Safe Use of Metformin in Mitochondrial Diabetes in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes: Insights From a Patient With m.3243A>G Mutation.

Background/Objective: Diabetes mellitus is often seen in patients with multisystem mitochondrial disorders such as mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Although metformin is the cornerstone of type 2 diabetes pharmacotherapy, its use in MELAS is discouraged owing to concerns of worsening lactic acidosis. The objective of this report is to present a case where metformin use in MELAS was both clinically beneficial and safely tolerated. Case Report: A 49-year-old man, diagnosed with presumed type 2 diabetes at the age of 34 years, was started on metformin and glipizide resulting in good glucose control. Subsequent recognition of MELAS in other family members and the presence of sensorineural hearing loss prompted genetic testing, which confirmed the m.3243A>G mitochondrial sequence variant. Tapering of metformin to avoid potential lactic acidosis resulted in unacceptable hyperglycemia with fasting glucose in the range of 200 to 250 mg/dL. Metformin was then reintroduced, leading to improved glycemic control without elevation in lactate or unmasking of neurologic symptoms. Discussion: Metformin can potentially increase lactic acidosis and neurologic manifestations in patients with mitochondrial disorders as reported previously; however, this is not a universal finding. Metformin can be safely used in select patients with MELAS under appropriate clinical supervision. Withholding metformin in all patients with mitochondrial diabetes is unnecessary and possibly disadvantageous. Conclusion: This case highlights the importance of individualized therapeutic decisions in MELAS. Metformin, with appropriate monitoring, may represent a safe and effective treatment option for glycemic control even in mitochondrial diabetes.