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 IgG(2), 
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 
hemoglobin was 0.11, 0.44, and 0.85% after 1, 2 (P = 0.017), and 3 (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.