Kidney, CV outcomes similar for SGLT2 inhibition vs. GLP-1s for diabetes
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Key takeaways:
- SGLT2 inhibition may confer similar kidney and CV outcomes vs. GLP-1 receptor agonists for diabetes.
- Results were consistent regardless of CKD status, but SGLT2 inhibitors were tied to preserved renal function.
SGLT2 inhibitors were associated with similar renal and CV outcomes vs. GLP-1 receptor agonists for patients with diabetes, regardless of chronic kidney disease status, researchers reported.
Although SGLT2 inhibitors were associated higher risk for genital mycotic infections compared with GLP-1s, SGLT2 inhibition may better preserve renal function, according to a study published in the Journal of the American College of Cardiology.
“Consensus guidelines recommend SGLT2 inhibitors and GLP-1 receptor agonists as first- and second-line antiglycemic adjuncts to metformin, respectively, especially in people with established kidney or cardiovascular disease. Despite some overlap, these therapies may exert distinct cardiorenal effects,” Daniel Edmonston, MD, MHS, nephrologist at the Duke Nephrology Clinic and member in the Duke Clinical Research Institute, and colleagues wrote. “Both therapies improve cardiovascular outcomes, but GLP-1 receptor agonists primarily reduce the risk of major adverse cardiovascular events (MACE), whereas SGLT2 inhibitors more substantially decrease risk of heart failure hospitalization. Both therapies also improve kidney outcomes, although it remains unclear whether GLP-1 receptor agonists improve outcomes beyond albuminuria. Direct comparisons between these treatment options ... could further discern differences in the cardiorenal effects between these agents and potentially guide individualized treatment decisions not captured by current guideline recommendations.”
Edmonston and colleagues used electronic health record data from 20 large U.S. health systems participating in the National Patient-Centered Clinical Research Network to compare kidney and CV outcomes between SGLT2 inhibitors and GLP-1 receptor agonists in patients with diabetes, with or without chronic kidney disease (CKD), from 2015 to 2020.
Propensity score overlap weighting was used to assess for differences in the primary kidney composite outcome of sustained 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease or all-cause mortality, as well as CV and safety outcomes.
The analysis included 35,004 patients who started SGLT2 inhibition and 47,268 who started a GLP-1 receptor agonist (median age, 59 years; 71% white; 53% women). The median HbA1c was 8.2%; CKD was present in 19.6% of the cohort; and median eGFR was 81.4 mL/min/1.73 m2.
During a median follow-up of 1.2 years, risk for the primary composite outcome did not differ significantly between SGLT2 inhibitors and GLP-1 receptor agonists (HR = 0.91; 95% CI, 0.81-1.02) and neither did mortality (HR = 1.08; 95% CI, 0.92-1.27), a composite of stroke, MI or death (HR = 1.03; 95% CI, 0.93-1.14) and HF hospitalization (HR = 0.95; 95% CI, 0.8-1.13); however, SGLT2 inhibition was associated with lower risk for 40% eGFR decline (HR = 0.77; 95% CI, 0.65-0.91).
These findings were consistent regardless of CKD status.
SGLT2 inhibitors were associated with a significantly greater risk for genital mycotic infection compared with GLP-1 receptor agonists (HR = 1.71; 1.61-1.82; P < .001), according to the study.
“Given the large amount of overlapping cardiorenal benefits from these medications in this study, a combination of SGLT2 inhibitors and GLP-1 receptor agonist therapy is an important consideration,” they wrote. “Because these agents differ with regard to glycemic control, weight loss, and select kidney and cardiovascular outcomes, combination therapy may take advantage of these complementing effects.”
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