Metformin and risk of hepatocellular carcinoma in patients with type 2 diabetes
Journal
Liver International
Journal Volume
38
Journal Issue
11
Pages
2018-2027
Date Issued
2018
Author(s)
Abstract
Background: Whether metformin may reduce hepatocellular carcinoma (HCC) risk requires confirmation. Methods: Type 2 diabetes patients newly diagnosed during 1999-2005 and with 2 or more prescriptions of antidiabetic drugs were enrolled from the Taiwan’s National Health Insurance database. A total of 173?917 ever-users and 21?900 never-users of metformin were identified (unmatched cohort). A 1:1 matched-pair cohort of 21?900 ever-users and 21?900 never-users based on a propensity score (PS) was created. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using the PS. In addition, interactions with aspirin and statin were evaluated. Results: In the unmatched cohort, 619 never-users and 2642 ever-users developed HCC, with a respective incidence of 668.0 and 330.7 per 100?000 person-years and an overall hazard ratio of 0.49 (95% confidence interval: 0.45-0.54). The hazard ratios for the first (<25.7?months), second (25.7-56.9?months) and third (>56.9?months) tertile of cumulative duration of metformin therapy were 0.89 (0.81-0.98), 0.50 (0.46-0.56) and 0.23 (0.21-0.26) respectively. Analyses of the matched cohort showed an overall hazard ratio of 0.76 (0.67-0.85), and the hazard ratios for the respective tertiles were 1.39 (1.19-1.62), 0.77 (0.65-0.91) and 0.37 (0.30-0.45). Aspirin and statin were observed to have a significant interaction with metformin. Conclusions: Metformin was associated with a reduced risk of HCC in a dose-response pattern. Users of both metformin and aspirin or metformin and statin had the lowest risk. ? 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Subjects
diabetes mellitus; hepatocellular carcinoma; metformin; Taiwan
SDGs
Other Subjects
acarbose; acetylsalicylic acid; hydroxymethylglutaryl coenzyme A reductase inhibitor; insulin; meglitinide; metformin; pioglitazone; rosiglitazone; sulfonylurea; acetylsalicylic acid; antidiabetic agent; hydroxymethylglutaryl coenzyme A reductase inhibitor; metformin; adult; Article; cancer risk; controlled study; diabetic patient; female; human; insulin dependent diabetes mellitus; liver cell carcinoma; major clinical study; male; middle aged; non insulin dependent diabetes mellitus; prescription; risk reduction; aged; cohort analysis; complication; factual database; incidence; liver cell carcinoma; liver tumor; non insulin dependent diabetes mellitus; propensity score; proportional hazards model; risk factor; Taiwan; Aged; Aspirin; Carcinoma, Hepatocellular; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 2; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Incidence; Liver Neoplasms; Male; Metformin; Middle Aged; Propensity Score; Proportional Hazards Models; Risk Factors; Risk Reduction Behavior; Taiwan
Publisher
Blackwell Publishing Ltd
Type
journal article