Abstract：
OBJECTIVE: To assess the efficacy and safety of tirzepatide versus insulin glargine in people with type 2 diabetes (T2D) by baseline body mass index (BMI).
METHODS: Participants with T2D from the Phase 3 SURPASS-AP-Combo trial (NCT04093752) were categorized into three BMI subgroups (normal weight [<25 kg/m2 ], overweight [≥25 and <30 kg/m2 ], and obese [≥30 kg/m2 ]) according to World Health Organization criteria. Exploratory outcomes including glycaemic control, body weight, cardiometabolic risk, and safety were compared among three tirzepatide doses (5, 10 or 15 mg) and insulin glargine.
RESULTS: Of 907 participants, 235 (25.9%) had a BMI <25 kg/m2 , 458 (50.5%) a BMI ≥25 to <30 kg/m2 , and 214 (23.6%) a BMI ≥30 kg/m2 at baseline. At Week 40, all tirzepatide doses led to a greater reduction in mean glycated haemoglobin (HbA1c; -2.0% to -2.8% vs. -0.8% to -1.0%, respectively) and percent change in body weight (-5.5% to -10.8% vs. 1.0% to 2.5%, respectively) versus insulin glargine, across the BMI subgroups. Compared with insulin glargine, a higher proportion of tirzepatide-treated participants achieved treatment goals for HbA1c and body weight reduction. Improvements in other cardiometabolic indicators were also observed with tirzepatide across all the BMI subgroups. The safety profile of tirzepatide was similar across all subgroups by BMI. The most frequent adverse events with tirzepatide were gastrointestinal-related events and decreased appetite, with relatively few events leading to treatment discontinuation.
CONCLUSIONS: In participants with T2D, regardless of baseline BMI, treatment with tirzepatide resulted in statistically significant and clinically meaningful glycaemic reductions and body weight reductions compared with insulin glargine, with a safety profile consistent with previous reports.
METHODS: Participants with T2D from the Phase 3 SURPASS-AP-Combo trial (NCT04093752) were categorized into three BMI subgroups (normal weight [<25 kg/m2 ], overweight [≥25 and <30 kg/m2 ], and obese [≥30 kg/m2 ]) according to World Health Organization criteria. Exploratory outcomes including glycaemic control, body weight, cardiometabolic risk, and safety were compared among three tirzepatide doses (5, 10 or 15 mg) and insulin glargine.
RESULTS: Of 907 participants, 235 (25.9%) had a BMI <25 kg/m2 , 458 (50.5%) a BMI ≥25 to <30 kg/m2 , and 214 (23.6%) a BMI ≥30 kg/m2 at baseline. At Week 40, all tirzepatide doses led to a greater reduction in mean glycated haemoglobin (HbA1c; -2.0% to -2.8% vs. -0.8% to -1.0%, respectively) and percent change in body weight (-5.5% to -10.8% vs. 1.0% to 2.5%, respectively) versus insulin glargine, across the BMI subgroups. Compared with insulin glargine, a higher proportion of tirzepatide-treated participants achieved treatment goals for HbA1c and body weight reduction. Improvements in other cardiometabolic indicators were also observed with tirzepatide across all the BMI subgroups. The safety profile of tirzepatide was similar across all subgroups by BMI. The most frequent adverse events with tirzepatide were gastrointestinal-related events and decreased appetite, with relatively few events leading to treatment discontinuation.
CONCLUSIONS: In participants with T2D, regardless of baseline BMI, treatment with tirzepatide resulted in statistically significant and clinically meaningful glycaemic reductions and body weight reductions compared with insulin glargine, with a safety profile consistent with previous reports.
摘要：
目的：通过基线体重指数（BMI）评估2型糖尿病（T2D）患者使用替利西帕肽与甘精胰岛素的疗效和安全性。
方法：来自SURPASS-AP-Combo3期试验（NCT04093752）的T2D参与者分为三个BMI亚组（正常体重[<25kg/m2]，超重[≥25且<30kg/m2]，和肥胖[≥30kg/m2])根据世界卫生组织的标准。探索性结果，包括血糖控制，体重,心脏代谢风险，比较了三种剂量(5,10或15mg)的替利西帕肽和甘精胰岛素的安全性.
结果：在907名参与者中，235（25.9％）的BMI<25kg/m2，458（50.5%）BMI≥25至<30kg/m2，基线时BMI≥30kg/m2214（23.6%）。在第40周时，所有替瑞哌肽剂量均导致平均糖化血红蛋白降低更大（HbA1c;-2.0％至-2.8％vs.-0.8%至-1.0%，分别)和体重变化百分比(-5.5%至-10.8%vs.1.0%至2.5%，分别)与甘精胰岛素相比，在BMI亚组。与甘精胰岛素相比，较高比例的替利西帕肽治疗的参与者实现了HbA1c和体重减轻的治疗目标.在所有BMI亚组中，使用替拉肽也观察到其他心脏代谢指标的改善。通过BMI，所有亚组的替利西帕肽的安全性相似。替瑞哌肽最常见的不良事件是胃肠道相关事件和食欲下降，导致治疗中断的事件相对较少。
结论：在T2D患者中，无论基线BMI如何，与甘精胰岛素相比，使用替瑞哌肽治疗可导致统计学上显著且有临床意义的血糖下降和体重下降，安全性与以前的报告一致。
方法：来自SURPASS-AP-Combo3期试验（NCT04093752）的T2D参与者分为三个BMI亚组（正常体重[<25kg/m2]，超重[≥25且<30kg/m2]，和肥胖[≥30kg/m2])根据世界卫生组织的标准。探索性结果，包括血糖控制，体重,心脏代谢风险，比较了三种剂量(5,10或15mg)的替利西帕肽和甘精胰岛素的安全性.
结果：在907名参与者中，235（25.9％）的BMI<25kg/m2，458（50.5%）BMI≥25至<30kg/m2，基线时BMI≥30kg/m2214（23.6%）。在第40周时，所有替瑞哌肽剂量均导致平均糖化血红蛋白降低更大（HbA1c;-2.0％至-2.8％vs.-0.8%至-1.0%，分别)和体重变化百分比(-5.5%至-10.8%vs.1.0%至2.5%，分别)与甘精胰岛素相比，在BMI亚组。与甘精胰岛素相比，较高比例的替利西帕肽治疗的参与者实现了HbA1c和体重减轻的治疗目标.在所有BMI亚组中，使用替拉肽也观察到其他心脏代谢指标的改善。通过BMI，所有亚组的替利西帕肽的安全性相似。替瑞哌肽最常见的不良事件是胃肠道相关事件和食欲下降，导致治疗中断的事件相对较少。
结论：在T2D患者中，无论基线BMI如何，与甘精胰岛素相比，使用替瑞哌肽治疗可导致统计学上显著且有临床意义的血糖下降和体重下降，安全性与以前的报告一致。
