Effect of anti-IL-1β antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes: Results of a randomized, placebo-controlled trial

Aila Rissanen, C. P. Howard, J. Botha, T. Thuren, Joseph Proietto, Geoffrey Nicholson, Peter Colman, Ronnie Aronson, Ronald Goldenberg, Hasnain Khandwala, Richard Dumas, Jean Pierre Hallé, Aila Rissanen, Sirkka Keinanen-Kiukaanniemi, Merja Laine, Helmut Anderten, Uwe Boeckmann, Julia Chevts, Winfried Keuthage, Klaus FunkeAndrei Khariouzov, Joerg Luedemann, Stephan Martin, Thorsten Rau, Reinhold Schneider, Gerhard Steinmaier, Ulrike Venschott-Jordan, Ingo Zeissig, Sunil Jain, Aarti Dharskar, Sanjay Reddy, Sathyanarayana Srikanta, Kav Subrahmanyam, V. Mohan, Rajendran K. Nair, Shailaja Kale, Francesco Dotta, Antonio Pontiroli, Giorgio Pagani, Andrea Giaccari, Esio Ronchi, Piermarco Piatti, Giorgio Luciano Viviani, Robert Anderson, Charles M. Arena, Robert Burton, James Lane, Andrew Lewin, Michael Lillestol, Jerry R. Mitchell, Bryce Palchick, Julio Rosenstock, Bret Wittmer, Robert Lipetz

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Aims: Evaluate anti-interleukin-1β (IL-1β) antibody, canakinumab, in patients with type 2 diabetes and impaired glucose tolerance (IGT) in whom hyperglycaemia may trigger IL-1β-associated inflammation leading to suppressed insulin secretion and β-cell dysfunction. Methods: This 4-week, parallel-group study randomized 190 patients with type 2 diabetes 2:1, canakinumab versus placebo, into the following treatment arms: metformin monotherapy, metformin+ sulfonylurea, metformin + sulfonylurea + thiazolidinedione or insulin ± metformin. IGT population (n = 54) was randomized 1:1, canakinumab versus placebo. Primary efficacy assessment was change from baseline in insulin secretion rate (ISR) relative to glucose 0-2 h. Results: Mean changes from baseline to week 4 in ISR relative to glucose at 0-2 h or other time points were not statistically significant for canakinumab versus placebo across groups. ISR (relative to glucose)at 0-0.5 h (first-phase insulin secretion) numerically favoured canakinumab versus placebo in insulin-treated patients {difference in mean change from baseline [point estimate (PE)] 3.81 pmol/min/m2/mmol/l; p=0.0525} and in the IGT group (PE 3.92 pmol/min/2/mmol/l; p=0.1729). Mean change from baseline in fasting plasma glucose favoured canakinumab in the type 2 diabetes/metformin group and the IGT group; however, differences were not statistically significant. Mean change from baseline in peak insulin level and insulin AUC 0-4 h were statistically significantly higher in the canakinumab group in IGT patients. Canakinumab was well tolerated and consistent with known safety experience. Conclusions: The trend towards improving ISR relative to glucose 0-0.5 h in patients treated with insulin supports the hypothesis that insulin secretion can be improved by blocking IL-1β.

Original languageEnglish (US)
Pages (from-to)1088-1096
Number of pages9
JournalDiabetes, Obesity and Metabolism
Volume14
Issue number12
DOIs
StatePublished - Dec 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Rissanen, A., Howard, C. P., Botha, J., Thuren, T., Proietto, J., Nicholson, G., Colman, P., Aronson, R., Goldenberg, R., Khandwala, H., Dumas, R., Hallé, J. P., Rissanen, A., Keinanen-Kiukaanniemi, S., Laine, M., Anderten, H., Boeckmann, U., Chevts, J., Keuthage, W., ... Lipetz, R. (2012). Effect of anti-IL-1β antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes: Results of a randomized, placebo-controlled trial. Diabetes, Obesity and Metabolism, 14(12), 1088-1096. https://doi.org/10.1111/j.1463-1326.2012.01637.x