Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes: Results from a randomized clinical trial. (September 2017)

• Record Type: Journal Article
• Authors: Koffert, Jukka P.; Mikkola, Kirsi; Virtanen, Kirsi A.; Andersson, Anna-Maria D.; Faxius, Linda; Hällsten, Kirsti; Heglind, Mikael; Guiducci, Letizia; Pham, Tam; Silvola, Johanna M.U.; Virta, Jenni; Eriksson, Olof; Kauhanen, Saila P.; Saraste, Antti; Enerbäck, Sven; Iozzo, Patricia; Parkkola, Riitta; Gomez, Maria F.; Nuutila, Pirjo
• Is Part Of: Diabetes research and clinical practice. Volume 131(2017)
• Page Start: 208
• Page End: 216
• Publication Date: 2017-09
• Subjects: Intestine -- Glucose uptake -- Metformin; Diabetes -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462
• DOI: 10.1016/j.diabres.2017.07.015
• Languages: English
• ISSNs: 0168-8227

Abstract

Highlights: Metformin treatment increases glucose uptake several fold from the circulation. Metformin induced glucose uptake is localized in the enterocyte layer of the intestine. Metformin's intestine-specific effect is associated with improved glycemic control. Abstract: Aims: Metformin therapy is associated with diffuse intestinal 18 F-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 numberNCT02526615