Kidney360Sep 4, 2026

Lactic Acidosis and Normal-Blood-Sugar Ketoacidosis Linked to Metformin Triggered by a Diabetes Drug: A Case Report and Review

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 5, 2026

Abstract

Metformin-associated lactic acidosis (MALA) has an incidence of less than 10 per 100,000 patient-years and a mortality rate of 30-50%.

MALA is often linked with acute kidney injury, which affects the body's ability to excrete metformin and increases lactate production.
Euglycemic diabetic ketoacidosis (euDKA) can occur in patients using glucagon-like peptide-1 receptor agonists, alongside sodium-glucose cotransporter-2 inhibitors.
The combination of severe MALA and ketoacidosis with relatively low blood glucose levels is extremely rare and not well-documented.
Gastrointestinal side effects from medications like metformin and GLP-1 receptor agonists may trigger MALA in patients.
Early measurement of serum beta-hydroxybutyrate is crucial for recognizing this condition and initiating timely renal replacement therapy.

Simplified

Metformin-associated lactic acidosis (MALA) is an uncommon but often fatal complication of metformin therapy (incidence less than 10 per 100,000 patient-years; with a 30-50% mortality). MALA most commonly occurs with acute kidney injury, which impairs metformin excretion and inhibits mitochondrial complex I, shifting pyruvate metabolism toward lactate production. Euglycemic diabetic ketoacidosis (euDKA), classically defined as DKA with glucose below 250 mg/dL, is increasingly recognized not only with sodium-glucose cotransporter-2 (SGLT2) inhibitors but also with glucagon-like peptide-1 receptor agonists (GLP-1 RA) through appetite suppression, vomiting, and reduced intake. Concurrent MALA and ketoacidosis with relative euglycemia is exceedingly rare, with no published synthesis of such cases to guide recognition or management. We present a case of severe MALA with ketoacidosis and relative euglycemia in a 59-year-old woman with type 2 diabetes on metformin and tirzepatide, managed successfully with emergent sequential hemodialysis and high-dose continuous venovenous hemodiafiltration. We also review reported MALA cases with GLP-1 RA use to identify shared precipitants, risk factors, and outcomes. The key lesson is that, in patients on metformin and a GLP-1 RA, gastrointestinal side effects can precipitate MALA, while a disproportionately low glucose can mask the accompanying ketoacidosis. Recognizing this pattern demands early measurement of serum beta-hydroxybutyrate and prompt initiation of renal replacement therapy.

Lactic Acidosis and Normal-Blood-Sugar Ketoacidosis Linked to Metformin Triggered by a Diabetes Drug: A Case Report and Review

Abstract

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