The anti-inflammatory drug canakinumab had no effect on progression of prediabetes to diabetes, according to the secondary endpoint results of the CANTOS trial presented by Brendan M. Everett, MD, MPH, FACC, on Sunday, March 11 in a Late-Breaking Clinical Trial session at ACC.18 in Orlando, FL.

A total of 10,061 patients with prior myocardial infarction (MI) and elevated high-sensitivity C-reactive protein (hsCRP) were randomized to canakinumab once every three months or placebo. Primary endpoint analysis found that canakinumab significantly reduced major cardiovascular events in patients with and without diabetes. A prespecified analysis also evaluated the effect of canakinumab on the risk of new-onset type 2 diabetes in patients with prediabetes.

A total of 4,960 patients with prediabetes at trial entry received canakinumab (50, 150 or 300  mg) for a median of 3.7 years. The effects of canakinumab on the inflammatory markers, interleukin-6 (IL-6) and hsCRP; progression to diabetes; and HbA1c were evaluated.

Significant, dose-dependent reductions from baseline in inflammatory markers were observed in patients with prediabetes receiving canakinumab versus placebo. The median percent reductions in hsCRP after the first canakinumab dose for the 50, 150 and 300 mg dose groups were –49.2, –61.5, and –67.1, respectively. For IL-6, the median percent reductions for the three dose groups were –25.7, –37.4 and –43.4, respectively.

Despite these reductions, canakinumab did not reduce the rate of new-onset diabetes. In the 50, 150, and 300 mg dose groups, the incidence of new-onset diabetes was 4.24, 4.35 and 4.12, respectively, compared with 4.20 in the placebo group. Combined analysis of the three dose groups found no significant difference compared with placebo. Patients with prediabetes had significant reductions in HbA1c over the first six to nine months, but there was no difference at 48 months.

"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 Everett. "It suggests that alternative inflammatory pathways may be more critical to the development of diabetes than inhibition of IL-1 beta, the specific mechanism we tested in this study."

Keywords: ACC18, ACC Annual Scientific Session, Primary Prevention, Insulin, Diabetes Mellitus, Type 2, C-Reactive Protein, Interleukin-1beta, Insulin Resistance, Glycated Hemoglobin A, Blood Glucose, Research Personnel, Fasting, Hypoglycemic Agents, Antibodies, Monoclonal, Anti-Inflammatory Agents, Thrombosis, Inflammation, Myocardial Infarction, Stroke, Outcome Assessment, Health Care, Clinical Protocols

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