Canagliflozin mediates biomarkers prognostic of cardiorenal risk in diabetes, albuminuria
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Key takeaways:
- Canagliflozin reduced several cardiorenal biomarkers in patients with type 2 diabetes and CKD.
- End-stage kidney disease, creatinine level and renal or CV death were lower in the canagliflozin arm vs. placebo.
Blood tests showed that canagliflozin plus standard care lowered biomarkers levels associated with chronic kidney disease and CVD events in patients with diabetes and albuminuria vs. placebo, researchers reported.
The post hoc analysis of the CREDENCE trial was published in Circulation.
“High levels of certain biomarkers are indicators of heart and kidney complications and may help predict future risk of disease progression,” James Januzzi, MD, the Hutter Family Professor of Medicine at Harvard Medical School, cardiologist at Massachusetts General Hospital and director of heart failure and biomarker trials at the Baim Institute for Clinical Research in Boston, said in a press release. “Treatment with canagliflozin, a sodium-glucose cotransporter 2 inhibitor, lowered biomarker levels and reduced the risk of hospitalization for heart failure and other heart complications in people at the highest risk.”
The CREDENCE trial
For the CREDENCE trial, researchers evaluated the efficacy and safety of canagliflozin (Invokana, Janssen) plus standard care for the prevention of chronic kidney disease (CKD) and CVD compared with placebo in approximately 4,400 patients with type 2 diabetes, estimated glomerular filtration rate of 30 mL/min/1.73 m2 to 90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of 300 mg/g to 5,000 mg/g.
As Healio previously reported, the CREDENCE clinical trial was halted early due to reaching its prespecified efficacy criteria.
For the present study, researchers evaluated the effect of canagliflozin on biomarkers including N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin T, growth differentiation factor-15 and insulin-like growth factor binding protein 7 among 2,627 CREDENCE trial participants.
The primary outcome was a composite of end-stage kidney disease, doubling of the serum creatinine level or renal or CV death.
Blood biomarkers and CVD, renal risk
The median baseline concentration of each biomarker was generally elevated compared with health reference populations:
- NT-proBNP, 180 ng/L;
- high-sensitivity cardiac troponin T, 19 ng/L;
- growth differentiation factor-15, 2,595 ng/L; and
- insulin-like growth factor binding protein 7, 121.8 ng/mL.
At 1 year, all biomarker levels increased 6% to 29% in the placebo arm compared with 3% to 10% in the canagliflozin arm (P for all < .01), according to the study.
Using a multi-marker blood panel, the researchers reported that individuals in highest tertile (HR = 4.01; 95% CI, 2.52-6.35) and middle tertile (HR = 2.39; 95% CI, 1.48-3.87) of serum biomarker levels had greater risk for the primary composite outcome compared with those in the lowest tertile.
Moreover, a 50% increase at 1 year in NT-proBNP (HR = 1.11; 95% CI, 1.08-1.15), high-sensitivity cardiac troponin T (HR = 1.86; 95% CI, 1.64-2.1), growth differentiation factor-15 (HR = 1.45; 95% CI, 1.24-1.7) and insulin-like growth factor binding protein 7 (HR = 3.76; 95% CI, 2.54-5.56) were all associated with increased risk for the primary composite outcome.
“It was reassuring to discover that canagliflozin helped reduce risks the most in people with the highest chances for complications. Future studies are needed to better understand how type 2 diabetes in conjunction with kidney disease develops and progresses so that we may initiate lifesaving therapies earlier, before symptoms of heart and kidney disease have occurred,” Januzzi said in the release. “Given that the American Heart Association/American College of Cardiology and the American Diabetes Association now all recommend measurement of biomarkers to enhance ability to predict risk in persons with type 2 diabetes, these results may considerably extend the reach of biomarker-based testing, refining accuracy even further.”
Reference:
- Simple blood test may predict future heart, kidney risk for people with type 2 diabetes. https://newsroom.heart.org/news/simple-blood-test-may-predict-future-heart-kidney-risk-for-people-with-type-2-diabetes. Published Aug. 21, 2023. Accessed Aug. 21, 2023.
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