A Case of Metformin-Associated Lactic Acidosis

Abstract

Metformin is a US FDA-approved oral anti-hyperglycemic medication used to treat non-insulin-dependent diabetes mellitus (NIDDM). Metformin, a biguanide drug, works by reducing glucose production in the liver, decreasing intestinal absorption, and improving insulin sensitivity, leading to lower blood glucose levels. Metformin is generally considered to be a medication with a good safety profile and high tolerability. However, metformin therapy is associated with an uncommon but potentially serious complication known as metformin-associated lactic acidosis (MALA), which is marked by severe lactic acid accumulation in the bloodstream. This case introduces an elderly female with multiple comorbidities who presented with confusion, malaise, and lethargy. Her laboratory findings revealed acute renal failure, severe metabolic acidosis, and significantly elevated lactic acid levels consistent with sepsis and possibly MALA. Aggressive resuscitation with fluids and sodium bicarbonate was initiated. Antimicrobial drugs were started for urinary tract infections. She subsequently required endotracheal intubation with invasive ventilation, pressor support, and continuous renal replacement therapy. Her condition gradually improved over several days. The patient ultimately recovered, and at the time of discharge, metformin was discontinued, and a sodium-glucose cotransporter-2 (SGLT-2) inhibitor was initiated. This case underscores the relevance of MALA as a potential complication of metformin therapy, particularly in patients with underlying kidney disease or other risk factors. Timely detection and prompt management of MALA can prevent progression to a critical stage and thus avoid potentially fatal outcomes.

View on Metformin: Antidiabetic and Pleiotropic Effects, Pharmacokinetics, Side Effects, and Sex-Related Differences

“…As is known, the protein transporters involved are expressed differently in human tissues and have high genetic polymorphism, generating wide inter-individual variability in metformin pharmacokinetics, explaining the range of dosage and different antidiabetic effectiveness [ 87 , 88 , 90 ]. The detected C max is around 1 µg/mL, and, in general, the optimal plasma concentration should be less than 2 µg/mL, whereas concentrations greater than 5 µg/mL are considered unsafe due to the increased risk of severe adverse effects, such as lactic acidosis [ 87 , 91 , 92 ]. However, several authors reported blood concentrations of up to 80 µg/mL in subjects treated with metformin, showing high variability in the pharmacokinetics of this drug [ 93 ].…”

“…Other side effects commonly reported are headache, dizziness, fatigue, pruritus, and dysgeusia [ 233 , 234 ]. One of the most feared adverse reactions to metformin treatment is lactic acidosis, which is a rare event with an incidence of 1 in 30,000 patients but can lead to fatal outcomes [ 91 , 235 ]. Generally, the observed cases occurred in patients who received high doses and/or had severe hepatic and renal impairment, old age, and alcoholism [ 236 , 237 ].…”

Septic encephalopathy in the elderly – biomarkers of potential clinical utility

“…Patients with lactate concentrations >4 mmol/L, in the absence or presence of hypotension, have a higher in-hospital mortality than patients with intermediate (2–3 and 3–4 mmol/L) or normal lactate concentrations ( Casserly et al, 2015 ). Metabolic acidosis can induce confusion, malaise and lethargy and thereby resemble septic encephalopathy ( Cruz-Flores, 2021 ; Mahmood et al, 2023 ).…”

Hypoglycaemic, Insulin Modulation and Antioxidant Potentials of Ricinus communis L. Extracts in Streptozotocin-Induced Diabetes Male Wistar Rats

“…Metformin does not, however, come without adverse effects. In rare instances, prolonged usage of the medication can result in lactic acidosis and gastrointestinal problems 15 . Finding complementary or alternative therapy is therefore essential to improving the management of diabetes.…”