Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes
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Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes. / Brønden, Andreas; Albér, Anders; Rohde, Ulrich; Rehfeld, Jens F; Holst, Jens J; Vilsbøll, Tina; Knop, Filip K.
In: The Journal of clinical endocrinology and metabolism, Vol. 102, No. 11, 11.2017, p. 4153-4162.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes
AU - Brønden, Andreas
AU - Albér, Anders
AU - Rohde, Ulrich
AU - Rehfeld, Jens F
AU - Holst, Jens J
AU - Vilsbøll, Tina
AU - Knop, Filip K
PY - 2017/11
Y1 - 2017/11
N2 - Context: Despite a position as the first-line pharmacotherapy in type 2 diabetes, the glucose-lowering mechanisms of metformin remain to be fully clarified. Gut-derived modes of action, including suppression of bile acid reabsorption and a resulting increase in glucagon-like peptide-1 (GLP-1) secretion, have been proposed.Objective: The aim of this study was to assess the GLP-1 secretory and glucometabolic effects of endogenously released bile, with and without concomitant single-dose administration of metformin in patients with type 2 diabetes.Design: Randomized, placebo-controlled, and double-blinded crossover study.Setting: This study was conducted at Center for Diabetes Research, Gentofte Hospital, Denmark.Patients: Fifteen metformin-treated patients with type 2 diabetes; all participants completed the study.Interventions: Four experimental study days in randomized order with administration of either 1500 mg metformin or placebo in combination with intravenous infusion of cholecystokinin (0.4 pmol × kg-1 × min-1) or saline.Main Outcome Measure: Plasma GLP-1 excursions as measured by baseline-subtracted area under the curve.Results: Single-dose metformin further enhanced bile acid-mediated induction of GLP-1 secretion (P = 0.02), whereas metformin alone did not increase plasma GLP-1 concentrations compared with placebo (P = 0.17). Metformin, both with (P = 0.02) and without (P = 0.02) concomitant cholecystokinin-induced gallbladder emptying, elicited reduced plasma glucose excursions compared with placebo. No GLP-1-mediated induction of insulin secretion or suppression of glucagon was observed.Conclusions: Metformin elicited an enhancement of the GLP-1 response to cholecystokinin-induced gallbladder emptying in patients with type 2 diabetes, whereas no derived effects on insulin or glucagon secretion were evident in this acute setting.
AB - Context: Despite a position as the first-line pharmacotherapy in type 2 diabetes, the glucose-lowering mechanisms of metformin remain to be fully clarified. Gut-derived modes of action, including suppression of bile acid reabsorption and a resulting increase in glucagon-like peptide-1 (GLP-1) secretion, have been proposed.Objective: The aim of this study was to assess the GLP-1 secretory and glucometabolic effects of endogenously released bile, with and without concomitant single-dose administration of metformin in patients with type 2 diabetes.Design: Randomized, placebo-controlled, and double-blinded crossover study.Setting: This study was conducted at Center for Diabetes Research, Gentofte Hospital, Denmark.Patients: Fifteen metformin-treated patients with type 2 diabetes; all participants completed the study.Interventions: Four experimental study days in randomized order with administration of either 1500 mg metformin or placebo in combination with intravenous infusion of cholecystokinin (0.4 pmol × kg-1 × min-1) or saline.Main Outcome Measure: Plasma GLP-1 excursions as measured by baseline-subtracted area under the curve.Results: Single-dose metformin further enhanced bile acid-mediated induction of GLP-1 secretion (P = 0.02), whereas metformin alone did not increase plasma GLP-1 concentrations compared with placebo (P = 0.17). Metformin, both with (P = 0.02) and without (P = 0.02) concomitant cholecystokinin-induced gallbladder emptying, elicited reduced plasma glucose excursions compared with placebo. No GLP-1-mediated induction of insulin secretion or suppression of glucagon was observed.Conclusions: Metformin elicited an enhancement of the GLP-1 response to cholecystokinin-induced gallbladder emptying in patients with type 2 diabetes, whereas no derived effects on insulin or glucagon secretion were evident in this acute setting.
KW - Journal Article
U2 - 10.1210/jc.2017-01091
DO - 10.1210/jc.2017-01091
M3 - Journal article
C2 - 28938439
VL - 102
SP - 4153
EP - 4162
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 11
ER -
ID: 185871674