Comprehensive analysis of metformin-associated lactic acidosis: Insights from the FDA Adverse Event Reporting System (FAERS)

The present study aims to evaluate metformin-associated lactic acidosis (MALA) using real-world data from the Food and Drug Administration Adverse Event Reporting System (FAERS), providing reference for rational metformin use in clinical practice. Relevant adverse event data from January 2018 to March 2024 was extracted from the FAERS database. Disproportionality analysis, logistic regression, and time-to-event analysis were performed to assess risk factors, temporal patterns, and potential drug interactions associated with MALA. Among 40,883 metformin-related adverse event reports, 10,370 were MALA cases. Diabetes (adjusted odds ratio [OR]: 2.35, 95% confidence interval [CI]: 2.03-2.74), heart disease (adjusted OR: 1.75, 95% CI: 1.44-2.14), and hypertension (adjusted OR: 1.40, 95% CI: 1.21-1.62) were identified as significant risk factors. Contrast media showed the highest signal strength for drug interactions (reporting odds ratio = 323.7, 95% CI: 226.8-461.99), followed by furosemide and bisoprolol. The median time to lactic acidosis onset was 106 days, significantly longer than the 20 days for other adverse events (P < .0001), with 44.0% occurring within 30 days and 40.4% after 360 days of therapy initiation. Taken together, our comprehensive analysis of the FAERS database enhances understanding of MALA risk factors and temporal patterns, contributing to informed decision-making in metformin's clinical application and facilitating timely management of this potentially life-threatening complication, particularly in patients with cardiovascular comorbidities.