Combining SGLT2i, GLP-1 RA Therapy Provides Complementary Cardiorenal Protection: Daily Dose

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Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

On July 12, 2024, we reported on findings from a study published in The Lancet Diabetes & Endocrinology that examined the effects of sodium glucose cotransporter-2 inhibitors (SGLT2i) used alone or in combination with glucagon-like peptide-1 receptor agonists (GLP-1 RA) on cardiovascular (CV) and renal outcomes among patients with type 2 diabetes (T2D).

The study

Researchers conducted a meta-analysis of 12 randomized double-blind placebo-controlled trials included in the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium (SMART-C) that enrolled only participants with T2D. They assessed 2 main CV outcomes, major adverse cardiovascular events (MACE) (a composite of nonfatal myocardial infarction, nonfatal stroke or CV death); and hospitalization for heart failure (HF) or CV death. The renal outcomes of interest were a composite outcome for chronic kidney disease (CKD) progression of a 40% or greater decline in eGFR, chronic dialysis, kidney transplantation or death from kidney failure; and rate of change in eGFR over time. Analysis of safety outcomes was assessed as well. The final cohort numbered 73 238; 82.1% had T2D and 4.2% were using GLP-1 RA at baseline.

The findings

Among participants treated with an SGLT2i alone or in combination with a GLP-1 RA, the risk of MACE was reduced by 11% and for hospitalization for either HF or CV death by 23%. When they evaluated the separate and combined effects on renal function, the risk of CKD progression dropped by 33% and the annual loss of renal function was slowed by nearly 60%.

Authors' comment

"SGLT2 inhibitors have clear protective effects against heart failure and chronic kidney disease, while GLP-1 receptor agonists can reduce the risk of heart attack, stroke, and also kidney disease…Our findings support using this combination to further improve outcomes in patients with type 2 diabetes who meet guideline recommendations for both therapies."

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