Estimated lifetime benefit of novel pharmacological therapies in patients with type 2 diabetes and chronic kidney disease: A joint analysis of randomized controlled clinical trials.

Aim: 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). Materials and Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]