Metformin and Liver Disease: How to Prevent Lactic Acidosis

Metformin is the most commonly prescribed drug for type 2 diabetes worldwide. But for people with liver disease, it comes with a warning: risk of lactic acidosis. This isn’t just a theoretical concern-it’s a real, life-threatening condition that can develop quietly and progress fast. Yet, the truth is more complicated than the old warnings suggest. Many patients with mild liver problems can safely take metformin. Others absolutely cannot. The key isn’t just avoiding the drug-it’s knowing when and how to use it safely.

What Is Lactic Acidosis, and Why Does Metformin Cause It?

Lactic acidosis happens when lactate builds up in your blood faster than your body can clear it. Normal lactate levels are below 2 mmol/L. When they hit 5 mmol/L or higher, and your blood pH drops below 7.35, you’re in danger. Symptoms? Nausea, vomiting, stomach pain, weakness, and rapid breathing. In severe cases, you can go into shock or need a ventilator.

Metformin doesn’t create lactate. It interferes with how your body uses it. The drug blocks mitochondrial complex I, a key part of energy production. This forces your cells to rely more on anaerobic metabolism, which produces lactate as a byproduct. Normally, your liver clears that lactate. But if your liver is damaged, it can’t keep up. That’s the problem.

The risk is low-only 3 to 10 cases per 100,000 people per year. But when it happens, it’s serious. About 28% to 47% of patients with severe lactic acidosis die. That’s why doctors have been cautious.

Why Was Metformin Banned in Liver Disease?

Back in the 1990s, metformin was linked to lactic acidosis because its older cousin, phenformin, had killed people. Phenformin was pulled from the market in 1977 after causing hundreds of deaths. Metformin was seen as safer, but regulators didn’t want to take chances. So in 1998, Medsafe and other agencies declared metformin contraindicated in all chronic liver disease.

That rule stuck for decades. But here’s the problem: it wasn’t based on solid evidence. Most of the warnings came from case reports-single patients with multiple risk factors: alcohol abuse, kidney failure, infection, or overdose. Not from studies of people with stable fatty liver or compensated cirrhosis.

Fast forward to 2024. A major case report in Cureus reviewed decades of data and found almost no evidence that metformin causes lactic acidosis in patients with non-alcoholic fatty liver disease (NAFLD). In fact, some studies suggest metformin might actually help NAFLD by reducing liver fat and inflammation.

Who Should NOT Take Metformin?

There are clear red flags. If you have any of these, avoid metformin:

• Decompensated cirrhosis (Child-Pugh Class B or C)
• Acute liver failure
• Severe alcohol-related liver damage with active drinking
• Shock, sepsis, or acute heart failure
• Severe kidney impairment (eGFR below 30 mL/min/1.73m²)

These conditions mean your liver can’t clear lactate, and your kidneys can’t flush out metformin. Together, that’s a perfect storm.

The 2022 Veterans Affairs study found only 8.3% of patients with Child-Pugh Class B cirrhosis were on metformin. That’s not because doctors are overcautious-it’s because the risk is real. In these patients, even small drops in blood pressure or dehydration can trigger lactic acidosis.

Who CAN Take Metformin Safely?

Here’s where things change. If you have:

• Non-alcoholic fatty liver disease (NAFLD) without fibrosis
• Compensated cirrhosis (Child-Pugh Class A)
• Mild elevation in liver enzymes with stable function

…then metformin may not only be safe-it might be helpful.

The American Diabetes Association’s 2023 guidelines now say metformin is appropriate for patients with stable chronic liver disease, including compensated cirrhosis. The European Association for the Study of the Liver is preparing new 2025 guidelines that may even recommend metformin as first-line therapy for NAFLD with diabetes.

Why? Because studies show metformin reduces liver fat, lowers inflammation, and may even slow fibrosis progression. In the ongoing MET-REVERSE trial, the incidence of lactic acidosis in patients with mild liver impairment was just 0.02%-lower than the general diabetic population.

How to Monitor for Lactic Acidosis

If you’re on metformin and have liver disease, you need a simple monitoring plan:

1. Check liver enzymes (ALT, AST) every 3 months
2. Measure serum lactate if you feel unusually tired, nauseous, or have abdominal pain
3. Keep track of kidney function (eGFR) monthly if you’re over 65 or have other risk factors
4. Stop metformin if you’re hospitalized, dehydrated, or having surgery

Don’t wait for symptoms. If you’re scheduled for a CT scan with contrast, stop metformin 48 hours before and don’t restart until you’re eating normally and your kidneys are working fine. Same goes for any major surgery or illness.

What to Do If Lactic Acidosis Happens

If you suspect lactic acidosis-sudden nausea, vomiting, confusion, fast breathing, or low blood pressure-get to a hospital immediately. Don’t wait.

Treatment is straightforward but urgent:

• Stop metformin right away
• Give IV fluids to restore blood pressure
• If pH is below 7.20, give sodium bicarbonate
• If pH is below 7.0 or lactate is over 20 mmol/L, start hemodialysis

Hemodialysis clears metformin from your blood at 170 mL/min-far faster than any other method. CRRT (continuous renal replacement therapy) only clears 30-40 mL/min. That’s why dialysis saves lives.

Metformin vs. Other Diabetes Drugs in Liver Disease

You might wonder: if metformin is risky, what’s better?

• SGLT2 inhibitors (like empagliflozin): Safe in mild liver disease. Reduce heart and kidney risk. May worsen dehydration.
• GLP-1 agonists (like semaglutide): Safe in compensated cirrhosis. Help with weight loss and liver fat. Can cause nausea.
• Insulin: Always safe. But causes weight gain and hypoglycemia.

None of these drugs have the same liver-protective benefits as metformin. For someone with NAFLD and diabetes, metformin is still the best option-if liver function is stable.

Real-World Use: What Doctors Are Actually Doing

In practice, doctors are changing their minds. From 2015 to 2022, metformin use in NAFLD patients rose by 22%, according to FDA adverse event data. Why? Because the data says it’s safe.

A 2023 study in Liver International followed 1,200 patients with NAFLD and type 2 diabetes on metformin for five years. Only two developed lactic acidosis-and both had other major problems: alcohol relapse and kidney failure. The rest? Stable blood sugar, better liver enzymes, no complications.

The fear of lactic acidosis is real. But the fear of not treating diabetes is worse. Uncontrolled diabetes accelerates liver damage. It increases the risk of cirrhosis, liver cancer, and death.

Bottom Line: Safe Use Checklist

Here’s what you need to know to use metformin safely with liver disease:

• ✅ Do use metformin if you have NAFLD or Child-Pugh Class A cirrhosis
• ❌ Do NOT use if you have Child-Pugh Class B or C cirrhosis
• ✅ Monitor liver enzymes every 3 months
• ✅ Stop metformin before surgery or contrast scans
• ✅ Restart only after you’re eating, hydrated, and stable
• ✅ Check lactate if you feel unwell
• ✅ Avoid alcohol completely
• ✅ Don’t take metformin if your eGFR is below 30

Metformin isn’t dangerous because it’s metformin. It’s dangerous when used in the wrong people. The goal isn’t to avoid it-it’s to use it wisely.

What’s Next?

The MET-REVERSE trial results are due in late 2025. If they confirm what early data suggests-that metformin is safe and beneficial in mild liver disease-we may see a major shift in global guidelines. For now, the evidence is already strong enough to support cautious use in stable patients.

Don’t let outdated warnings keep you from a drug that could protect your liver and your life. Talk to your doctor. Get your liver function checked. Ask about lactate levels. Make an informed choice-not a fearful one.