Metformin and Liver Disease: How to Prevent Lactic Acidosis

Metformin is one of the most commonly prescribed diabetes medications in the world. Millions of people take it daily to control blood sugar. But if you have liver disease, your doctor might tell you to stop taking it. Why? Because of a rare but dangerous side effect called lactic acidosis.

What is lactic acidosis, and why does metformin cause it?

Lactic acidosis happens when your body makes too much lactic acid and can’t clear it fast enough. Lactic acid is a natural byproduct of energy production, especially when your cells don’t get enough oxygen. Normally, your liver breaks down lactic acid and turns it back into glucose. But if your liver is damaged, that process slows down-or stops.

Metformin works by reducing how much glucose your liver makes. It also slightly blocks a key energy pathway in your cells (mitochondrial complex I). This can cause lactic acid to build up. In healthy people, this isn’t a problem. Your liver handles it. But if your liver is already struggling, metformin can push you over the edge.

The risk is low-about 3 to 10 cases per 100,000 people per year. But when it happens, it’s serious. About 41% of patients need a breathing machine. Around 28 to 47% of people who develop it don’t survive. That’s why doctors are cautious.

Is metformin always dangerous with liver disease?

No. The old rule-“never use metformin if you have liver disease”-is outdated.

Studies show that people with non-alcoholic fatty liver disease (NAFLD), the most common form of liver disease in people with diabetes, often benefit from metformin. It can reduce liver fat, lower inflammation, and even improve insulin resistance. In fact, some experts now say metformin might be one of the best options for these patients.

The real danger is in advanced liver disease: cirrhosis with poor function (Child-Pugh class B or C). In these cases, the liver can’t clear lactate at all. Even small amounts of metformin can build up and trigger lactic acidosis.

Here’s the split:

• Mild liver disease (NAFLD, Child-Pugh A): Often safe. May even help.
• Severe liver disease (Child-Pugh B or C): Avoid metformin. Too risky.

The American Diabetes Association updated its 2023 guidelines to say metformin is appropriate for patients with stable chronic liver disease-including compensated cirrhosis. But they still warn against it in decompensated disease.

Why do some doctors still say no?

Because guidelines lag behind science.

The Medsafe guidelines from 1998 banned metformin in all liver disease. That rule stuck. Even though newer studies show little to no risk in mild cases, many doctors still follow the old warnings out of habit-or fear of liability.

Dr. John B. Buse, former president of the American Diabetes Association, said in 2023: “The evidence against metformin in non-cirrhotic liver disease is remarkably weak.”

But Dr. Kenneth Cusi, a leading liver and diabetes expert, counters: “In decompensated cirrhosis, the risk isn’t theoretical-it’s life-threatening.”

So it’s not black and white. It depends on how well your liver is working.

How do you know if your liver is okay to use metformin?

Your doctor will check a few things:

• Child-Pugh score: A system that rates liver function from A (mild) to C (severe). If you’re Child-Pugh A, metformin is often fine. B or C? Avoid it.
• ALT and AST levels: Liver enzymes. High numbers mean inflammation or damage.
• Albumin and bilirubin: These show how well your liver is making proteins and clearing waste.
• INR: A blood clotting test. If it’s high, your liver isn’t producing clotting factors properly.

If you have fatty liver but no cirrhosis, your doctor might still prescribe metformin-especially if your blood sugar is hard to control. But they’ll monitor you closely.

What should you do if you’re on metformin and have liver disease?

Follow these steps:

1. Don’t stop cold turkey. If your doctor says to stop, they’ll tell you how. Stopping suddenly can spike your blood sugar.
2. Get your liver tested regularly. Every 3 to 6 months if you’re on metformin and have liver disease. More often if your condition changes.
3. Watch for warning signs. Nausea, vomiting, stomach pain, unusual tiredness, or trouble breathing? Call your doctor right away. These could be early signs of lactic acidosis.
4. Stop metformin before surgery or imaging scans. If you’re getting contrast dye or having surgery, stop metformin 48 hours before. Restart only after you’re eating normally and your kidneys are working fine.
5. Stay hydrated. Dehydration raises your risk. Drink water, especially if you’re sick or in hot weather.

What are the alternatives if you can’t take metformin?

If your liver can’t handle metformin, there are other options:

• GLP-1 receptor agonists (like semaglutide or liraglutide): These help with blood sugar and weight loss. They’re also good for fatty liver. No lactic acidosis risk.
• SGLT2 inhibitors (like empagliflozin or dapagliflozin): Help your kidneys flush out sugar. They also reduce heart and kidney risks. Safe in mild liver disease.
• DPP-4 inhibitors (like sitagliptin): Mild effect on blood sugar. Low risk of side effects. Often used in liver disease.
• Insulin: The most direct option. No liver metabolism needed. But it can cause weight gain and low blood sugar.

Your doctor will pick the best fit based on your overall health, weight, heart and kidney function, and budget.

What if you accidentally take too much?

Metformin overdose is rare-but dangerous. In cases of intentional overdose, lactic acidosis happens in about 9% of cases.

If you take too much:

• Call emergency services immediately.
• Don’t wait for symptoms. Lactic acidosis can develop fast.
• Go to the hospital. Treatment includes IV fluids, sodium bicarbonate to correct acid levels, and possibly dialysis.

Hemodialysis is the most effective way to remove metformin from your blood. It clears it at 170 mL per minute-much faster than your kidneys can on their own.

What’s changing in 2025?

New data is shifting the landscape.

The MET-REVERSE trial, which started in 2021 and ends in late 2025, is studying metformin in people with NAFLD and mild liver impairment. Early results show lactic acidosis in just 0.02% of patients-almost the same as in people with healthy livers.

The European Association for the Study of the Liver (EASL) is drafting new 2025 guidelines that may recommend metformin as a first-line treatment for type 2 diabetes in NAFLD patients.

Meanwhile, extended-release metformin formulations are becoming more common. They release the drug slowly, which may lower the chance of lactic acidosis. But data on liver patients is still limited.

Bottom line: It’s not a yes-or-no question

Metformin isn’t automatically unsafe if you have liver disease. The key is how advanced your disease is.

If you have mild fatty liver and no cirrhosis, metformin may be your best option-it helps your liver and your blood sugar.

If you have advanced cirrhosis, vomiting, confusion, or swelling in your belly, metformin is too risky. Switch to something safer.

Talk to your doctor. Bring your latest blood work. Ask: “Is my liver stable enough for metformin?” Don’t assume it’s off-limits. Don’t assume it’s safe. Get the facts.

Your liver matters. Your blood sugar matters. And with the right info, you can manage both.