Session: SAT 824-833-GI Regulatory Peptides
Bench to Bedside
Poster Board SAT-832
Methods: In a controlled clinical study, we monitored various metabolic variables and the gut microbiome in 14 T2D patients over the course of four separate visits when metformin was withdrawn and re-instated, using pre-defined changes in fasting blood glucose (FBG) levels to determine when the subjects should be investigated: ( 1) at baseline, 2) 7 days after withdrawing metformin, 3) when mean FBG increased by 25% , and 4) when mean FBG was back to baseline values after restarting metformin.
Results: Bile acids. The total serum bile acid pool increased significantly after the withdrawal of metformin (mainly primary bile acids) (p=0.0004 ). Analysis of concentration indicated that the largest quantitative changes were in AUC (4-8 h) for chenodeoxycholic acid. A circadian rhythm of bile acid secretion was observed. Faecal concentrations of the bile acids (mostly the secondary bile acids, lithocholic and deoxycholic acids) were greater when subjects were on metformin, although the differences were not statistically significant.Incretins. Metformin withdrawal significantly reduced AUC (0-12 h) of total and active GLP-1, with little change in GIP or PYY, indicating that metformin may increase the secretion of GLP-1 and inhibit the degrading enzyme, dipeptidyl peptidase-IV (DPP-IV). Faecal Microbiome analysis. We used 16S rRNA sequencing to identify bacterial species in the gut of each subject at the four timepoints. The total number of microbial species was not significantly influenced by metformin, but Veillonella and Eubacterium increased when off metformin, while Asaccharobacter and Acetanaerobacterium decreased, although these associations were not significant after correction for the total number of species detected in the study. Further analyses are underway investigating microbial gene and pathway level associations.
Conclusion: We have shown that metformin has novel pharmacologies in the gut in T2D, including modulation of bile acid reabsorption from the gut lumen, secretion of gut hormones and alteration of the faecal microbiome. Understanding the potential novel effects of metformin will be important to identify potential novel approaches to control blood glucose and obesity.
Nothing to Disclose: AN, SM, SV, AK, GS, GL, DR, AS, JB, DR, DB, AN, DN
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