IL-1 beta inhibition does not prevent diabetes
medwireNews: Interleukin-1 beta (IL-1ß) inhibition with canakinumab does not prevent the development of type 2 diabetes, a secondary analysis of data from CANTOS shows.
The findings were contrary to the researchers’ hypothesis and “have several important implications for both clinical practice and pathophysiology,” they write in the Journal of the American College of Cardiology.
Brendan Everett (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and co-investigators say that although diabetes incidence was not reduced, it was also not increased, which is reassuring for current strategies that use inflammation inhibition to treat atherosclerosis in patients who are potentially at increased risk for diabetes.
They add: “While inflammation remains important for both [cardiovascular disease and diabetes], data from CANTOS suggest divergence of inflammatory pathways in [each].”
At baseline, 4057 (40.3%) CANTOS participants had type 2 diabetes, 4960 (49.3%) had prediabetes, and 1044 (10.4%) had normal glucose levels. All participants had prior myocardial infarction and a high-sensitivity C-reactive protein (hsCRP) level of at least 2 mg/L.
During a median 3.7 years of follow-up, the incidence of diabetes among those without it at baseline increased significantly with increasing baseline hsCRP level, from 3.2 cases per 100 person–years in the lowest tertile to 4.1 and 4.4 cases per 100 person–years in the middle and top tertiles, respectively.
Baseline IL-6 level also significantly predicted the onset of diabetes, with those in the highest baseline tertile almost twice as likely to develop the condition as those in the lowest tertile.
Following treatment with canakinumab, there were substantial reductions in both hsCRP (median 49–67%) and IL-6 (median 26–43%) levels, but these were not accompanied by reductions in new-onset diabetes incidence. Specifically, the rates in the placebo, 50 mg, 150 mg, and 300 mg canakinumab groups were 4.2, 4.2, 4.4, and 4.1 cases per 100 person–years, respectively.
The researchers did observe a “modest but significant” reduction in glycated hemoglobin during the first 6–9 months of treatment with canakinumab, but this was attenuated over time, leaving no difference from baseline at 2 years.
The efficacy of canakinumab for preventing major cardiovascular events was similar among patients with diabetes, prediabetes, and normal blood glucose at baseline, with nonsignificant risk reductions of 10%, 14%, and 19%, respectively, for all doses of canakinumab versus placebo.
Everett and team also note that among patients with diabetes, canakinumab was not associated with an increased risk for infection compared with placebo, but was associated with a significantly increased risk for fatal infection (hazard ratio=1.86), in line with the original findings of the CANTOS trial.
By Laura Cowen
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