PII-122 - EFFECT OF THE CHOLESTYRAMINE-INDUCED ALTERATION OF BILE ACID POOL IN THE GUT ON THE PHARMACODYNAMICS OF METFORMIN: AN EXPLORATORY STUDY.

D. Yoon¹, J. Kim², J. Cho², S. Yoon², J. Chung²; ¹University of Florida, Gainesville, FL, USA, ²Seoul National University Bundang Hospital, Seoul, Republic of Korea.

Background: The study aimed to evaluate the effect of cholestyramine-induced alteration of bile acid pool in the gut on pharmacodynamics (PDs) of metformin to explore glucose-lowering mechanism of metformin.

Methods: An open-label, two-period one sequence crossover study was conducted with healthy male adults. Each period consisted of both before and after metformin treatments. Cholestyramine was administered during the second period to change the bile acid pool. For, PD assessment, oral glucose tolerance test was conducted at each treatment in both periods (baseline, metformin treatment, cholestyramine treatment, and metformin/cholestyramine treatment). Metformin was administered three times (500 mg, 500 mg, 1000 mg), and cholestyramine 4 g was administered three times per day for 7 days. Maximum serum glucose concentration, area under the glucose concentration curve from (AUGC), and HOMA-IR were calculated. Baseline corrected PD parameters were calculated by subtracting the values before metformin administration from those after metformin administration. Safety was assessed throughout the study.

Results: A total of 14 subjects completed the study. The mean values of three PD parameters were all decreased after metformin administration in both periods. The mean values of baseline corrected parameters decreased after cholestyramine administration. The baselined corrected AUGC was significantly changed (p=0.0384). Diarrhea, the most frequently occurred adverse event in the study, occurred in 10 subjects during metformin treatment (p < 0.001), while 1 subject during cholestyramine and metformin/cholestyramine treatments, respectively.

Conclusion: Cholestyramine affected the glucose-lowering effect and safety of metformin by the possible change in the bile acid pool in the gut.