Key result
Metformin use was significantly associated with a decreased risk of amiodarone-associated interstitial lung disease (adjusted ROR 0.46) in a large pharmacovigilance database analysis.
Why the study?
The study was conducted to examine the association between metformin, as well as other antidiabetic drugs, and amiodarone-induced adverse events using a spontaneous adverse event database.
Does metformin reduce amiodarone-associated extracardiac adverse events in patients receiving amiodarone?
Observational (n=6,153,696)
Does metformin reduce amiodarone-associated extracardiac adverse events in patients receiving amiodarone?
Answers are grounded in this paper and cite their sources.
Metformin is a candidate drug that may reduce the risk of amiodarone-induced hyperthyroidism and interstitial lung disease.
The association between metformin and amiodarone-induced adverse events was examined using spontaneous adverse event database. Additionally, the association between other antidiabetic drugs and amiodarone-induced adverse events were also examined. Methods: A total of 6,153,696 reports from the first quarter of 2004 through the fourth quarter of 2015 were downloaded from the US Food and Drug Administration adverse event reporting system. Reporting odds ratio (ROR) and information component (IC) were used to detect associations between antidiabetic drugs and amiodarone-associated adverse events. Additionally, subset data analysis was performed to investigate whether the use of antidiabetic drugs further increased or decreased the risk of adverse events in patients receiving amiodarone therapy. Next, the RORs were adjusted for coadministered antidiabetic drugs using logistic regression analysis. Results: By whole dataset analysis, significant inverse associations were found between metformin and interstitial lung disease (ROR 0.84, 95% confidence interval [CI] 0.79-0.90; IC -0.24, 95% CI -0.33 to -0.15). In the subset data analysis, metformin (ROR 0.62, 95%CI 0.43-0.89; IC -0.63, 95%CI -1.14 to -0.11), sulfonylureas (ROR 0.53, 95%CI 0.32-0.85; IC -0.85, 95%CI -1.53 to -0.17), and dipeptidyl peptidase-4 (DPP-4) inhibitors (ROR 0.25, 95%CI 0.08-0.78; IC -1.66, 95%CI -3.08 to -0.23) were inversely associated with hyperthyroidism. Additionally, metformin (ROR 0.43, 95%CI 0.33-0.57; IC -1.09, 95%CI -1.49 to -0.69), sulfonylureas (ROR 0.64, 95%CI 0.48-0.86; IC -0.59, 95%CI -1.00 to -0.17), and DPP-4 inhibitors (ROR 0.47, 95%CI 0.27-0.81; IC -0.99, 95%CI -1.76 to -0.22) were inversely associated with interstitial lung disease. In the logistic regression analyses, DPP-4 inhibitors (adjusted ROR 0.32, 95% CI 0.10-1.00) and metformin (adjusted ROR 0.46, 95% CI 0.34-0.62) were inversely associated with amiodarone-associated hyperthyroidism and interstitial lung disease, respectively. Conclusion: Metformin is a candidate drug to reduce the risk of amiodarone-induced hyperthyroidism and interstitial lung disease.
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Kinoshita et al. (2020) conducted an observational in Amiodarone-associated adverse events (n=6,153,696). Metformin vs. Non-use of metformin / other reports was evaluated on Amiodarone-associated interstitial lung disease (adjusted ROR 0.46, 95% CI 0.34-0.62). Metformin use was significantly associated with a decreased risk of amiodarone-associated interstitial lung disease (adjusted ROR 0.46) in a large pharmacovigilance database analysis.
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