LBODP038 Metformin-Associated Severe Lactic Acidosis: A Case Study Of The Perfect Storm

BACKGROUND: Metformin carries a rare risk of lactic acidosis. Medications that can increase the concentration of metformin in the serum can increase the risk of lactic acidosis. Similarly, kidney dysfunction leads to decreased clearance of the drug, hence potentiating its adverse effects. CLINICAL CASE: A 62-year-old male with HIV (undetectable viral load) on dolutegravir, atazanavir/cobicistat, rilpivrine, type 2 DM (A1C 7.2%) on metformin and dulaglutide presented with 1 day history of dyspnea. He had a respiratory rate of 28 and heart rate of 131. Blood glucose was 43 mg/dL (nl 74-99 mg/dL). Labs were also notable for lactate 23.6 mmol/L (nl 0.4-2 mmol/L), severe anion gap metabolic acidosis with pH <6.8, bicarbonate 5 mmol/L (nl 21-32 mmol/L). Creatinine was 2.29 mg/dL (nl 0.5-1.3 mg/dL) with a normal baseline kidney function. Beta-hydroxybutyrate was elevated at 0.73 mmol/L (nl 0. 02-0.27 mmol/L). Osmolar gap was 17.3 mOsm, ethanol level was 22 mg/dL (nl <10 mg/dL), ethylene glycol was not detected. Patient reported drinking four beers daily but endorsed binge drinking the previous night with associated emesis. Review of records showed that the patient was started on dulaglutide recently and he endorsed nausea and diarrhea with initiation of the medication. He otherwise had no changes in his metformin dose or antiretroviral regimen. He was admitted to the ICU for further management of his severe lactic acidosis. Patient's antiretroviral regimen, dulaglutide, and metformin were held on admission. Medical toxicology was consulted, and metformin associated lactic acidosis was suspected. He was initiated on dialysis and his lactic acidosis resolved within 24 hours. His antiretroviral regimen was resumed prior to discharge when his creatinine improved to 1.38 mg/dL. Metformin was discontinued and he was discharged on dulaglutide with endocrinology follow up. CONCLUSION: This case demonstrates how multiple factors such as alcohol use, kidney injury, and other medications can increase the, otherwise rare, risk of lactic acidosis in patients taking metformin. The patient had experienced GI losses due to emesis from his increased alcohol intake as well as diarrhea with the initiation of dulaglutide leading to dehydration and acute kidney injury. The latter can give rise to decreased metformin clearance. In addition, dolutegravir increases metformin plasma exposure. Together, the constellation of factors had likely led to increased metformin plasma levels and associated severe lactic acidosis. Patients should be counseled on the use of alcohol while taking metformin. Additionally, drug interactions should be monitored, and dose reductions of metformin should be considered in patients taking dolutegravir. Presentation: No date and time listed