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.
OBJECTIVE
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 150 mg) 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 5 mg (n=93), 15 mg (n=95), 50 mg (n=92), 150 mg (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
A 4-month course of monthly canakinumab (50 mg) 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.


BACKGROUND
Registry: http://www.ClinicalTrials.gov, Registration No.: NCT00900146.
Klinikum Hannover Nordstadt, Hannover, Lower Saxony, Germany.
J
J
Hensen
C P
CP
Howard
V
V
Walter
T
T
Thuren
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis / Q000187:drug effects; D038321:Glycemic Index; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D008687:Metformin; C541220:canakinumab
Anticorps monoclonal; Canakinumab; Diabetes mellitus; Diabète sucré; Interleukin-1β; Interleukine-1β; Metformin; Metformine; Monoclonal antibody