The blockade of interleukin-1 with anakinra improves glycemic control in patients with type 2 diabetes mellitus, according to results of a double-blind, parallel-group trial.
Researchers said improved glycemic control most likely was due to enhanced beta-cell secretory function (N. Engl. J. Med. 2007;356:1517–26).
“Further studies are needed to test higher doses of anakinra, to evaluate its long-term use, and to test interleukin-1 antagonists that have a prolonged half-life, with the aim of preventing beta-cell destruction and promoting beta-cell regeneration in type 2 diabetes,” wrote Dr. Claus Larsen, Steno Diabetes Center, Gentofte, Denmark, and associates.
In the 13-week trial, the researchers randomized 34 patients to 100 mg of anakinra (Kineret) once daily by subcutaneous self-administration, and 36 patients to placebo.
Glycated hemoglobin levels were significantly lower in the anakinra group after 4 weeks compared to the placebo group (an absolute reduction of 0.36%). The average absolute difference in glycated hemoglobin levels between baseline and 13 weeks was a reduction of 0.33% in the anakinra group and an increase of 0.13% in the placebo group.
Also at 13 weeks, beta-cell function increased in the anakinra group and decreased in the placebo group. The ratio of proinsulin to insulin was significantly lower in the anakinra group.
Levels of C-reactive protein and interleukin-6 were significantly lower after both 4 and 13 weeks in the anakinra group than in the placebo group.
Neither baseline values nor changes in levels of C-reactive protein or interleukin-6 were significantly correlated with changes in glycated hemoglobin levels in the anakinra group. This suggests that “reduced systemic inflammation did not play an important part in improved insulin secretion,” the researchers wrote.
However, “the response to anakinra might also be attributable to mildly improved insulin sensitivity resulting from reduced systemic inflammation,” Dr. Kristina Rother, of the National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md., suggested in an accompanying article (N. Engl. J. Med. 2007;356:1499–1501).
The researchers said the short duration and the lack of dose finding are weaknesses of the study, which was supported by several foundations, the Center for Clinical Studies at the University of Zürich, the European Union, and Novo Nordisk. The study drug was donated by Amgen.
Several of the authors report having an equity interest, receiving grant support, or being an employee of Novo Nordisk.