The role of GLP-1 in the postprandial effects of acarbose in type 2 diabetes.

Abstract

AIMS\nThe alpha-glucosidase inhibitor acarbose is believed to reduce plasma glucose by delaying hydrolysis of carbohydrates. Acarbose-induced transfer of carbohydrates to the distal parts of the intestine increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes.\n\n\nMETHODS\nIn a double-blinded, placebo-controlled, randomised, crossover study, 15 participants with metformin-treated type 2 diabetes (Age 57-85 years, HbA1c 40-74 mmol/mol) were subjected to two 14-day treatment periods with acarbose or placebo, respectively, separated by a six-week wash-out period. At the end of each period, two randomised 4-hour liquid mixed meal tests with concomitant infusion of exendin(9-39)NH2 and saline, respectively, were performed.\n\n\nRESULTS\nCompared to placebo, acarbose increased postprandial GLP-1 concentrations and decreased postprandial glucose. We observed no absolute difference in the exendin(9-39)NH2-induced increase in postprandial glucose excursions between placebo and acarbose periods, but relatively, postprandial glucose was increased by 119 ± 116% (mean ± SD) during exendin(9-39)NH2 infusion in the acarbose period vs. a 39 ± 27% increase during the placebo period (p = 0.0163).\n\n\nCONCLUSIONS\nWe confirm that acarbose treatment stimulates postprandial GLP-1 secretion in patients with type 2 diabetes. Using exendin(9-39)NH2, we did not see an impact of acarbose-induced GLP-1 secretion on absolute measures of postprandial glucose tolerance, but relatively, the effect of exendin(9-39)NH2 was most pronounced during acarbose treatment.