Common Diabetes Drug Does Not Increase Heart Failure Risks

Alogliptin (Nesina) did not increase risk of cardiovascular death or hospitalization due to heart failure (HF) in patients with type 2 diabetes and recent acute coronary syndrome, according to a new study.

The comparison of HF outcomes in 2,701 patients who received alogliptin and 2,679 patients treated with placebo showed rates of major adverse cardiac events were approximately 16% in both groups. A similar number of cardiovascular deaths and hospitalizations with initial HF — the study’s two main HF outcomes — occurred in both groups, according to the study, which also noted that alogliptin did not worsen pre-existing HF.

Just as importantly, said Dr. Faiez Zannad, of the University of Lorraine in France and lead author of the study, changes in levels of the amino acid Nt-ProBNP from baseline to 6 months and rates of diuretic therapy initiation — both important surrogate markers for HF onset — were comparable among alogliptin- and placebo-treated patients. He was also impressed that rates of cardiovascular death, hospitalization due to HF, and primary major adverse cardiac events endpoints were similar among patients with a history of HF, regardless of whether they were on alogliptin or placebo.

“It’s reassuring that, in such worse case scenarios, alogliptin was well tolerated with regard to cardiovascular outcomes, including heart failure,” commented Dr. Zannad.

The patients were participants in the EXAMINE trial, which was published in 2013 and showed that alogliptin did not increase risks of major adverse cardiac events, according to Dr. Zannad. But concerns about excessive rates of in-hospital HF in another DPP-4 inhibitor trial convinced his team of researchers to assess HF outcomes in this follow-up to the original EXAMINE trial.

Diabetes doubles event rates in patients with HF, which also increases the likelihood that HF will develop by 66%, said the researchers. Approximately half of the patients with type 2 diabetes will develop HF, noted the study, which said diabetics with HF are more likely to suffer adverse outcomes. Although antidiabetes medications have been shown to cause cardiovascular events, their true impact on HF outcomes is largely unknown.

Said Dr. Zannad, “For the time being, and until we have more data from other trials, if you have concerns about heart failure in patients with diabetes who need a DPP-4 inhibitor to optimize glycemic control, you’d rather have them on alogliptin.”

The study was published online in the journal The Lancet.

—Dan Cook

Reference:

1. Zannad F, Cannon CP, Cushman WC, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet. 2015 Mar 9. [Epub ahead of print]