Work

Diagnosing Metformin Intoxication with High-Resolution Platelet Respirometry: A Case Report

Year: 2026

Type: article

Abstract: Metformin-associated lactic acidosis (MALA) involves mitochondrial Complex I inhibition, traditionally diagnosed via indirect markers. We present platelet high-resolution respirometry (HRR) as a novel "liquid biopsy" to directly quantify metformin-induced systemic bioenergetic lesions. A 65-year-old diabetic male presented with severe lactic acidosis, acute kidney injury, and profound hypoglycemia after intentionally overdosing on metformin (120 g), dapagliflozin (600 mg), and insulin glargine (300 U). While hemodialysis cleared plasma metformin and resolved the acidosis, refractory hypoglycemia required high-dose IV glucose for over six days. Day 2 platelet HRR revealed severe Complex I inhibition despite significantly decreased plasma metformin, indicating a profound "toxicodynamic lag." Mitochondrial bioenergetics recovered by Day 7, reflecting natural platelet turnover. The protracted hypoglycemia was driven by a synergistic triad: metformin-inhibited gluconeogenesis, insulin glargine's prolonged depot effect, and dapagliflozin-induced persistent renal glucose wasting. Platelet HRR has the potential to be a clinically applicable tool to reveal the "hidden" cellular phase of metformin toxicity missed by standard biomarkers. Furthermore, clinicians must anticipate severe, protracted hypoglycemia in mixed overdoses involving SGLT2 inhibitors.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27104631

Authors: Ondřej Sobotka, Pavla Staňková, Joao Fortunato, Eva Trčková, Pavel Skořepa

Institutions: Charles University, University Hospital Hradec Králové, University of Defence

Language: English

Topic: Poisoning and overdose treatments

Subfield: Emergency Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499