Metformin is a common prescription drug used as a first-line treatment for type 2 diabetes and prediabetes (a condition in which glucose levels are elevated but not high enough to be diabetes). 

While metformin is generally safe, there are a number of rare and serious side effects. This article will investigate the connections between metformin and one serious potential side effect known as lactic acidosis. 

Close-up of metformin pill

Key Points:

  • Lactic acidosis, a rare but serious side effect of metformin, is characterized by a buildup of lactic acid in the bloodstream, leading to dangerously acidic blood chemistry. 
  • Symptoms of lactic acidosis include abdominal pain, nausea, decreased appetite, persistent diarrhea, muscle cramps, trouble breathing, rapid or shallow breathing, a general sense of weakness, and in severe cases, altered mental status such as confusion or decreased alertness.
  • The FDA warns of the potential risk of metformin causing lactic acidosis. However, research, including a large-scale 2022 study, show no significant association between metformin use and an increased risk of lactic acidosis or levels of lactic acid compared to other diabetes treatments. 
  • The estimated rate of the side effect is low, at about 6.3 cases per 100,000 people each year.
  • Factors increasing the risk of lactic acidosis in those using metformin include kidney problems and a variety of other medical conditions, age over 65, and the use of certain medicines.

How does metformin work?

Metformin is one of the most commonly prescribed medicines in the world. 

This medicine is mainly used to manage blood sugar levels and is used most frequently for people with prediabetes, gestational diabetes (a type of diabetes that occurs during pregnancy), and type 2 diabetes

See more in: Metformin for Prediabetes: The Pros & Cons.

Metformin works by several methods:

  • Lowering the amount of sugar produced by the liver. 
  • Decreasing sugar absorption in the intestines.
  • Increasing insulin sensitivity, allowing individual cells in the body to consume more sugar and use it more efficiently.

Taken together, these three changes decrease the amount of sugar circulating in the blood.

As a result, the average person taking metformin will see their HbA1c (a measure of glucose control over the previous 2 to 3 months) decrease by about a percentage point. 

This translates into significantly lower blood sugar.

Metformin can also aid in weight loss because it helps reduce hunger cues.

Read more in: Metformin and Weight Loss: Can a Pill Help You Lose Weight?

What is lactic acidosis?

Lactic acidosis is a serious medical condition in which lactic acid builds up in the bloodstream, causing the blood chemistry to become dangerously acidic.

Lactic acidosis can have a number of root causes, but it generally is the result of either an underlying medical condition, a poisoning, or a medication-induced side effect.

Learn more in: Metformin Side Effects (Common and Serious).

The symptoms of lactic acidosis vary from person to person but can include: 

  • Abdominal pain or discomfort 
  • Nausea and vomiting
  • Decreased appetite
  • Persistent diarrhea
  • Muscle pain and cramping
  • Increased heart rate
  • Difficulty breathing, rapid breathing, or hyperventilation 
  • General pain that may be difficult to describe 
  • Lethargy, fatigue, or weakness
  • Altered mental status, including drowsiness, confusion, or loss of consciousness

Lactic acidosis may become a life-threatening emergency if untreated. 

Seek emergency medical care immediately if you’re experiencing these symptoms or believe you might have lactic acidosis. 

Can metformin cause lactic acidosis?

The U.S. Food and Drug Administration (FDA) approval for metformin includes a warning about the possibility of the medication causing lactic acidosis. 

However, the rates of lactic acidosis among people taking metformin are very low, which makes it difficult for researchers to confirm whether the medication is to blame or if it’s caused by other underlying factors. 

A large-scale study reported in 2022 examined 4,241 cases of suspected metformin-associated lactic acidosis and found that only a small fraction (9 percent) had sufficient data to support such a diagnosis, underscoring the rarity of this condition. 

The estimated incidence of metformin-related lactic acidosis is about 6.3 cases per 100,000 people per year

Statistically, this means that if 100,000 people were to take metformin for a full year, you would expect no more than roughly 6 instances of a person experiencing this rare side effect. 

While that’s a low number compared to the side effects of other medications, lactic acidosis is a serious condition. It’s important for people taking metformin to be aware of it. 

Are there any risk factors for lactic acidosis?

There are a number of risk factors for experiencing lactic acidosis while taking metformin. 

These risk factors include: 

  • Having kidney problems (renal [kidney] impairment or kidney disease), with risk increasing with the severity of the condition
  • Dehydration
  • Taking medications like topiramate (brand names Topamax, Topiragen) and other carbonic anhydrase inhibitors, which also increase the risk of lactic acidosis
  • Being over age 65 
  • Undergoing a medical imaging procedure that requires you to be dosed with certain IV-administered contrast agents
  • Experiencing acute congestive heart failure
  • Having liver problems or chronic or heavy alcohol use

Recent surgery and a variety of other health conditions, particularly those affecting the liver, heart, or kidneys, may also put you at higher risk of lactic acidosis. 

Review your full health history with your doctor and ask about any procedures you’ll need before starting a new metformin prescription. 

What are the symptoms of lactic acidosis when taking metformin?

The core symptoms of lactic acidosis tend to be similar regardless of whether it is an adverse reaction to metformin or not. 

These symptoms include:

  • Abdominal pain and upset stomach
  • Muscle pain and cramping 
  • Nausea and vomiting
  • Decreased appetite
  • Difficulty breathing, or rapid and shallow breathing
  • Elevated heart rate
  • Lethargy, fatigue, or weakness
  • Altered mental status
  • General pain

According to the FDA, the onset of metformin-associated lactic acidosis is “often subtle, accompanied only by nonspecific symptoms” like malaise (a general feeling of discomfort), difficulty breathing, and drowsiness.

This differs from lactic acidosis from other causes, which tends to appear suddenly.

It’s important to keep in mind that metformin-associated lactic acidosis is uncommon. 

However, because the condition can be debilitating or even fatal if left untreated, you should treat suspected lactic acidosis as a medical emergency and seek care right away.

How long would it take to develop lactic acidosis on metformin?

Lactic acidosis can occur quickly in the case of a metformin overdose.

A clinical case report published in 2020 described a person who significantly overdosed on metformin and had developed lactic acidosis by the time she arrived at an emergency department four hours later.

While acute overdoses can quickly trigger lactic acidosis, it’s important to remain aware of the symptoms of the condition even long after you start taking metformin. 

Because metformin-associated lactic acidosis is so uncommon, there isn’t an established timeframe for how long it typically takes to develop the condition.

Therefore, it’s important to keep your doctor informed of any health conditions or changes that might increase your risk for lactic acidosis. 

How is diabetic ketoacidosis different from lactic acidosis?

Diabetic ketoacidosis (also known as DKA) and lactic acidosis are two distinct medical conditions — although both involve imbalances in the acidity level of the blood. 

Each can be life-threatening, but they result from different underlying causes.

DKA is a serious diabetes complication that can occur when blood sugar levels have been too high (a condition known as hyperglycemia) for too long.

DKA is marked by the presence of ketones (chemical byproducts of the breakdown of fat for energy) in the blood and urine.

This build-up of ketones in the blood leads to an increase in acidic substances called ketone bodies, which makes the blood more acidic and can cause short- and long-term damage.

Lactic acidosis, on the other hand, is a condition where the buildup of lactic acid in the bloodstream causes the blood to become more acidic. 

It can be caused by either increased lactic acid production or an impairment in the body’s ability to clear out lactic acid.

Like DKA, lactic acidosis can also result in significant short and long-term damage and should be considered an emergency.

Both conditions are dangerous and require medical attention right away.

Final thoughts

Although lactic acidosis occurs infrequently in metformin users, the medicine’s potential link to this condition requires a cautious approach. The low incidence of lactic acidosis in metformin users highlights the drug’s overall safety, but it is important to be aware of the potential for this side effect, especially in people with risk factors. 

Regularly speaking with your healthcare provider, being mindful of whether you are experiencing any symptoms, and understanding your personal risk for the condition can help ensure your use of metformin is safe and effective.

Suggested next article: Everything You Need to Know About Metformin.