1. Effects of Gevokizumab on Glycemia and Inflammatory Markers in Type 2 Diabetes Featured Article: Claudia Cavelti-Weder, M.D., Andrea Babians-Brunner, M.D., Cornelia Keller, M.D., Marc A. Stahel, M.D., Malaika Kurz-Levin, M.D., Hany Zayed, Ph.D., Alan M. Solinger, M.D., Thomas Mandrup-Poulsen, M.D., Ph.D., Charles A. Dinarello, M.D., Marc Y. Donath, M.D. Diabetes Care Volume 35: 1654-1662 August, 2012

2. Study 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 Study evaluated safety and biological activity of gevokizumab in patients with type 2 diabetes Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

3. Study Design 98 patients randomly assigned to placebo (17 subjects) or gevokizumab (81 subjects) at increasing doses and dosing schedules Primary objective of study was to evaluate the safety profile of gevokizumab Secondary objectives were to assess pharmacokinetics for different dose levels, routes of administration, and regimens and to assess biological activity Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

4. Results Study drug well tolerated with no serious adverse events One hypoglycemic event requiring reduction of dosage of concomitant insulin treatment Clearance of gevokizumab was consistent with that for 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), mean placebo-corrected decrease in A1C was 0.11, 0.44, and 0.85% after 1, 2 (P= 0.017), and 3 (P = 0.049) months, respectively Also observed enhanced C-peptide secretion, increased insulin sensitivity, and a reduction in C-reactive protein and spontaneous and inducible cytokines Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

14. 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 Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662