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Linda Faxius

Biomedical analyst

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

Author

  • Jukka P. Koffert
  • Kirsi Mikkola
  • Kirsi A. Virtanen
  • Anna Maria D. Andersson
  • Linda Faxius
  • Kirsti Hällsten
  • Mikael Heglind
  • Letizia Guiducci
  • Tam Pham
  • Johanna M.U. Silvola
  • Jenni Virta
  • Lars-Olof Eriksson
  • Saila P. Kauhanen
  • Antti Saraste
  • Sven Enerbäck
  • Patricia Iozzo
  • Riitta Parkkola
  • Maria F. Gomez
  • Pirjo Nuutila

Summary, in English

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

Department/s

  • Diabetes and Celiac Unit
  • Diabetic Complications
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2017-09-01

Language

English

Pages

208-216

Publication/Series

Diabetes Research and Clinical Practice

Volume

131

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Keywords

  • Glucose uptake
  • Intestine
  • Metformin

Status

Published

Research group

  • Diabetes and Celiac Unit
  • Diabetic Complications

ISBN/ISSN/Other

  • ISSN: 0168-8227