Physicians' Academy for Cardiovascular Education

Combination of SGLT2i and nonsteroidal MRA improves estimated event-free survival in T2D and CKD

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

Literature - Heerspink HJL, Vart P, Jongs N, et al. - Diabetes Obes Metab. 2023 Nov;25(11):3327-3336. doi: 10.1111/dom.15232

Introduction and methods


SGLT2 inhibitors and the selective, nonsteroidal MRA finerenone have been shown to improve CV and renal outcomes in patients with both T2D and CKD [1-3]. In addition, a recent RCT showed an additive effect on albuminuria and blood pressure with combination treatment with an SGLT2 inhibitor and MRA in CKD patients with and without T2D compared with either drug alone [4]. Still, the implementation of these therapies in routine practice is low.

Aim of the study

The authors estimated the lifetime benefit of SGLT2 inhibitor and nonsteroidal MRA combination treatment versus conventional therapy in patients with T2D and CKD.


The authors used overall trial-level estimates from 2 pivotal placebo-controlled phase 3 RCTs in which the efficacy and safety of canagliflozin (CREDENCE trial; n=4401) or finerenone (FIDELIO-CKD trial, n=5674) were assessed [1,3]. To estimate long-term gains in event-free and overall survival, data of T2D patients in the placebo group of the DAPA-CKD trial (n=1451) were used [2]. All participants in these trials were prescribed an ACEi or ARB.

To derive combined treatment effects and project substantial gains in event-free survival, previously validated methods from cardiology trials were applied. To assess the robustness of the results in a nonclinical setting, data from the observational CRIC (Chronic Renal Insufficiency Cohort) Study were used [5].


The primary endpoint was a composite outcome of sustained doubling of serum creatinine, end-stage kidney disease (ESKD; defined as sustained eGFR ≤15 mL/min per 1.73 m², initiation of dialysis for ≥30 days, or kidney transplantation), or death because of kidney failure. The secondary endpoint was ESKD. Additional endpoints were HF hospitalization and all-cause mortality.

Main results


This study estimated the lifetime benefit of SGLT2 inhibitor and nonsteroidal MRA combination treatment versus conventional therapy. Analysis of pivotal RCT data showed that combination treatment with canagliflozin and finerenone reduced the risk of adverse renal outcomes by 50% in patients with T2D and CKD compared with conventional treatment (ACEi or ARB) only. For those starting combination treatment at age 50 years, the estimated gain in survival free of this primary composite outcome was ~7 years, whereas the estimated gain in overall survival was 2 years. A real-world scenario assumed an estimated gain in event-free survival of the primary endpoint of 2.5 years.

The authors believe their findings could aid patients and their physicians. “Because the progression of diabetic kidney disease takes many years and trials are conducted over a follow-up shorter than life expectancy of patients, projections of lifetime application beyond the duration of a trial may help in communicating potential lifetime benefits and implementation of new therapies.”


Show references

Find this article online at Diabetes Obes Metab.

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