The safety and pharmacokinetics of metformin in patients with chronic liver disease
Abstract
BACKGROUND: The FDA approved 'label' for metformin lists hepatic insufficiency as a risk for lactic acidosis. Little evidence supports this warning.
AIMS: To investigate the safety and pharmacokinetics of metformin in patients with chronic liver disease (CLD).
METHODS: Chronic liver disease patients with and without type 2 diabetes mellitus (T2DM) were studied by a cross-sectional survey of patients already prescribed metformin (n = 34), and by a prospective study where metformin (500 mg, immediate release, twice daily) for up to 6 weeks was prescribed (n = 24). Plasma metformin and lactate concentrations were monitored. Individual pharmacokinetics were obtained and compared to previously published values from healthy and T2DM populations without CLD.
RESULTS: All plasma metformin and lactate concentrations remained below the putative safety thresholds (metformin, 5 mg/L; lactate, 5 mmol/L). Lactate concentrations were unrelated to average steady-state metformin concentrations. In patients with CLD, T2DM was associated with higher plasma lactate concentrations (48% higher than those without T2DM, P < 0.0001). CLD patients with cirrhosis had 23% higher lactate concentrations than those without cirrhosis (P = 0.01). The pharmacokinetics of metformin in CLD patients were similar to patients with T2DM and no liver disease. The ratio of apparent metformin clearance (CLMet /F) to creatinine clearance was marginally lower in CLD patients compared to healthy subjects (median,…
How strong is the evidence?
Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 34 participants or records.
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