Adverse event notifications implicating metformin with lactic acidosis in Australia

Abstract

Objective: To summarise the reported lactic acidosis cases associated with metformin from the Australian Therapeutic Goods Administration (TGA) and estimate the incidence of metformin-associated lactic acidosis (MALA) in Australia.

Method: All "lactic acidosis" cases associated with metformin and reported to the TGA between January 1971 and October 2014 were included. Data extracted included patient demographics, medical history and co-existing conditions, metformin dosage and relevant pathology results.

Result: A total of 152 cases of suspected MALA were included in this study. For 20 patients the outcome was unknown. There were 23 patients (n=132, 17.4%) reported as deceased. Plasma lactate levels were higher in non-survivors (p=0.02). Thirty-five patients (n=132, 26.5%) were reported to have at least one pre-existing contraindication to the use of metformin; this proportion was not different between patients who died or survived. Renal impairment was the most common contraindication. Approximately 75% of patients were reported to have at least one clinical condition which might cause acidosis. Metformin dosage, plasma lactate and serum creatinine were not correlated. Based on the cases reported to the TGA, the incidence of MALA in Australia was estimated to be 2.3 (95% CI, 1.5-3.1) cases per 100,000 patient-years between 1997 and 2011.

Conclusion: Pre-existing clinical conditions, such as renal impairment, and acute illnesses associated with lactic acidosis were frequently reported in the cases of MALA. The estimated incidence of MALA was lower than in most previous studies in other countries, probably due to the nature of spontaneous reports to the TGA.

Keywords: Adverse effect; Diabetes; Lactic acidosis; Metformin; Pharmacovigilance.