Treatment with Anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: a randomized, double-blind, placebo-controlled study

J Clin Endocrinol Metab. 2011 Jul;96(7):2119-26. doi: 10.1210/jc.2010-2992. Epub 2011 Apr 20.


Context: Obesity induces low-grade inflammation that may promote the development of insulin resistance. IL-1 is one of the key inflammatory factors.

Objective: The objective of the study was to demonstrate improvement of insulin sensitivity by blocking IL-1.

Design: This was a randomized, double-blind, crossover study.

Setting: The study was based on ambulatory care.

Participants: Participants included nondiabetic, obese subjects with the metabolic syndrome.

Intervention: Intervention included 150 mg anakinra sc once daily or matching placebo for 4 wk.

Main outcome measure: Insulin sensitivity as measured by euglycemic hyperinsulinemic clamp.

Results: A total of 13 of 19 subjects completed the study. Although anakinra treatment resulted in a significantly lower level of inflammation illustrated by a reduction in circulating C-reactive protein concentrations and leukocyte numbers, insulin sensitivity was not significantly different after anakinra treatment (2.8 × 10(-2) ± 0.5 × 10(-2)) compared with placebo treatment (2.4 × 10(-2) ± 0.3 × 10(-2) μmol/kg(-1) · min(-1) · pmol(-1), P = 0.15). Adipose tissue examination, performed to analyze local effects of IL-1 receptor antagonist, showed an increased influx of macrophages after treatment with anakinra most likely due to an injection site reaction caused by the vehicle (0.28 ± 0.05 vs. 0.11 ± 0.01 macrophages per adipocyte, P = 0.005). The differences in individual subject insulin sensitivity after anakinra as compared with placebo between subjects were negatively correlated with macrophage infiltration into the adipose tissue (r(2) = 0.46, P = 0.01). The disposition index increased significantly after anakinra treatment (P = 0.04), reflecting an improvement in β-cell function.

Conclusions: Our results suggest that anakinra does not improve insulin sensitivity in obese, insulin-resistant, nondiabetic subjects.

Trial registration: NCT00928876.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Adipose Tissue / physiopathology
  • Blood Glucose / metabolism*
  • C-Reactive Protein / metabolism
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Glucose Clamp Technique
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance / physiology*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Interleukin 1 Receptor Antagonist Protein / pharmacology
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Male
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / physiopathology
  • Middle Aged
  • Treatment Outcome


  • Blood Glucose
  • Hypoglycemic Agents
  • Interleukin 1 Receptor Antagonist Protein
  • C-Reactive Protein

Associated data