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

• Published in: European journal of endocrinology Vol. 184; no. 3; pp. 383 - 394
• Main Authors: Dalsgaard, Niels B, Gasbjerg, Lærke S, Hansen, Laura S, Hansen, Nina L, Stensen, Signe, Hartmann, Bolette, Rehfeld, Jens F, Holst, Jens J, Vilsbøll, Tina, Knop, Filip K
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.03.2021; Oxford University Press
• Subjects: Acarbose; Acarbose - pharmacology; Acarbose - therapeutic use; Aged; Aged, 80 and over; Blood Glucose - drug effects; Blood Glucose - metabolism; Carbohydrates; Clinical Study; Cross-Over Studies; Denmark; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Double-Blind Method; Female; Gastric Emptying - drug effects; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - physiology; Glucose; Glucose metabolism; Glucose tolerance; Humans; Insulin Resistance; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Intestine; Male; Metformin; Metformin - therapeutic use; Middle Aged; Placebos; Postprandial Period - drug effects; Secretion; α-Glucosidase; Denmark
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/EJE-20-1121

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.