After ingestion of metformin, a drug of the biguanide class, there are gastrointestinal side effects in the form of nausea and vomiting, and about 30% of the drug is recovered in feces. The purpose of this work was to explain these two phenomena. Two sets of experiments were carried out.

Study 1 evaluated the gastroduodenal (GD) absorption in six healthy volunteers by means of an intubation method, employing a twin-lumen tube introduced into the intestine and another into the stomach. Metformin 1 g was introduced into the stomach with a homogenized meal containing a non-absorbable marker, ¹⁴C-PEG 4000; another marker, PEG 4000, was perfused continuously into the duodenum at the ampulla of Vater. Samples of GD contents were collected every 15 min during 4 h. Metformin was poorly absorbed from the stomach, about 10% over a 4-h period. It did not modify the gastric emptying of a meal but induced a duodeno-gastric reflux in five out of six subjects. About 20% of the amount of drug emptied from the stomach were absorbed from the duodenum. The delivery process was the rate-limiting factor for metformin absorption from the duodenum. The AUC/24 h increased as the absorption rate from the duodenum increased.

Study 2 investigated in six healthy volunteers, using another intestinal perfusion technique, the jejunal and ileal absorption of metformin. Metformin 400 mg in saline solution was perfused, over a 2-h period, below an inflated balloon, directly into either the jejunum or the ileum. The mean amount of drug absorbed along a 25-cm segment was low, and similar from the jejunum and ileum: 10.8% and 8.8% respectively. When the drug was perfused into the jejunum, the AUC values were about 2.5 times higher than the values when the drug was perfused into the ileum. These results suggest that the whole intestine is necessary for a sufficient absorption of the drug.