5-Year simulation of diabetes-related complications in people treated with tirzepatide or semaglutide versus insulin glargine.
5-Year simulation of diabetes-related complications in people treated with tirzepatide or semaglutide versus insulin glargine.
复制标题
对接受替泽帕肽或索马鲁肽与甘精胰岛素治疗的患者进行糖尿病相关并发症的 5 年模拟。
DOI：
10.1111/dom.15332
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Shao,Hui
中科院分区：
文献类型：
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作者：
Niu,Shu;Alkhuzam,KhalidA;Guan,Dawei;Jiao,Tianze;Shi,Lizheng;Fonseca,Vivian;Laiteerapong,Neda;Ali,MohammedK;Schatz,DesmondA;Guo,Jingchuan;Shao,Hui
目的本研究采用建立、关联、评估和验证结果（BRAVO）糖尿病模拟模型，比较了替瑞帕肽、Semaglutide和甘精胰岛素治疗2型糖尿病患者5年大血管和微血管并发症的发生率。研究设计和方法本研究是一项为期5年的SURPASS-2外推试验，增加了甘精胰岛素组作为额外的对照。从SUSTAIN-4和SURPASS-2试验中获得了替瑞帕肽（5、10或15 mg）、Semaglutide（1 mg）和甘精胰岛素对糖化血红蛋白、收缩压、低密度脂蛋白和体重的1年治疗效应。我们使用BRAVO模型预测两种情况下每个研究组的5年并发症：1年治疗效果持续存在（乐观）或在5年内减少到无结果与甘精胰岛素相比，我们预测心血管不良事件的5年风险降低[率比（RR）0.64，95%置信区间（CI）0.61 - 0.67]和微血管复合终点（RR 0.67，95% CI 0.64 - 0.70），心血管不良事件的5年风险降低（RR 0.75，95% CI 0.72 - 0.79）和微血管复合终点（RR 0.79，95% CI 0.76 - 0.82）。较低剂量的替西帕肽也有类似的益处，尽管较小。在保守情况下，替瑞帕肽和Semaglutide的治疗效应较小，但仍显著高于甘精胰岛素。与甘精胰岛素相比，在乐观情况下，15 mg替瑞帕肽的糖尿病相关并发症事件和死亡率的5年风险降低范围为49%-10%，在保守情况下，降低17%-33%。在2型糖尿病患者中，替瑞帕肽和Semaglutide显示出降低大血管和微血管并发症风险的潜力，与甘精胰岛素相比，基于当前建模假设，替瑞帕肽（15 mg）可能优于Semaglutide（1 mg）。虽然BRAVO模型提供了一些见解，但应在前瞻性临床试验中进一步验证替瑞帕肽的长期心血管获益。
AimThis study compared the 5‐year incidence rate of macrovascular and microvascular complications for tirzepatide, semaglutide and insulin glargine in individuals with type 2 diabetes, using the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes simulation model.Research Design and MethodsThis study was a 5‐year SURPASS‐2 trial extrapolation, with an insulin glargine arm added as an additional comparator. The 1‐year treatment effects of tirzepatide (5, 10 or 15 mg), semaglutide (1 mg) and insulin glargine on glycated haemoglobin, systolic blood pressure, low‐density lipoprotein and body weights were obtained from the SUSTAIN‐4 and SURPASS‐2 trials. We used the BRAVO model to predict 5‐year complications for each study arm under two scenarios: the 1‐year treatment effects persisted (optimistic) or diminished to none in 5 years (conservative).ResultsWhen compared with insulin glargine, we projected a 5‐year risk reduction in cardiovascular adverse events [rate ratio (RR) 0.64, 95% confidence interval (CI) 0.61‐0.67] and microvascular composite (RR 0.67, 95% CI 0.64‐0.70) with 15 mg tirzepatide, and 5‐year risk reduction in cardiovascular adverse events (RR 0.75, 95% CI 0.72‐0.79) and microvascular composite (RR 0.79, 95% CI 0.76‐0.82) with semaglutide (1 mg) under an optimistic scenario. Lower doses of tirzepatide also had similar, albeit smaller benefits. Treatment effects for tirzepatide and semaglutide were smaller but still significantly higher than insulin glargine under a conservative scenario. The 5‐year risk reduction in diabetes‐related complication events and mortality for the 15 mg tirzepatide compared with insulin glargine ranged from 49% to 10% under an optimistic scenario, which was reduced by 17%‐33% when a conservative scenario was assumed.ConclusionWith the use of the BRAVO diabetes model, tirzepatide and semaglutide exhibited potential to reduce the risk of macrovascular and microvascular complications among individuals with type 2 diabetes, compared with insulin glargine in a 5‐year window. Based on the current modelling assumptions, tirzepatide (15 mg) may potentially outperform semaglutide (1 mg). While the BRAVO model offered insights, the long‐term cardiovascular benefit of tirzepatide should be further validated in a prospective clinical trial.