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Impact of the timing of metformin administration on glycaemic and glucagon-like peptide-1 responses to intraduodenal glucose infusion in type 2 diabetes: a double-blind, randomised, placebo-controlled, crossover study – published online 01/04/2024

Xie graphical abstract

Cong Xie, Peter Iroga, Michelle J. Bound, Jacqueline Grivell, Weikun Huang, Karen L. Jones, Michael Horowitz, Christopher K. Rayner, Tongzhi Wu

Metformin is the first-line drug for the management of type 2 diabetes and has been shown to lower postprandial blood glucose levels via several gastrointestinal mechanisms, including the stimulation of the incretin hormone glucagon-like peptide-1 (GLP-1). In practice, it is recommended that metformin is ingested with meals to minimise potential gastrointestinal adverse effects. However, this may compromise its glucose-lowering efficacy. In this issue, Xie et al ( compare the effects of administering metformin at different time intervals before an enteral glucose load on subsequent blood glucose, insulin and GLP-1 responses in a group of participants with type 2 diabetes who were treated by, and tolerant to, metformin. The study had a double-blind, randomised, placebo-controlled crossover design and the authors used a naso-duodenal catheter to ensure the precise delivery of metformin and the glucose load into the small intestine. The authors found that metformin is more effective at lowering blood glucose and augmenting GLP-1 secretion when given 30–60 min before enteral glucose. The authors conclude that, in metformin-tolerant individuals with type 2 diabetes, administration of metformin before meals may enhance its efficacy for postprandial glycaemic control.

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