番茄社区

The DPP-4 inhibitor saxagliptin (Onglyza) appears to be safe in renal patients, researchers reported.

In an analysis of data from the SAVOR-TIMI 53 study, the drug didn't affect the risk of a composite of cardiovascular outcomes regardless of renal function, , of Brigham and Women's Hospital, and colleagues .

It also appeared to halt progression of diabetic nephropathy in most renal patients -- but there was an increased risk of hospitalization for heart failure in those with moderate renal impairment, the researchers said.

Since there are so few data on choice of anti-hyperglycemic medication for diabetes patients with renal impairment, researchers said the results are reassuring.

But Naveed Sattar, MD, PhD, of Glasgow University, who was not involved in the study, said the results aren't clear.

"In the strictest terms, the stats suggest one cannot differentiate with any confidence the effects on this outcome by the three eGFR groups," Sattar told 番茄社区. "I think the data for severe renal failure is too wide in confidence interval to tell us what the risks are, and the absolute risks in this group were high in both groups, thus more potential for noise."

"I think we need to wait for TECOS to give us anything more meaningful," Sattar added.

SAVOR was one of two trials, along with EXAMINE, that examined the cardiovascular safety of new diabetes agents. The trials were done to comply with FDA requirements imposed after problems with cardiac safety were seen with other classes of diabetes medications such as thiazolidinediones.

SAVOR was the larger trial, enrolling 16,492 patients who were followed for about 2 years, while , was done in fewer patients (total 5,380) who were also sicker -- all of them had to have had a recent acute coronary syndrome.

Both studies found that these drugs neither reduced or increased the risk of cardiovascular events overall -- although there was a significant 27% higher risk of hospitalizations for heart failure in patients on saxagliptin in the SAVOR study.

To focus on the effect of saxagliptin according to baseline renal function, Scirica and colleagues conducted a secondary analysis of SAVOR data. Median eGFR among participants was 71.7 mL/min.

Moderate renal impairment was defined as an eGFR of 30 to 50 mL/min, and severe renal impairment was classified by an eGFR below 30 mL/min.

With median follow-up of 2 years, the researchers saw no difference in the risk of primary and secondary composite endpoints between saxagliptin and placebo, irrespective of renal function.

The risk of hospitalization for heart failure, however, was significantly increased among patients with an eGFR of 30 to 50 mL/min who were taking saxagliptin (HR 1.46, 95% CI 1.07 to 2.00).

But the frequency of progressive diabetic nephropathy was significantly reduced with saxagliptin for patients with normal or mildly impaired renal function (P<0.0001) and moderate-to-severe renal impairment (P=0.041) -- although the effect did not hold for those with severe renal impairment.

And the drug did its antiglycemic job, lowering HbA1c even in renal patients, the researchers noted.

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