Based on animal studies, some believe that taking metformin with grapefruit juice can lead to lactic acidosis. However, human studies haven’t shown this interaction.

Recall of metformin extended release

In May 2020, the Food and Drug Administration (FDA) recommended that some makers of metformin extended release remove some of their tablets from the U.S. market. This is because an unacceptable level of a probable carcinogen (cancer-causing agent) was found in some extended-release metformin tablets. If you currently take this drug, call your healthcare professional. They’ll advise whether you should continue to take your medication or if you need a new prescription.

Many medications, such as statins and some antihistamines, have a negative interaction with grapefruit. Metformin is used in the treatment of type 2 diabetes.

Does having grapefruit while taking metformin lead to adverse side effects? There’s limited research, but here’s what you need to know.

Metformin is a drug that’s prescribed as the first line of treatment for type 2 diabetes. In people with type 2 diabetes, the body’s cells aren’t able to respond to insulin as well as they should. This means they can’t control the amount of sugar in the blood. Metformin helps people with type 2 diabetes control the level of sugar in their blood in several ways. These include:

  • decreasing the amount of sugar your body absorbs from food
  • decreasing the amount of sugar produced by your liver
  • increasing your body’s response to the insulin that it makes naturally

Metformin can rarely cause a very serious and life threatening condition called lactic acidosis. People with liver, kidney, or heart problems should avoid taking metformin.

There are more than 85 drugs that are known to interact with grapefruit. Of these drugs, 43 of them can lead to serious adverse effects. All forms of grapefruit — including freshly squeezed juice, frozen concentrate, pulp, and the whole fruit — can lead to drug interaction.

Some of the chemicals found in grapefruit can bind to and inactivate an enzyme in the body that’s found in your intestines and liver. This enzyme helps break down the medication you take.

Typically, when you take a drug orally, it’s broken down slightly by enzymes before it reaches the bloodstream. This means that you receive a little less of the drug in your bloodstream than the amount you initially consumed.

But when the enzyme is inhibited (prevented from working as it should) a dramatically larger amount of the drug makes its way into your bloodstream. This leads to a higher risk of overdose. This can happen with certain medications when they interact with the chemicals in grapefruit.

According to the FDA, the following types of drugs can have a negative interaction with grapefruit:

  • statins, such as simvastatin (Zocor) and atorvastatin (Lipitor)
  • drugs for high blood pressure, such as nifedipine (Procardia, Adalat CC)
  • immunosuppressive drugs, such as cyclosporine (Sandimmune, Neoral, Gengraf)
  • corticosteroids used to treat Crohn’s disease or ulcerative colitis, such as budesonide (Entocort EC, Uceris)
  • drugs that treat abnormal heart rhythms, such as amiodarone (Pacerone, Cordarone)
  • antihistamines, such as fexofenadine (Allegra)
  • some anti-anxiety drugs, such as buspirone (BuSpar)

Grapefruit juice doesn’t have an effect on every drug in the categories above. Interaction with grapefruit juice is drug-specific, not drug category-specific.

Additionally, the severity of the interaction can vary as well. This is because some interactions are classified as much more serious than others.

Certain medications are classified as an X-level interaction, which means the interactions are the most serious and you should avoid these combinations. Drugs classified as an X-level interaction with grapefruit can include:

  • amiodarone (Pacerone)
  • budesonide (Entocort, Uceris, Rhinocort Allergy)
  • cyclosporine (Sandimmune, Neoral, Gengraf)

Certain medications are classified as D-level interactions, which means doctors or healthcare professionals should consider changing therapy. These medications can include atorvastatin (Lipitor) and buspirone (BuSpar).

When starting on a new medication, it’s very important that you ask the doctor or pharmacist if you’re able to consume grapefruit or grapefruit-related products.

It’s important to know that metformin isn’t broken down by the same enzyme as the drugs listed above. It’s unprocessed by your body and expelled in your urine.

There’s limited information available on how having grapefruit while taking metformin affects people with type 2 diabetes.

Although grapefruit juice is a good source of potassium and vitamin C, it can interact with some medications, according to the FDA. However, there’s no proof that grapefruit interacts with metformin.

An older study from 2009 discussed the effects of grapefruit with metformin in nondiabetic rats. Some rats were exposed to grapefruit juice and metformin. Others were exposed to metformin alone. Researchers found that there was an increase in the amount of lactic acid production in the rats that were exposed to grapefruit juice and metformin.

The researchers in this study guessed that grapefruit juice enhanced metformin accumulation in the liver. This, in turn, caused the increase in lactic acid production. Because of this, the researchers suggested that drinking grapefruit juice may lead to an increased risk of lactic acidosis in people taking metformin.

However, these results were observed in nondiabetic rats, not in humans with type 2 diabetes. To date, there hasn’t been a case study in humans that indicates that taking metformin with grapefruit juice leads to lactic acidosis.

Taking certain medications while taking metformin can increase the risk of developing lactic acidosis. You should let the doctor know if you’re taking any of the following medications:

  • carbonic anhydrase inhibitors, such as acetazolamide
  • corticosteroids, such as prednisone
  • blood pressure medication, such as amlodipine (Norvasc)
  • anticonvulsants, such as topiramate (Topamax) and zonisamide (Zonegran)
  • oral contraceptives
  • antipsychotic drugs, such as chlorpromazine

Certain drugs can decrease the clearance of metformin in your body. Let a doctor know if you’ve been prescribed any of these drugs in addition to metformin:

  • ranolazine (Ranexa)
  • dolutegravir (Tivicay)
  • cimetidine (Tagamet HB)

Avoid consuming large amounts of alcohol while on metformin. Drinking alcohol while taking metformin increases your risk of developing low blood sugar or even lactic acidosis.

Some general diet guidelines for people with diabetes include the following:

  • Include carbohydrates that come from vegetables, fruits, and whole grains. Be sure to monitor your carbohydrate intake, as this will directly affect your blood sugar.
  • Avoid food that’s high in saturated and trans fats. Instead, consume fats from fish, nuts, and olive oil.
  • Eating up to 35 grams of fiber per day may help control blood glucose levels. Many fresh fruits and vegetables contain dietary fiber.
  • The American Diabetes Association recommends that people with type 2 diabetes follow the U.S. dietary guidelines for sodium intake and try to consume less than 2,300 milligrams of sodium per day.

Drinking grapefruit juice may actually be beneficial if you have diabetes.

According to a 2021 review of literature, eating whole fruits with a lower glycemic load may help glycemic control in people with type 2 diabetes. Consuming up to 133 g of fresh fruit per day may lower the risk of complications and mortality in people with diabetes. The study’s author pointed out that eating whole fruit may be protective against developing type 2 diabetes and may also replace an energy-dense snack.

Another review from 2019 suggests that naringenin, a flavonoid found in high levels in grapefruit, has been shown to have antidiabetic properties, in addition to other health benefits. This flavonoid is associated with weight loss and improved insulin resistance. It has been found to improve hyperglycemia and high cholesterol.

Grapefruit does lead to negative interactions with some medications. However, there are no case studies in which consuming grapefruit juice while taking metformin led to adverse effects in humans.

There’s some promising experimental evidence that including grapefruit in your diet can help promote weight loss and lower fasting glucose levels.

If you’re taking metformin and are concerned about drug-drug interactions or food-drug interactions, talk with your healthcare professional.