Combination treatment with SGLT2 inhibitors and MRAs yielded an estimated hazard ratio of 0.50 (95% CI 0.44-0.57) for doubling of serum creatinine, ESKD, or kidney death.
Meta-Analysis (n=11,586)
Does combination treatment with SGLT2 inhibitors and MRAs improve event-free survival from kidney failure in patients with type 2 diabetes and CKD?
Combined 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 compared to ACEi/ARB alone.
Effect estimate: HR 0.50 (95% CI 0.44-0.57)
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.
Heerspink et al. (Mon,) conducted a meta-analysis in Type 2 diabetes and chronic kidney disease (n=11,586). Combination treatment of SGLT2 inhibitors and MRA vs. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was evaluated on Composite endpoint of doubling of serum creatinine, end-stage kidney disease or death because of kidney failure (HR 0.50, 95% CI 0.44-0.57). Combination treatment with SGLT2 inhibitors and MRAs yielded an estimated hazard ratio of 0.50 (95% CI 0.44-0.57) for doubling of serum creatinine, ESKD, or kidney death.