Glucagon-Like Peptide-1 Receptor Agonist Treatment Prevents Glucocorticoid-Induced Glucose Intolerance and Islet-Cell Dysfunction in Humans

  1. Michaela Diamant, MD, PHD1
  1. 1Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
  2. 2Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands
  3. 3The Institute of Clinical Biochemistry and Pathobiochemistry, The German Diabetes Center, Düsseldorf, Germany
  1. Corresponding author: Daniël H. van Raalte, d.vanraalte{at}
  1. D.H.v.R. and R.E.v.G. contributed equally to this work.


OBJECTIVE Glucocorticoids (GCs) are regarded as diabetogenic because they impair insulin sensitivity and islet-cell function. This study assessed whether treatment with the glucagon-like peptide receptor agonist (GLP-1 RA) exenatide (EXE) could prevent GC-induced glucose intolerance.

RESEARCH DESIGN AND METHODS A randomized, placebo-controlled, double-blind, crossover study in eight healthy men (age: 23.5 [20.0–28.3] years; BMI: 26.4 [24.3–28.0] kg/m2) was conducted. Participants received three therapeutic regimens for 2 consecutive days: 1) 80 mg of oral prednisolone (PRED) every day (q.d.) and intravenous (IV) EXE infusion (PRED+EXE); 2) 80 mg of oral PRED q.d. and IV saline infusion (PRED+SAL); and 3) oral placebo-PRED q.d. and intravenous saline infusion (PLB+SAL). On day 1, glucose tolerance was assessed during a meal challenge test. On day 2, participants underwent a clamp procedure to measure insulin secretion and insulin sensitivity.

RESULTS PRED+SAL treatment increased postprandial glucose levels (vs. PLB+SAL, P = 0.012), which was prevented by concomitant EXE (vs. PLB+SAL, P = NS). EXE reduced PRED-induced hyperglucagonemia during the meal challenge (P = 0.018) and decreased gastric emptying (vs. PRED+SAL, P = 0.028; vs. PLB+SAL, P = 0.046). PRED+SAL decreased first-phase glucose- and arginine-stimulated C-peptide secretion (vs. PLB+SAL, P = 0.017 and P = 0.05, respectively), whereas PRED+EXE improved first- and second-phase glucose- and arginine-stimulated C-peptide secretion (vs. PLB+SAL; P = 0.017, 0.012, and 0.093, respectively).

CONCLUSIONS The GLP-1 RA EXE prevented PRED-induced glucose intolerance and islet-cell dysfunction in healthy humans. Incretin-based therapies should be explored as a potential strategy to prevent steroid diabetes.


  • Received August 30, 2010.
  • Accepted October 23, 2010.

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