Physicians' Academy for Cardiovascular Education

IL-1β inhibitor does not prevent new onset type 2 diabetes

Anti-Inflammatory Therapy with Canakinumab and Incident Type 2 Diabetes: A Pre-Specified Key Secondary Endpoint of the CANTOS Trial

Presented at ACC.18 by Brendan Everett (Boston, MA, USA)

News - Mar. 12, 2018

Introduction and methods

Data suggest a pathologic role for subclinical inflammation in peripheral insulin resistance, impaired insulin secretion and the development of type 2 diabetes (T2DM). This may in part be mediated by induction of the NLRP3 inflammasome and activation of IL-1β. Treatment with anakinra, an IL-1 receptor antagonist, showed improvements in beta cell function, peripheral glucose sensitivity, reductions in HbA1c in 70 T2DM patients [1].

The monoclonal antibody targeting IL-1β canakinumab, was evaluated in post-MI patients for the reduction of CV events. In the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), stable post-MI patients with hsCRP ≥2 mg/mL were randomized to placebo or one of three doses (50, 150, 300 mg) canakinumab. Canakinumab reduced the primary endpoint, a composite of non-fatal MI, non-fatal stroke, and CV death (MACE).

In this sub-analysis of CANTOS, the effect of canakinumab on the risk of new onset T2DM was evaluated. Participants were monitored for the development of newly diagnosed T2DM, defined as two measures within 6 weeks of either HbA1c ≥6.5% or fasting plasma glucose ≥126 mg/dL, or by the institution of antihyperglycemic therapy.

Main results


Treatment with the IL-1β inhibitor canakinumab did not prevent the progression from pre-diabetes to diabetes in post-MI patients with hsCRP ≥2 mg/mL.

In a press release the study’s lead author dr. Everett said: “The results were surprising, because we demonstrated there was an effect on blood glucose that didn’t translate into a reduced rate of type 2 diabetes diagnosis. It suggests that alternative inflammatory pathways may be more critical to the development of diabetes than inhibition of interleukin-1 beta, which was the specific mechanism we tested in this study.”


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Our coverage of ACC.18 is based on the information provided during the congress.

This study was published simultaneously in JACC View this video in which Brendan Everett discusses the CANTOS-diabetes results

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