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Diabetes Obes Metab. 2018 Oct 28. doi: 10.1111/dom.13567. [Epub ahead of print]

Comparative effects of proximal and distal small intestinal administration of metformin on plasma glucose and glucagon-like peptide-1, and gastric emptying after oral glucose, in type 2 diabetes.

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Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China.
Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.



The gastrointestinal tract, particularly the lower gut, may be key to the anti-diabetic action of metformin. We evaluated whether administration of metformin into the distal, vs the proximal, small intestine would be more effective in lowering plasma glucose by stimulating glucagon-like pepetide-1 (GLP-1) and/or slowing gastric emptying (GE) in type 2 diabetes (T2DM).


Ten diet-controlled T2DM patients were studied on three occasions. A transnasal catheter was positioned with proximal and distal infusion ports located 13 and 190 cm beyond the pylorus, respectively. Participants received infusions of (a) proximal + distal saline (control), (b) proximal metformin (1000 mg) + distal saline or (c) proximal saline + distal metformin (1000 mg) over 5 minutes, followed 60 minutes later by a glucose drink containing 50 g glucose and 150 mg 13 C-acetate. "Arterialized" venous blood and breath samples were collected over 3 hours for measurements of plasma glucose, GLP-1, insulin and glucagon, and GE, respectively.


Compared with control, both proximal and distal metformin reduced plasma glucose and augmented GLP-1 responses to oral glucose comparably (P < 0.05 each), without affecting plasma insulin or glucagon. GE was slower after proximal metformin than after control (P < 0.05) and tended to be slower after distal metformin, without any difference between proximal and distal metformin.


In diet-controlled T2DM patients, glucose-lowering via a single dose of metformin administered to the upper and lower gut was comparable and was associated with stimulation of GLP-1 and slowing of GE. These observations suggest that the site of gastrointestinal administration is not critical to the glucose-lowering capacity of metformin.


gastric emptying; glucagon-like peptide-1; metformin; post-prandial blood glucose; small intestinal infusion; type 2 diabetes


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