Dapagliflozin Benefits in Type-2 Diabetes Consistent Across Kidney Function Groups

By David Douglas

April 23, 2021

NEW YORK (Reuters Health) - The sodium-glucose co-transporter 2 inhibitor (SGLT2i) dapagliflozin has consistent cardiovascular benefits across baseline kidney-function and albuminuria levels in high-risk patients with type-2 diabetes mellitus (T2DM), according to a secondary analysis of the DECLARE-TIMI 58 trial.

"Dapagliflozin consistently reduced the relative risk of cardiovascular events irrespective of baseline estimated glomerular filtration rate (eGFR) and albuminuria status in a broad population of patients with T2DM," Dr. Thomas A. Zelniker of the Medical University of Vienna, in Austria, told Reuters Health by email.

"However," he added, "patients with both reduced eGFR and albuminuria derived significantly greater absolute risk reduction for the composite of cardiovascular death and hospitalizations for heart failure, reflecting a consistent effect in the context of their higher baseline risk."

In their paper in JAMA Cardiology, Dr. Zelniker and colleagues note that SGLT2is promote urinary glucose excretion and reduce the risk for cardiovascular death and hospitalizations for heart failure in patients with T2DM. However, the researcher said, "The extent of increased glucosuria and, therefore, the glucose-lowering efficacy of SGLT2i is attenuated in patients with worse kidney function."

To examine what impact this might have the researchers conducted a prespecified analysis of the DECLARE-TIMI 58 trial, a cardiovascular-outcome trial that studied the effect of dapagliflozin versus placebo in more than 17,000 patients who had or were at risk for atherosclerotic cardiovascular disease.

Patients were categorized according to prespecified subgroups of baseline eGFR of below 60 mL/min/1.73m2 versus greater, urinary-albumin-to-creatinine ratio (UACR) of below 30mg/g versus greater, and the number of chronic kidney disease (CKD) markers (0, 1, or 2).

The clinical efficacy of dapagliflozin was generally consistent across kidney-function subgroups, with no significant interaction seen for the composite of cardiovascular (CV) death and heart-failure hospitalization (HHF) or for major adverse cardiovascular events.

"However, given their higher baseline risk, the magnitude of the absolute risk difference was significantly higher for patients with more markers of CKD (-0.5%for 0 markers, -1.0%for 1 marker, and -8.3%for 2 markers; P = .02 for interaction for absolute risk difference)," the researchers report. "These findings suggest that 13 patients with both eGFR lower than 60 mL/min/1.73m2 and UACR of at least 30mg/g need to be treated for 4 years to prevent 1 event of the composite of CV death or HHF."

The researchers note that the numbers of amputations, cases of diabetic ketoacidosis, fractures, and major hypoglycemic events were balanced or numerically lower with dapagliflozin compared with placebo for patients with an eGFR below 60 mL/min/1.73m2 and an UACR of 30mg/g or higher.

Overall, concluded Dr. Zelniker, "These data indicate an apparent disconnect between cardiovascular efficacy and measures of glucose control and suggest that SGLT2i should be considered in patients with T2DM and chronic kidney disease for the reduction of cardiovascular events."

The trial was funded by AstraZeneca. Dr. Zelniker reports financial ties to the company.

SOURCE: https://bit.ly/3sCSGf7 JAMA Cardiology, online April 14, 2021.