10 Metformin Drug Interactions to Know

Key Takeaways

Medications that can further lower blood sugar levels, certain diuretics, medicines for acid reflux, hormonal therapy, and corticosteroids can all result in adverse effects and drug interactions with metformin.
When taking metformin, avoid drinking alcohol, as this combination increases your risk of lactic acidosis, a potentially life-threatening health complication.
Drug interactions can increase the risk of other diabetes-related complications. Keep your healthcare providers updated on all your medications to prevent harmful drug interactions.

Metformin belongs to a group of drugs called biguanides. It works by decreasing hepatic glucose production increasing insulin sensitivity, while reducing the glucose absorption in the stomach and intestines. The effects of metformin on glucose metabolism lower high blood sugar. Therefore, it is effective in treating Type 2 diabetes mellitus. Keeping your diabetes under control helps reduce the risk of diabetes-related complications. Metformin is also prescribed off-label for polycystic ovarian syndrome.

However, taking metformin with certain other medicines can lead to potentially dangerous drug interactions and adverse effects such as hypoglycemia (low blood sugar), metformin-associated lactic acidosis, and vitamin B12 deficiency.

Please continue reading to find out some of the other drugs that patients taking metformin should not take or take with caution.

What causes metformin drug interactions?

The absorption, distribution, and excretion of metformin is carried out by certain drug transporter proteins in the body. Co-administration of certain other drugs can affect these proteins and lead to reduced renal clearance of metformin, accumulation of metformin in the body, and more severe side effects. A drug interaction can also lead to increased metformin elimination and lower plasma concentration of the drug, causing reduced therapeutic efficacy and poor glycemic control (blood sugar control).

Drug interactions can cause metformin to be less effective or increase the risk of side effects such as lactic acidosis.

Another significant metformin drug interaction is with other medicines that can lower blood sugar. Examples include insulin, other diabetic medicines, and medications that can lower blood sugar as a side effect.

Before starting metformin, tell your doctor about all the medicines you take to avoid drug interactions and health complications such as severe lactic acidosis.

What drugs should not be taken with metformin?

The following medications should be used with caution in people who are on metformin:

Blood pressure and heart medications

If you have high blood pressure, your doctor may prescribe you a combination of medications, including a diuretic (a water pill) to help remove excess fluids from the body and lower blood pressure. Different types of diuretics can interact differently with metformin.

For example, thiazide diuretics such as hydrochlorothiazide (Microzide) and chlorthalidone can increase blood sugar. As a result, this type of water pill can counteract the effects of metformin, leading to poorly controlled diabetes.

Other diuretics, such as methazolamide and acetazolamide, can also interact with metformin. Metformin by itself has a boxed warning issued by the U.S. Food and Drug Administration (FDA) regarding the risk of lactic acidosis. Combining metformin with this type of diuretic can further increase the risk of lactic acidosis.

Furosemide (Lasix) is another commonly prescribed diuretic. While furosemide does not cause metformin to be less effective, if your kidney function is already declining, combining metformin with furosemide can potentially worsen your kidney function. This is especially concerning in elderly patients (those who are 65 years and older) since kidney function naturally declines with age.

Beta blockers are a drug class used to treat high blood pressure and heart disease such as congestive heart failure. While beta blockers do not directly interact with metformin, it is important to know that beta blocker medications can mask the signs of hypoglycemia (low blood sugar). By blocking the effects of the natural chemical norepinephrine, beta blockers mask the signs of tremor, shakiness, and increased heart rate. Other signs of low blood sugar, such as hunger, confusion, and irritability, are also concealed by beta blockers. Sweating is the only sign of low blood sugar that is not masked by beta blockers.

If you are taking a beta blocker along with metformin or other diabetes medications, follow your doctor’s instructions on blood sugar monitoring to prevent harmful complications caused by low blood sugar. Examples of beta blockers are listed below:

Beta-blockers such as labetalol (Trandate), atenolol (Tenormin), metoprolol (Lopressor, Toprol XL), propranolol (Inderal, Hemangeol, InnoPran) and nadolol (Corgard, Corzide)

Gastroesophageal reflux disease (GERD) medications

H2 (histamine 2) blockers such as ranitidine (Zantac) can reduce the elimination of metformin through the kidneys.
Another H2 blocker is cimetidine (Tagamet), which can increase the risk of lactic acidosis when combined with metformin. This risk is increased in people who have kidney problems, especially severe kidney disease.

Hormonal therapy

Hormone replacement therapy
Oral contraceptives or birth control pills

These hormonal therapies can reduce insulin sensitivity and glucose tolerance, increasing blood sugar in women with PCOS and thus counteracting the effects of metformin.

Other diabetes drugs

Insulin and other medications used to treat diabetes can increase the risk of hypoglycemia (low blood sugar).

Antimicrobials

Certain antibiotics, such as isoniazid (Laniazid) and rifampin
Antiviral agents such as dolutegravir

These medications can interact with metformin through different mechanisms. For example, isoniazid can counteract the effects of metformin by increasing blood sugar levels. The HIV medication dolutegravir reduces the elimination of metformin, which can result in an accumulation of metformin in the body. High levels of metformin can worsen its side effects and increase the risk of lactic acidosis.

Oral steroids

Oral corticosteroids, such as prednisone (Rayos), dexamethasone, and methylprednisolone (Medrol), can increase blood sugar levels by increasing the liver’s resistance to insulin.

Antiepileptic drugs

Anticonvulsants like phenytoin (Dilantin, Phenytek) can make metformin less effective by increasing blood glucose levels.

Another seizure medication called topiramate (Topamax) can also interact with metformin. Combining topiramate with metformin can increase the risk of lactic acidosis.

What is metformin contraindicated with?

Metformin is contraindicated in people with:

A known allergic reaction to metformin hydrochloride.
Kidney problems, such as severe kidney disease, renal impairment, and kidney failure.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis.

Metformin should be temporarily discontinued before and at least 48 hours after radiologic studies that require iodinated contrast materials because the use of these products can result in acute changes in kidney function, leading to an increased risk of developing lactic acidosis.

What should you avoid taking with metformin?

Avoid drinking alcohol while on metformin. This can increase the risk of severe hypoglycemia (low blood sugar).
Avoid starting any new medications without checking with your healthcare provider.
Avoid skipping doses of metformin. If you miss a dose, take metformin as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.
If you take one or more medications known to interact with metformin, discuss your concern with your healthcare provider. You should not stop taking metformin or other prescription medication without talking to your doctor first.

Why do doctors no longer recommend metformin?

Healthcare providers may not recommend metformin for many reasons, one of which is possible drug interactions with your other medicines. Drug interactions can increase the risk of lactic acidosis and other complications. If there are known drug interactions between metformin and your other medications, your healthcare professional may lower your metformin dose, change you to other diabetes medicines to control blood glucose levels, and/or monitor you carefully for side effects. Tell your doctor immediately if you develop any severe symptoms while on metformin.

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