Metformin intoxication: clinical characteristics, treatment and prognosis

OBJECTIVES: To identify potential severity predictive factors in patients with metformin intoxication (MI), defined as the need for renal replacement therapy (RRT) and/or patient death. METHODS: Retrospective observational study of patients who presented to the Emergency Department of Hospital del Mar in Barcelona and were diagnosed of MI between January 2010 and April 2024. Data were collected through medical record review. RESULTS: Seventy-two patients were included (43.1% men and 56.9% women), with an average age of 74.8 ± 10.9 years. We defined the primary end point as need for RRT and/or patient death. Fifty patients (69.4%) met the criteria for the primary end point, 39 needed RRT (54.2%) and 21 patients died (28%). Patients who met the primary end point had higher levels of creatinine (7.0 ± 3.2 vs 5.1 ± 3.6 mg/dl, p = 0.03, lactate (14.1 ± 7.3 vs 7.4 ± 4.1 mmol/l, p < 0.001) and gap anion (37.1 ± 11.5 vs 30.4 ± 9.8, p = 0.002), and lower levels of pH (7.02 ± 0.22 vs 7.17 ± 0.15, p = 0.005) and bicarbonate (8.8 ± 5.4 vs 12.7 ± 5.3, p = 0.005) at diagnosis. Metformin levels were determined in 52 patients (72.2%), being higher in patients who met the primary end point (20.1 [12.7-44.3] vs 8.4 [3.8-22.4] µg/mL, p = 0.05). Multivariate analysis identified that lactate levels at admission was the only predictive factor for the primary end point, with an area under the ROC curve of 0.78. The cut-off point for lactate as a predictor for the primary end point was established at ≥9.6 nmol/l, p = 0.01. Also, multivariate analysis identified that metformin levels at admission were a predictive factor for the need for RRT, with an area under the ROC curve of 0.75 and a cut-off point for metformin levels of ≥9.4 µg/mL, p = 0.002. CONCLUSIONS: MI is a severe intoxication, with high mortality and need for RRT. In our study, the only predictive factor for the need of RRT and/or patient death was the level of lactate. Metformin levels at admission were related with the need for RRT.