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

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Aims: The 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.

Methods: In a double-blinded, placebo-controlled, randomized, 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 6-week wash-out period. At the end of each period, two randomized 4-h liquid mixed meal tests with concomitant infusion of exendin(9-39)NH2 and saline, respectively, were performed.

Results: Compared 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 ± s.d.) during exendin(9-39)NH2 infusion in the acarbose period vs a 39 ± 27% increase during the placebo period (P = 0.0163).

Conclusions: We 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.

Original languageEnglish
JournalEuropean Journal of Endocrinology
Volume184
Issue number3
Pages (from-to)383-394
Number of pages12
ISSN0804-4643
DOIs
Publication statusPublished - Mar 2021

    Research areas

  • Acarbose/pharmacology, Aged, Aged, 80 and over, Blood Glucose/drug effects, Cross-Over Studies, Denmark, Diabetes Mellitus, Type 2/drug therapy, Double-Blind Method, Female, Gastric Emptying/drug effects, Glucagon-Like Peptide 1/physiology, Humans, Insulin Resistance, Insulin-Secreting Cells/drug effects, Male, Metformin/therapeutic use, Middle Aged, Placebos, Postprandial Period/drug effects

ID: 61868796