Anti-inflammatory canakinumab fails to prevent progression to diabetes

The anti-inflammatory drug canakinumab failed to halt the progression from prediabetes to diabetes, according to an analysis of the CANTOS trial presented March 11 at the American College of Cardiology’s annual scientific session.

The findings were published simultaneously in the Journal of the American College of Cardiology.

CANTOS randomized 10,061 patients with a prior myocardial infarction (MI) and elevated high-sensitivity C-reactive protein (hsCRP)—a measure of inflammation—to canakinumab once every three months or a placebo. The trial showed the medication significantly reduced major cardiovascular events in patients with and without diabetes, but a prespecified secondary analysis was planned to determine whether it could also reduce the cases of new-onset diabetes.

Nearly 5,000 patients enrolled in the trial had prediabetes and were followed for a median of 3.7 years. Similar to the findings from the entire cohort, this group experienced reductions in inflammation and cardiovascular events (14 percent).

However, prediabetic patients receiving canakinumab at doses of 50 mg, 150 mg or 300 mg were no less likely than placebo patients to develop diabetes. Incidence rates per 100 person-years were 4.2, 4.4 and 4.1, respectively, as the medication dose increased versus 4.2 in the placebo group.

“The results were surprising because we demonstrated an effect on blood glucose that didn’t translate into a reduced rate of type 2 diabetes diagnosis,” said lead author Brendan M. Everett, MD, MPH, who presented the findings at ACC.18. “It suggests that alternative inflammatory pathways may be more critical to the development of diabetes than inhibition of (interleukin)-1 beta, the specific mechanism we tested in this study.”