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 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/ INTERPRETATION: A 4-month course of monthly canakinumab (50 mg) produced a numerical reduction of HbA(1c) in T2DM patients onmetformin, 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.
RCT Entities:
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 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-hPPG, 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 (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. TRIAL REGISTRATION: Registry: http://www.ClinicalTrials.gov, Registration No.: NCT00900146.
Authors: Scott J Pilla; Amy Q Quan; Emily L Germain-Lee; David B Hellmann; Nestoras N Mathioudakis Journal: Curr Diab Rep Date: 2016-10 Impact factor: 4.810