Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Center for Drug Evaluation and Safety, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Diabetes Obes Metab. 2024 Feb;26(2):463-472. doi: 10.1111/dom.15332. Epub 2023 Oct 22.
This 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.
This 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).
When 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.
With 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.
本研究使用 Building、Relating、Assessing、and Validating Outcomes（BRAVO）糖尿病模拟模型，比较了替尔泊肽、司美格鲁肽和甘精胰岛素在 2 型糖尿病患者中的 5 年大血管和微血管并发症发生率。
这是一项 SURPASS-2 试验的 5 年外推研究，增加了甘精胰岛素组作为额外的对照。替尔泊肽（5、10 或 15mg）、司美格鲁肽（1mg）和甘精胰岛素在 1 年内对糖化血红蛋白、收缩压、低密度脂蛋白和体重的治疗效果来自 SUSTAIN-4 和 SURPASS-2 试验。我们使用 BRAVO 模型在两种情况下预测每个研究臂的 5 年并发症：1 年的治疗效果持续（乐观）或在 5 年内降至零（保守）。
与甘精胰岛素相比，我们预测 15mg 替尔泊肽可降低 5 年心血管不良事件风险（风险比 [RR] 0.64，95%置信区间 [CI] 0.61-0.67）和微血管复合事件风险（RR 0.67，95% CI 0.64-0.70），而司美格鲁肽（1mg）可降低 5 年心血管不良事件风险（RR 0.75，95% CI 0.72-0.79）和微血管复合事件风险（RR 0.79，95% CI 0.76-0.82）在乐观情况下。替尔泊肽的较低剂量也具有类似但略小的益处。在保守情况下，替尔泊肽和司美格鲁肽的治疗效果较小，但仍明显高于甘精胰岛素。与甘精胰岛素相比，15mg 替尔泊肽在乐观情况下降低了 2 型糖尿病患者的糖尿病相关并发症事件和死亡率风险，范围从 49%到 10%，而在保守情况下降低了 17%-33%。
使用 BRAVO 糖尿病模型，与甘精胰岛素相比，替尔泊肽和司美格鲁肽在 5 年的时间内具有降低 2 型糖尿病患者大血管和微血管并发症风险的潜力。基于当前的建模假设，替尔泊肽（15mg）可能优于司美格鲁肽（1mg）。虽然 BRAVO 模型提供了一些见解，但替尔泊肽的长期心血管获益仍需在前瞻性临床试验中进一步验证。
