Institute for Healthcare Delivery Science, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY.
Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA.
Diabetes Care. 2023 Jun 1;46(6):1300-1310. doi: 10.2337/dc22-0772.
Eligibility for glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) has been expanded to patients with diabetes at lower cardiovascular risk, but whether treatment benefits differ by risk levels is not clear.
To investigate whether patients with varying risks differ in cardiovascular and renal benefits from GLP-1RA and SGLT2i with use of meta-analysis and meta-regression.
We performed a systematic review using PubMed through 7 November 2022.
We included reports of GLP-1RA and SGLT2i confirmatory randomized trials in adult patients with safety or efficacy end point data.
Hazard ratio (HR) and event rate data were extracted for mortality, cardiovascular, and renal outcomes.
We analyzed 9 GLP-1RA and 13 SGLT2i trials comprising 154,649 patients. Summary HRs were significant for cardiovascular mortality (GLP-1RA 0.87 and SGLT2i 0.86), major adverse cardiovascular events (0.87 and 0.88), heart failure (0.89 and 0.70), and renal (0.84 and 0.65) outcomes. For stroke, efficacy was significant for GLP-1RA (0.84) but not for SGLT2i (0.92). Associations between control arm cardiovascular mortality rates and HRs were nonsignificant. Five-year absolute risk reductions (0.80-4.25%) increased to 11.6% for heart failure in SGLT2i trials in patients with high risk (Pslope < 0.001). For GLP1-RAs, associations were nonsignificant.
Analyses were limited by lack of patient-level data, consistency in end point definitions, and variation in cardiovascular mortality rates for GLP-1RA trials.
Relative effects of novel diabetes drugs are preserved across baseline cardiovascular risk, whereas absolute benefits increase at higher risks, particularly regarding heart failure. Our findings suggest a need for baseline risk assessment tools to identify variation in absolute treatment benefits and improve decision-making.
GLP-1 受体激动剂（GLP-1RA）和钠-葡萄糖协同转运蛋白 2 抑制剂（SGLT2i）的资格已扩大到心血管风险较低的糖尿病患者，但治疗益处是否因风险水平而异尚不清楚。
通过荟萃分析和荟萃回归研究，探讨不同风险水平的患者使用 GLP-1RA 和 SGLT2i 治疗在心血管和肾脏方面的获益是否存在差异。
我们通过 2022 年 11 月 7 日的 PubMed 进行了系统评价。
我们纳入了在成年患者中具有安全性或疗效终点数据的 GLP-1RA 和 SGLT2i 确证性随机试验报告。
提取死亡率、心血管和肾脏结局的风险比（HR）和事件发生率数据。
我们分析了 9 项 GLP-1RA 和 13 项 SGLT2i 试验，共纳入 154649 名患者。心血管死亡率（GLP-1RA 为 0.87，SGLT2i 为 0.86）、主要不良心血管事件（0.87 和 0.88）、心力衰竭（0.89 和 0.70）和肾脏（0.84 和 0.65）结局的汇总 HR 具有统计学意义。对于中风，GLP-1RA 有效（0.84），而 SGLT2i 无效（0.92）。对照臂心血管死亡率与 HR 之间的关联无统计学意义。在 SGLT2i 试验中，高风险（Pslope < 0.001）患者的心力衰竭 5 年绝对风险降低率（0.80-4.25%）增加到 11.6%。对于 GLP1-RAs，关联无统计学意义。
分析受到缺乏患者水平数据、终点定义一致性以及 GLP-1RA 试验心血管死亡率变化的限制。
新型糖尿病药物的相对疗效在基线心血管风险范围内保持不变，而绝对益处则随着风险的增加而增加，尤其是在心力衰竭方面。我们的研究结果表明，需要进行基线风险评估工具来识别绝对治疗益处的差异，从而改善决策。
