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Abstract：
OBJECTIVE: 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 HbA1c and body weight from baseline. Secondary outcomes were achievement of HbA1c 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 HbA1c (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: Our data show that s.c. tirzepatide had a more pronounced effect on HbA1c 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.
BACKGROUND: PROSPERO registration no. CRD42022382594.
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 HbA1c and body weight from baseline. Secondary outcomes were achievement of HbA1c 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 HbA1c (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: Our data show that s.c. tirzepatide had a more pronounced effect on HbA1c 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.
BACKGROUND: PROSPERO registration no. CRD42022382594.
摘要：
目的：我们进行了系统评价和网络荟萃分析，以比较替吉普肽与替吉普肽对2型糖尿病男女成人的疗效和安全性。
方法：我们搜索了截至2023年11月11日的PubMed和Cochrane的随机对照试验，其干预持续时间至少为12周，以5mg的维持剂量评估s.c.10毫克或15毫克，每周一次，或s.c.semaglutide，维持剂量为0.5mg，1.0毫克或2.0毫克，每周一次，在患有2型糖尿病的成年人中，无论背景降糖治疗。符合条件的试验比较了任何指定剂量的替拉西帕肽和司马鲁肽，安慰剂或其他降糖药物。主要结果是HbA1c和体重相对于基线的变化。次要结果是实现HbA1c目标≤48mmol/mol（≤6.5％）或<53mmol/mol（<7.0％），体重减轻至少10%，和安全性结局，包括胃肠道不良事件和严重低血糖。我们使用Cochrane偏差风险工具(ROB2)的版本2来评估偏差风险，进行了频繁随机效应网络荟萃分析，并利用网络荟萃分析信心（CINeMA）框架评估了效应估计的信心。
结果：共纳入28项试验，23,622名参与者（44.2%为女性）。与安慰剂相比，在降低HbA1c（平均差-21.61mmol/mol[-1.96%]）方面，替利平肽15mg是最有效的治疗方法，其次是替利平肽10mg（-20.19mmol/mol[-1.84%]），塞马鲁肽2.0mg（-17.74mmol/mol[-1.59%]），替拉肽5mg(-17.60mmol/mol[-1.60%]),司马鲁肽1.0mg（-15.25mmol/mol[-1.39%]）和司马鲁肽0.5mg（-12.00mmol/mol[-1.09%]）。在药物之间的比较中，所有替拉西帕肽剂量与司马鲁肽2.0mg相当,优于司马鲁肽1.0mg和0.5mg.与安慰剂相比，在减轻体重方面，替瑞哌肽比塞马鲁肽更有效，减少范围从9.57kg（替利平肽15mg）到5.27kg（替利平肽5mg）。塞马鲁肽的效果不太明显，减少范围从4.97公斤（司马鲁肽2.0毫克）到2.52公斤（司马鲁肽0.5毫克）。在药物之间的比较中，替瑞哌肽15毫克，10毫克和5毫克显示出比司马鲁肽2.0毫克更大的疗效，1.0毫克和0.5毫克，分别。与安慰剂相比，两种药物都增加了胃肠道不良事件的发生率，而替瑞沙肽和司美鲁肽均不增加严重不良事件或严重低血糖的风险。
结论：我们的数据表明，在2型糖尿病患者中，与sc.semaglutide相比，sc.tirzepatide对HbA1c和体重减轻的影响更明显。两种药物,特别是较高剂量的替瑞哌肽，胃肠道不良事件增加。
背景：PROSPERO注册号。CRD42022382594。
方法：我们搜索了截至2023年11月11日的PubMed和Cochrane的随机对照试验，其干预持续时间至少为12周，以5mg的维持剂量评估s.c.10毫克或15毫克，每周一次，或s.c.semaglutide，维持剂量为0.5mg，1.0毫克或2.0毫克，每周一次，在患有2型糖尿病的成年人中，无论背景降糖治疗。符合条件的试验比较了任何指定剂量的替拉西帕肽和司马鲁肽，安慰剂或其他降糖药物。主要结果是HbA1c和体重相对于基线的变化。次要结果是实现HbA1c目标≤48mmol/mol（≤6.5％）或<53mmol/mol（<7.0％），体重减轻至少10%，和安全性结局，包括胃肠道不良事件和严重低血糖。我们使用Cochrane偏差风险工具(ROB2)的版本2来评估偏差风险，进行了频繁随机效应网络荟萃分析，并利用网络荟萃分析信心（CINeMA）框架评估了效应估计的信心。
结果：共纳入28项试验，23,622名参与者（44.2%为女性）。与安慰剂相比，在降低HbA1c（平均差-21.61mmol/mol[-1.96%]）方面，替利平肽15mg是最有效的治疗方法，其次是替利平肽10mg（-20.19mmol/mol[-1.84%]），塞马鲁肽2.0mg（-17.74mmol/mol[-1.59%]），替拉肽5mg(-17.60mmol/mol[-1.60%]),司马鲁肽1.0mg（-15.25mmol/mol[-1.39%]）和司马鲁肽0.5mg（-12.00mmol/mol[-1.09%]）。在药物之间的比较中，所有替拉西帕肽剂量与司马鲁肽2.0mg相当,优于司马鲁肽1.0mg和0.5mg.与安慰剂相比，在减轻体重方面，替瑞哌肽比塞马鲁肽更有效，减少范围从9.57kg（替利平肽15mg）到5.27kg（替利平肽5mg）。塞马鲁肽的效果不太明显，减少范围从4.97公斤（司马鲁肽2.0毫克）到2.52公斤（司马鲁肽0.5毫克）。在药物之间的比较中，替瑞哌肽15毫克，10毫克和5毫克显示出比司马鲁肽2.0毫克更大的疗效，1.0毫克和0.5毫克，分别。与安慰剂相比，两种药物都增加了胃肠道不良事件的发生率，而替瑞沙肽和司美鲁肽均不增加严重不良事件或严重低血糖的风险。
结论：我们的数据表明，在2型糖尿病患者中，与sc.semaglutide相比，sc.tirzepatide对HbA1c和体重减轻的影响更明显。两种药物,特别是较高剂量的替瑞哌肽，胃肠道不良事件增加。
背景：PROSPERO注册号。CRD42022382594。
