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American Heart Association, Circulation, 2023

DOI: 10.1161/circulationaha.123.067584

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Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Background: Sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone all individually reduce cardiovascular, kidney and mortality outcomes in patients with type 2 diabetes and albuminuria. However, the lifetime benefits of combination therapy with these medicines are not known. Methods: We used data from 2 SGLT2i trials (CANVAS and CREDENCE), 2 non-steroidal MRA trials (FIDELIO-DKD and FIGARO-DKD) and 8 GLP-1 RA trials to estimate the relative effects of combination therapy versus conventional care (renin-angiotensin system blockade and traditional risk factor control) on cardiovascular, kidney and mortality outcomes. Using actuarial methods, we then estimated absolute risk reductions with combination SGLT2i, GLP-1 RA and non-steroidal MRA in patients with type 2 diabetes and at lease moderately increased albuminuria (urinary albumin:creatinine ratio ≥30 mg/g) by applying estimated combination treatment effects to participants receiving conventional care in CANVAS and CREDENCE. Results: Compared to conventional care, combination SGLT2i, GLP-1 RA and non-steroidal MRA was associated with a hazard ratio of 0.65 (95% CI 0.55-0.76) for major adverse cardiovascular events (MACE; nonfatal myocardial infarction, nonfatal stroke or cardiovascular death). The corresponding estimated absolute risk reduction over 3 years was 4.4% (95% CI 3.0-5.7) with a number-needed-to-treat of 23 (95% CI 18-33). For a 50-year-old commencing combination therapy, estimated MACE event-free survival was 21.1 years compared to 17.9 years for conventional care (3.2 years gained, 95% CI 2.1-4.3). There were also projected gains in survival free from hospitalized heart failure (3.2 years, 95% CI 2.4-4.0), CKD progression (5.5 years, 95% CI 4.0-6.7), cardiovascular death (2.2 years, 95% CI 1.2-3.0) and all-cause death (2.4 years, 95% CI 1.4-3.4). Attenuated but clinically relevant gains in event-free survival were observed in analyses assuming 50% additive effects of combination therapy, including for MACE (2.4 years, 95% CI 1.1-3.5), CKD progression (4.5 years, 95% CI 2.8-5.9),) and all-cause death (1.8 years, 95% CI 0.7-2.8). Conclusions: In patients with type 2 diabetes and at least moderately increased albuminuria, combination treatment with SGLT2i, GLP-1 RA and non-steroidal MRA has the potential to afford relevant gains in cardiovascular and kidney event-free and overall survival.