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

Heerspink, H. J. L. et al. (2023) 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. Diabetes, Obesity and Metabolism, 25(11), pp. 3327-3336. (doi: 10.1111/dom.15232) (PMID:37580309)

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.

• Item Type: Articles
• Additional Information: HJL Heerspink is supported by a VIDI grant from the Netherlands Organization for Scientific Research (917.15.306) and by a grant from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115974. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation pro-gramme and EFPIA. J.J.V.M. is supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Docherty, Dr Kieran and Jhund, Professor Pardeep and McMurray, Professor John
• Authors: Heerspink, H. J. L., Vart, P., Jongs, N., Neuen, B. L., Bakris, G., Claggett, B., Vaduganathan, M., McCausland, F., Docherty, K. F., Jhund, P. S.,, Solomon, S. D., Perkovic, V., and McMurray, J. J. V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Diabetes, Obesity and Metabolism
• Publisher: Wiley
• ISSN: 1462-8902
• ISSN (Online): 1463-1326
• Published Online: 14 August 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Diabetes, Obesity and Metabolism 25(11):3327-3336
• Publisher Policy: Reproduced under a Creative Commons license

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303944		BHF Centre of Excellence	Colin Berry	British Heart Foundation (BHF)	RE/18/6/34217	SCMH - Cardiovascular & Metabolic Health