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

in European Journal of Endocrinology
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  • 1 Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
  • 2 Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • 3 Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • 4 Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • 5 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • 6 Steno Diabetes Center Copenhagen, Gentofte, Denmark

Correspondence should be addressed to F K Knop; Email: filip.krag.knop.01@regionh.dk
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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.

Supplementary Materials

    • Supplementary figure 1. Ad libitum food intake
    • Supplementary figure 2. Appetite and satiety measures
    • Supplementary figure 3. CCK and gallbladder volume
    • Supplementary figure 4. Gastrin

 

     European Society of Endocrinology

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