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

Hiddo J. L. Heerspink*, Priya Vart, Niels Jongs, Brendon L. Neuen, George Bakris, Brian Claggett, Muthiah Vaduganathan, Finnian McCausland, Kieran F. Docherty, Pardeep S. Jhund, Scott D. Solomon, Vlado Perkovic, John J.V. McMurray

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)3327-3336
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume25
Issue number11
DOIs
Publication statusPublished - Nov-2023

Keywords

  • chronic kidney disease
  • mineralocorticoid receptor antagonist
  • SGLT2 inhibitor
  • type 2 diabetes

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