.96%]），其次是替泽帕肽 10 mg（-20.19 mmol/mol [-1.84%]）、索马鲁肽 2.0 mg (-17.74 mmol/mol [-1.59%])、替西帕肽 5 mg (-17.60 mmol/mol [-1.60%])、索马鲁肽 1.0 mg (-15.25 mmol/mol [-1.39%]) 和索马鲁肽 0.5 mg ( −12.00 mmol/mol [−1.09%]）。在药物间比较中，所有替西帕肽剂量与索马鲁肽 2.0 mg 相当，优于索马鲁肽 1.0 mg 和 0.5 mg。与安慰剂相比，替泽帕肽比索马鲁肽更有效地减轻体重，减轻幅度为 9.57 公斤（替泽帕肽 15 毫克）至 5.27 公斤（替泽帕肽 5 毫克）。索马鲁肽的效果不太明显，减少范围为 4.97 kg（索马鲁肽 2.0 mg）至 2.52 kg（索马鲁肽 0.5 mg）。在药物间比较中，替西帕肽 15 mg、10 mg 和 5 mg 的疗效分别优于索马鲁肽 2.0 mg、1.0 mg 和 0.5 mg。与安慰剂相比，这两种药物都会增加胃肠道不良事件的发生率，而替西帕肽和索马鲁肽均不会增加严重不良事件或严重低血糖的风险。

结论/解释

我们的数据显示，与皮下注射索马鲁肽相比，皮下注射替泽帕肽对 2 型糖尿病患者的_HbA1c和体重减轻效果更显着。这两种药物，尤其是较高剂量的替泽帕肽，都会增加胃肠道不良事件。

登记

普洛斯彼罗注册号CRD42022382594

图形概要