Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
The George Institute for Global Health, Sydney, Australia.
Diabetes Obes Metab. 2023 Nov;25(11):3327-3336. doi: 10.1111/dom.15232. Epub 2023 Aug 14.
To estimate the lifetime benefit of a combination treatment of sodium-glucose co-transporter 2 (SGLT2) inhibitors and mineralocorticoid-receptor antagonists (MRA) in patients with type 2 diabetes and chronic kidney disease (CKD).
The cumulative effect of combination treatment was derived from trial-level estimates of the effect of an SGLT2 inhibitor (canagliflozin) and MRA (finerenone) from the CREDENCE (N = 4401) and FIDELIO (N = 5734) trials, respectively. The cumulative effect was applied to the control group of patients with type 2 diabetes in the DAPA-CKD trial (N = 1451) to estimate long-term gains in event-free and overall survival. The analysis was repeated in an observational study. The primary outcome was a composite endpoint of doubling of serum creatinine, end-stage kidney disease or death because of kidney failure.
The hazard ratio of combination treatment for the primary outcome was 0.50 [95% confidence interval (CI): 0.44, 0.57]. At age 50 years, the estimated event-free survival from the primary outcome was 16.7 years (95% CI: 18.1, 21.0) with combination treatment versus 10.0 years (95% CI: 6.8, 12.3) with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers resulting in an incremental gain of 6.7 years (95% CI: 5.5, 7.9). In an observational study, the estimated gain in event-free survival regarding primary outcome was 6.3 years (95% CI: 5.2, 7.3). In a conservative scenario, assuming low adherence (70% of the observed adherence) and less pronounced efficacy (70% of the observed efficacy with 2% yearly decline) of combination therapy, gain in event-free survival regarding primary outcome was 2.5 years (95% CI: 2.0, 2.9).
Combined disease-modifying treatment with an SGLT2 inhibitor and MRA in patients with type 2 diabetes and CKD may substantially increase the number of years free from kidney failure and mortality.
评估钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂和盐皮质激素受体拮抗剂（MRA）联合治疗 2 型糖尿病合并慢性肾脏病（CKD）患者的终生获益。
从 CREDENCE（n=4401）和 FIDELIO（n=5734）试验中分别获得 SGLT2 抑制剂（卡格列净）和 MRA（非奈利酮）的试验水平估计值，得出联合治疗的累积效应。将累积效应应用于 DAPA-CKD 试验（n=1451）中 2 型糖尿病患者的对照组，以估计无事件和总体生存率的长期获益。该分析在一项观察性研究中重复进行。主要结局是血清肌酐加倍、终末期肾病或因肾衰竭导致的死亡的复合终点。
联合治疗的主要结局的风险比为 0.50（95%置信区间：0.44，0.57）。在 50 岁时，联合治疗的无事件主要结局生存率为 16.7 年（95%置信区间：18.1，21.0），而血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂的生存率为 10.0 年（95%置信区间：6.8，12.3），联合治疗的获益为 6.7 年（95%置信区间：5.5，7.9）。在一项观察性研究中，主要结局的无事件生存率估计获益为 6.3 年（95%置信区间：5.2，7.3）。在保守情景下，假设联合治疗的依从性较低（观察到的依从性的 70%）和疗效不那么明显（观察到的疗效的 70%，每年下降 2%），主要结局的无事件生存率获益为 2.5 年（95%置信区间：2.0，2.9）。
在 2 型糖尿病合并 CKD 患者中，联合使用 SGLT2 抑制剂和 MRA 进行疾病修饰治疗可能会显著增加免于肾衰竭和死亡的年数。
