From the Guidelines
Yes, lactic acidosis from metformin can be fatal, with a mortality rate of approximately 30-50% in severe cases, as reported in a study from 2018 1.
Risk Factors and Prevention
The condition occurs when metformin accumulates in the body, typically due to impaired kidney function, leading to excessive lactic acid production and decreased clearance.
- Risk factors include renal impairment (especially with GFR <30 ml/min), liver disease, heart failure, severe infection, dehydration, excessive alcohol intake, and advanced age.
- Symptoms of MALA include nausea, vomiting, abdominal pain, lethargy, hyperventilation, and in severe cases, hypotension, hypothermia, and cardiac arrhythmias.
Treatment and Management
Treatment involves immediate discontinuation of metformin, supportive care, correction of acid-base disturbances, and in severe cases, hemodialysis to remove metformin from circulation.
- To prevent MALA, metformin should be temporarily discontinued during acute illness, before procedures requiring contrast agents, or when at risk of dehydration.
- Regular monitoring of kidney function is essential for patients on metformin therapy, as emphasized in a study from 2021 1 and another from 2025 1.
Clinical Considerations
It is crucial to weigh the benefits of metformin against the potential risks, especially in patients with risk factors for lactic acidosis.
- The decision to use metformin should be made on a case-by-case basis, considering the individual patient's profile and medical history, as suggested in a study from 2019 1 and another from 2023 1.
- Healthcare providers should be vigilant in monitoring patients on metformin for signs of lactic acidosis and take prompt action if symptoms arise, as recommended in a study from 2016 1 and another from 2018 1.
From the FDA Drug Label
There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. Metformin hydrochloride, the medicine in metformin hydrochloride tablets, can cause a rare, but serious, side effect called lactic acidosis (a build-up of lactic acid in the blood) that can cause death.
Lactic acidosis from metformin can be fatal. The FDA drug label for metformin hydrochloride tablets reports postmarketing cases of metformin-associated lactic acidosis, including fatal cases 2. Similarly, the patient information leaflet for metformin hydrochloride tablets also states that lactic acidosis can cause death 2.
- Key points:
- Lactic acidosis is a rare but serious side effect of metformin.
- It can cause death.
- Patients with certain risk factors, such as kidney problems or liver problems, are more likely to develop lactic acidosis.
From the Research
Lactic Acidosis from Metformin
- Lactic acidosis is a rare but potentially life-threatening complication of metformin use, particularly in patients with renal impairment, liver disease, or heart failure 3, 4, 5, 6, 7.
- The overall mortality of lactic acidosis is approximately 50% 6.
- Certain subsets of patients taking metformin are at greater risk of developing lactic acidosis, including those with chronic nephropathy, sepsis, fever, diarrhea, vomiting, or other conditions that reduce metformin renal clearance 3.
- Lactic acidosis almost always develops because of preventable drug accumulation, and prevention is a key factor in avoiding this complication 3.
- Treatment of lactic acidosis typically involves supportive care, including aggressive interventions such as continuous renal replacement therapy (CRRT) to reverse acidosis and clear metformin metabolites 3, 4, 7.
- Early identification and initiation of extracorporeal treatment are crucial in managing severe metabolic acidosis and improving patient outcomes 4.
Risk Factors and Prevention
- Patients with renal impairment, liver disease, or heart failure are at increased risk of developing lactic acidosis while taking metformin 3, 4, 5, 6, 7.
- Patients should be aware that discontinuation of metformin for a limited time does not affect their health, but it may avoid a serious, potentially fatal adverse event 3.
- Prevention of lactic acidosis involves careful monitoring of patients taking metformin, particularly those with compromised renal function, and prompt discontinuation of the drug in the event of a concomitant disease or situation that reduces metformin renal clearance 3.
Treatment and Management
- Continuous renal replacement therapy (CRRT) plays a crucial role in the treatment of lactic acidosis complicated by acute kidney injury, improving survival by correcting acidosis, electrolyte alterations, and maintaining fluid balance 3.
- Hemodialysis followed by peritoneal dialysis, continuous bicarbonate infusion, and tight glucose control may also be effective in treating lactic acidosis 6.
- Early diagnosis and recognition of the fundamental elements of lactic acidosis are important for its management, and starting hemodialysis early and prolonged treatment can solve complicated clinical status, correct acidosis, and restore kidney function in patients with serious comorbidity 7.