TY - JOUR
T1 - Effects of Gevokizumab on Glycemia and Inflammatory Markers in Type 2 Diabetes
AU - Cavelti-Weder, Claudia
AU - Babians-Brunner, Andrea
AU - Keller, Cornelia
AU - Stahel, Marc A
AU - Kurz-Levin, Malaika
AU - Zayed, Hany
AU - Solinger, Alan M
AU - Mandrup-Poulsen, Thomas
AU - Dinarello, Charles A
AU - Donath, Marc Y
PY - 2012/8
Y1 - 2012/8
N2 - OBJECTIVE - Metabolic activation of the innate immune system governed by interleukin (IL)-1β contributes to β-cell failure in type 2 diabetes. Gevokizumab is a novel, human-engineered monoclonal anti-IL-1β antibody. We evaluated the safety and biological activity of gevokizumab in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - In a placebo-controlled, dose-escalation study, a total of 98 patients were randomly assigned to placebo (17 subjects) or gevokizumab (81 subjects) at increasing doses and dosing schedules. The primary objective of the study was to evaluate the safety profile of gevokizumab in type 2 diabetes. The secondary objectives were to assess pharmacokinetics for different dose levels, routes of administration, and regimens and to assess biological activity. RESULTS - The study drug was well tolerated with no serious adverse events. There was one hypoglycemic event whereupon concomitant insulin treatment had to be reduced. Clearance of gevokizumab was consistent with that for a human IgG2, with a half-life of 22 days. In the combined intermediate-dose group (single doses of 0.03 and 0.1 mg/kg), the mean placebo-corrected decrease in glycated hemoglobinwas 0.11, 0.44, and 0.85%after 1, 2 (P= 0.017), and3 (P = 0.049) months, respectively, along with enhanced C-peptide secretion, increased insulin sensitivity, and a reduction in C-reactive protein and spontaneous and inducible cytokines. CONCLUSIONS - This novel IL-1β-neutralizing antibody improved glycemia, possibly via restored insulin production and action, and reduced inflammation in patients with type 2 diabetes. This therapeutic agent may be able to be used on a once-every-month or longer schedule.
AB - OBJECTIVE - Metabolic activation of the innate immune system governed by interleukin (IL)-1β contributes to β-cell failure in type 2 diabetes. Gevokizumab is a novel, human-engineered monoclonal anti-IL-1β antibody. We evaluated the safety and biological activity of gevokizumab in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - In a placebo-controlled, dose-escalation study, a total of 98 patients were randomly assigned to placebo (17 subjects) or gevokizumab (81 subjects) at increasing doses and dosing schedules. The primary objective of the study was to evaluate the safety profile of gevokizumab in type 2 diabetes. The secondary objectives were to assess pharmacokinetics for different dose levels, routes of administration, and regimens and to assess biological activity. RESULTS - The study drug was well tolerated with no serious adverse events. There was one hypoglycemic event whereupon concomitant insulin treatment had to be reduced. Clearance of gevokizumab was consistent with that for a human IgG2, with a half-life of 22 days. In the combined intermediate-dose group (single doses of 0.03 and 0.1 mg/kg), the mean placebo-corrected decrease in glycated hemoglobinwas 0.11, 0.44, and 0.85%after 1, 2 (P= 0.017), and3 (P = 0.049) months, respectively, along with enhanced C-peptide secretion, increased insulin sensitivity, and a reduction in C-reactive protein and spontaneous and inducible cytokines. CONCLUSIONS - This novel IL-1β-neutralizing antibody improved glycemia, possibly via restored insulin production and action, and reduced inflammation in patients with type 2 diabetes. This therapeutic agent may be able to be used on a once-every-month or longer schedule.
U2 - 10.2337/dc11-2219
DO - 10.2337/dc11-2219
M3 - Journal article
C2 - 22699287
SN - 0149-5992
JO - Diabetes Care
JF - Diabetes Care
ER -
