CT-008 - EFFICACY AND SAFETY OF METFORMIN IN TYPE 2 DIABETIC PATIENTS WITH MILD HEPATIC IMPAIRMENTS: A RETROSPECTIVE COHORT STUDY USING PROPENSITY SCORE MATCHING METHOD.

S. Baek, J. Chung, S. Yoon; Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Republic of Korea.

Background: Metformin is widely used as the first-line oral antidiabetic medication. Although the major mechanism of action is known to be the inhibition of hepatic glucose production, the guidelines for metformin use in patients with mild hepatic impairments are not clearly defined. Our objective was to assess the efficacy and safety of metformin in type 2 diabetic patients with mild hepatic impairments compared to those with normal hepatic function.

Methods: We conducted a retrospective cohort study at a single center using Common Data Model (CDM) data from 2003 to 2020. This study included adults who were prescribed metformin for at least 3 months without any other antidiabetic drugs and had normal baseline renal function. Two cohorts were formed based on the degree of hepatic impairment, using the National Cancer Institute-Organ Dysfunction Working Group criteria: a mild hepatic impairment [Target] group showing laboratory findings of Aspartate transaminase ≥ 40 or Alanine transferase ≥ 40 or Total bilirubin ≥ 1.2 and a normal hepatic function [Control] group. The compounding effect caused by various covariates was corrected using the Propensity-score matching (PSM) method. The primary efficacy measure was the percentage change in HbA1C fraction (%) from baseline, while the rate of adverse events related to metformin was assessed for safety. The Wilcoxon rank sum test and Chi-square test were used to compare the outcomes of the two groups.

Results: Among a total of 2,853 patients (1,247 in the Target and 1,606 in the Control group), 1,550 patients (775 in each group) were included after PSM. The mean percent change in HbA1C fraction (%) was slightly larger in the Target group (-7.072%; 95% CI -7.837– -6.309) compared to the Control group (-5.950%; 95% CI -6.601– -5.299) (P = 0.0028). The incidence rate of adverse events such as abdominal pain and diarrhea showed no statistical difference between the two groups (Chi-square = 0.6982, P = 0.4043).

Conclusion: Clinically, the efficacy and safety of metformin in patients with mild hepatic impairment do not significantly differ from those in patients with normal hepatic function. Hence, unless there are other problems (such as kidney dysfunction), it is not necessary to avoid using metformin in type 2 diabetic patients with mild hepatic impairments.