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Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes: Results from a randomized clinical trial

Journal article
Authors J. P. Koffert
K. Mikkola
K. A. Virtanen
A. M. D. Andersson
L. Faxius
K. Hällsten
Mikael Heglind
L. Guiducci
T. Pham
J. M. U. Silvola
J. Virta
O. Eriksson
S. P. Kauhanen
A. Saraste
Sven Enerbäck
P. Iozzo
R. Parkkola
M. F. Gomez
P. Nuutila
Published in Diabetes Research and Clinical Practice
Volume 131
Pages 208-216
ISSN 0168-8227
Publication year 2017
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Pages 208-216
Language en
Links doi.org/10.1016/j.diabres.2017.07.0...
Keywords Glucose uptake, Intestine, Metformin
Subject categories Endocrinology and Diabetes

Abstract

Aims Metformin therapy is associated with diffuse intestinal 18F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats. Methods Forty-one patients with newly diagnosed type 2 diabetes were randomized to metformin (1 g, b.i.d), rosiglitazone (4 mg, b.i.d), or placebo in a 26-week double-blind trial. Tissue specific intestinal glucose uptake was measured before and after the treatment period using FDG-PET during euglycemic hyperinsulinemia. In addition, rats were treated with metformin or vehicle for 12 weeks, and intestinal FDG uptake was measured in vivo and with autoradiography. Results Glucose uptake increased 2-fold in the small intestine and 3-fold in the colon for the metformin group and associated with improved glycemic control. Rosiglitazone increased only slightly intestinal glucose uptake. In rodents, metformin treatment enhanced intestinal FDG retention (P = 0.002), which was localized in the mucosal enterocytes of the small intestine. Conclusions Metformin treatment significantly enhances intestinal glucose uptake from the circulation of patients with type 2 diabetes. This intestine-specific effect is associated with improved glycemic control and localized to mucosal layer. These human findings demonstrate directs effect of metformin on intestinal metabolism and elucidate the actions of metformin. Clinical trial number NCT02526615 © 2017 The Authors

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