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

Abstract 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.