EFFECT OF METFORMIN ON BILE-SALT CIRCULATION AND INTESTINAL MOTILITY IN TYPE-2 DIABETES-MELLITUS

Gastrointestinal symptoms can be a limiting factor in optimizing metfo rmin therapy, particularly at the onset of treatment. The underlying c ause remains unclear. We have investigated whether metformin changes o ral-caecal transit and if it causes bile salt malabsorption using the lactulose breath test and orally administered C-14-glycocholate follow ed by breath (CO2)-C-14 measurement over 6 h and stool collection for 72 h, respectively. Twenty-four diet and/or sulphonylurea treated pati ents underwent 7 days of baseline investigations before entering a ran domized double-blind crossover study of 21 days duration with either m etformin (850 mg bd) or placebo. No difference was observed in the ora l-caecal transit time but a change in fasting plasma glucose was obser ved of 2.6 mmol l(-1) (95 % Cl 1.3, 3.8). Significant increases in per centage (CO2)-C-14 breath elimination were observed during treatment w ith metformin (9.7 +/- 6.3) compared with placebo (3.1 +/- 1.9) p = 0. 020. In addition, percentage faecal C-14 bile salt excretion was incre ased with metformin (17.2 +/- 9.9 vs 10.1 +/- 6.9) p = 0.037. A signif icant association (p = 0.002) emerged for stool bile salt content and liquidity of the stool. We conclude that metformin may cause gastroint estinal disturbances by reducing ileal bile salt reabsorption leading to elevated colonic bile salt concentrations. (C) 1998 John Wiley & So ns, Ltd.