Impact of interleukin-1β antibody (canakinumab) on glycaemic indicators in patients with type 2 diabetes mellitus: Results of secondary endpoints from a randomized, placebo-controlled trial

Abstract Aims/hypothesis This study was conducted to determine the optimal monthly subcutaneous dose of canakinumab (a human monoclonal anti-human IL-1β antibody) needed to improve glucose control in metformin-treated patients with type 2 diabetes mellitus (T2DM). Methods This was a parallel-group, randomized, double-blind, multicentre, placebo-controlled study designed to assess the effect on HbA 1c and the safety/tolerability of four monthly doses of canakinumab (5, 15, 50, or 150mg) as an add-on to metformin over 4 months. Results Patients ( n =551; mean age 54.1 years; mean baseline HbA 1c 7.4%) were randomized and treated in a double-blind fashion to canakinumab 5mg ( n =93), 15mg ( n =95), 50mg ( n =92), 150mg ( n =92) or placebo ( n =179) monthly. There was no dose response detected between active canakinumab doses, but all doses numerically lowered HbA 1c (primary endpoint) from baseline between 0.19% and 0.31% (placebo-unadjusted), with maximal effect noted in the 50mg dose of canakinumab (−0.18% difference vs placebo; multiplicity-adjusted, P =0.13902) as reported earlier (Ridker et al., 2012). No other glycaemic control parameters (FPG, fasting insulin, plasma glucose AUC 0–4h , 2-h PPG, peak glucose, C-peptide AUC 0–4h , peak C-peptide, insulin AUC 0–4h , peak insulin, ISR 0–2h , HOMA-β and HOMA-IR) showed any meaningful changes by canakinumab therapy. Canakinumab treatment was safe and well tolerated. There were no relevant differences in adverse events between the canakinumab and placebo groups. Conclusions/interpretation A 4-month course of monthly canakinumab (50mg) produced a numerical reduction of HbA 1c in T2DM patients on metformin, potentially by improving beta-cell function. The safety and tolerability profile of canakinumab was consistent with prior trials. Trial registration Registry: http://www.ClinicalTrials.gov, Registration No.: NCT00900146