In a group of fifty-eight patients with mild maturity onset diabetes, the double oral glucose loading test after StaubTraugott, the intravenous glucose loading test with calculation of the glucose disappearance rates and intraduodenal glucose loading test were performed before and after phenethylbiguanide administration. The drug produced no changes in the intravenous glucose loading test, whereas it caused a significant lowering of the glycemia curves obtained in oral and intraduodenal loading tests. In order to complement these investigations, double fistula of the initial and distal segment of the small intestine were made in six dogs and perfusion of the intestine performed in situ with a glucose solution. Previous administration of butylbiguanide produced a marked flattening of the glycemia curve, and the recovery of glucose from the distal segment of the small intestine was more than doubled.
Suppression of intestinal glucose absorption by biguanide derivatives, demonstrated in the present study, could be explained by specific action of these compounds on the small intestine wall. Biguanide derivatives, accumulated in intestinal cells in higher concentrations than in other tissues, could impair glucose utilization by suppressing the synthesis of ATP required for active absorption of glucose.
