Effect of metformin on bile salt circulation and intestinal motility in Type 2 diabetes mellitus

✍ Scribed by Scarpello, J.H.B.; Hodgson, E.; Howlett, H.C.S.

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 136 KB
• Volume: 15
• Category: Article
• ISSN: 0742-3071
• DOI: 10.1002/(sici)1096-9136(199808)15:8<651::aid-dia628>3.0.co;2-a

✦ Synopsis

Gastrointestinal symptoms can be a limiting factor in optimizing metformin therapy, particularly at the onset of treatment. The underlying cause remains unclear. We have investigated whether metformin changes oral-caecal transit and if it causes bile salt malabsorption using the lactulose breath test and orally administered 14 C-glycocholate followed by breath 14 CO 2 measurement over 6 h and stool collection for 72 h, respectively. Twenty-four diet and/or sulphonylurea treated patients underwent 7 days of baseline investigations before entering a randomized double-blind crossover study of 21 days duration with either metformin (850 mg bd) or placebo. No difference was observed in the oral-caecal transit time but a change in fasting plasma glucose was observed of 2.6 mmol l ؊1 (95 % CI 1.3, 3.8). Significant increases in percentage 14 CO 2 breath elimination were observed during treatment with metformin (9.7 ؎ 6.3) compared with placebo (3.1 ؎ 1.9) p = 0.020. In addition, percentage faecal 14 C bile salt excretion was increased with metformin (17.2 ؎ 9.9 vs 10.1 ؎ 6.9) p = 0.037. A significant association (p = 0.002) emerged for stool bile salt content and liquidity of the stool. We conclude that metformin may cause gastrointestinal disturbances by reducing ileal bile salt reabsorption leading to elevated colonic bile salt concentrations.