7 Metformin Interactions You Should Know About

If you or someone close to you has Type 2 diabetes, you’ve probably heard of metformin. It’s an oral antidiabetic medication that’s often a first-choice treatment for Type 2 diabetes. It also has many off-label uses, like treating prediabetes and polycystic ovarian syndrome.

Metformin works by lowering blood glucose (sugar) levels. It does this by making the body more sensitive to insulin and decreasing glucose production and absorption. But, like most medications, it has risks, including potential drug interactions. Taking metformin with certain medications and substances can result in worsened side effects or reduce metformin’s effectiveness.

Below, we review seven important metformin drug interactions to be aware of.

Promotional Disclosureinfo_outlined

SPECIAL OFFER

Save over 40% on Qsymia with GoodRx

Discover the once daily Qsymia for weight management. Qsymia is for adults and children 12-17 in combination with a healthy diet and regular exercise.

Save now

1. Insulin

Like metformin, injectable and inhaled insulin medications, which treat Type 1 and Type 2 diabetes, can cause low blood glucose (hypoglycemia) as a side effect. When insulin and metformin are taken together, this risk is amplified.

People with Type 2 diabetes may sometimes need to take insulin and metformin together. Combining these medications doesn’t always cause hypoglycemia, but you’ll want to monitor your blood glucose levels closely at home if you’re taking both. This will help you keep track of whether your blood glucose drops too low (below 70 mg/dL). 

You should also watch for signs and symptoms of hypoglycemia, including:

• Faster heartbeat

• Feelings of hunger

• Shakiness and anxiety

• Sweating

• Dizziness and weakness

• Drowsiness

• Confusion

• Tingling feeling in hands and feet

Promotion disclosure

Metformin

Avg retail price

$21.99(Save 62.16%)

GoodRx discount

$8.32

See all discounts

How it works

Use GoodRx to find medications, pharmacies, and discounts.

GoodRx discounts can help you pay less for your prescription.

Bring your free coupon or savings card to the pharmacy.

If hypoglycemia isn’t treated, it can be dangerous and lead to seizures or unconsciousness. Usually, hypoglycemia can be treated at home with a fast-acting glucose source. 

Examples of fast-acting glucose sources include a single dose of 4 glucose tablets, 1 tube of glucose gel, or half a cup of fruit juice or regular soda. It’s a good idea to carry a fast-acting glucose source with you at all times. You can also ask your healthcare provider for a prescription for glucagon or a glucagon-like product to quickly raise blood glucose. Glucagon works by triggering the liver to release glucose.

2. Sulfonylureas and meglitinides

Sulfonylureas and meglitinides are two groups of oral diabetes medications. They cause the body to release more insulin, which can lower blood glucose levels. If you’re taking one of these medications with metformin, there's a risk that your blood glucose will drop too low, causing hypoglycemia. Examples of sulfonylureas include glipizide (Glucotrol XL), glimepiride (Amaryl), and glyburide (Diabeta, Glynase). Examples of meglitinides include repaglinide and nateglinide.

Keep in mind that your healthcare provider may still prescribe you a sulfonylurea or meglitinide along with metformin. Combining these medications doesn’t always cause hypoglycemia. In fact, in some cases, metformin is combined with a sulfonylurea or meglitinide in a single pill. For example, glipizide and metformin are available in a combination tablet. 

Still, you should monitor your levels more closely if you take more than one medication that lowers blood glucose. And, as discussed above, you should also know how to treat hypoglycemia if you start to experience symptoms.

3. Corticosteroid medications like prednisone

If you’re taking metformin, you’re likely relying on its ability to lower blood glucose. But some medications can increase blood glucose levels, counteracting the effects of metformin. If metformin is less effective, you could experience high blood glucose (hyperglycemia) levels as a result.

Corticosteroids are perhaps the most well-known group of medications that can increase blood glucose levels. The risk of increased blood glucose is greatest for people who take high dosages of corticosteroids for a long period of time. The risk is also higher for people whose diabetes is not well controlled. 

Examples of corticosteroids include:

• Prednisone (Rayos)

• Prednisolone (Pediapred, Orapred ODT)

• Methylprednisolone (Medrol)

• Dexamethasone

Being able to recognize symptoms of hyperglycemia is important. These symptoms include:

• Thirst 

• Dry mouth

• More frequent urination

• Headache

• Blurry vision

• Nausea and vomiting

• Tiredness, weakness, or achiness

• Fruity smelling breath

• Unusually warm or cold sensation

If you experience any of these symptoms, check your blood glucose and then talk to your provider. And if you start or stop taking a corticosteroid while taking metformin, let your provider know. They may want to monitor your blood glucose more closely and possibly adjust your metformin dosage.

4. Other medications that increase blood glucose levels

There are medications other than corticosteroids that can increase blood glucose levels. As with corticosteroids, these medications can make metformin less effective and lead to hyperglycemia. 

Examples of medications that may cause hyperglycemia when combined with metformin include:

• Thiazide diuretics like hydrochlorothiazide (Microzide) 

• Antipsychotic medications like olanzapine (Zyprexa)

• Beta blockers like metoprolol (Lopressor)

• Statins like simvastatin (Zocor)

• Phenytoin (Dilantin, Phenytek)

• Isoniazid

Hyperglycemia can cause both short-term complications (like diabetic ketoacidosis) and long-term complications (like stroke, kidney disease, and nerve pain) from diabetes. If you’re taking a medication that can cause hyperglycemia, monitor your blood glucose frequently.

If you stop taking one of the medications mentioned above while taking metformin, there’s a risk of hypoglycemia. Let your healthcare provider know before you stop taking any medications, so they can adjust your metformin dosage if needed. 

5. Carbonic anhydrase inhibitors

Carbonic anhydrase inhibitors are a broad group of medications that treat many medical conditions. This group includes diuretics (water pills), like acetazolamide, and seizure medications like topiramate (Topamax) and zonisamide (Zonegran).

Metformin has a boxed warning (the strongest FDA medication warning) for a condition called lactic acidosis. When metformin is combined with other medications or substances that can cause lactic acidosis — including carbonic anhydrase inhibitors — the risk is higher.

Lactic acidosis happens when a substance called lactic acid builds up in the body. This is a medical emergency that requires immediate hospital care, as it can be fatal if it's not treated. Symptoms of lactic acidosis include:

• Extreme tiredness

• Rapid breathing

• Muscle aches

• Nausea and vomiting

• Lowered blood pressure

• Slowed heart rate

While lactic acidosis is rare, people with certain health conditions may be at greater risk. This includes people with advanced kidney disease and liver disease. If you take a carbonic anhydrase inhibitor with metformin, it’s important to complete all blood work ordered by your healthcare provider. This will help them monitor how well your kidneys and liver are working, which can lower your chance of developing lactic acidosis.

6. Medications that increase metformin levels

Some medications can prevent your kidneys from getting rid of metformin effectively. When this happens, metformin levels can build up in the body. This increases your risk of metformin side effects like nausea, diarrhea, and lactic acidosis.

Examples of medications that may prevent the kidneys from getting rid of metformin include:

• Ranolazine

• Vandetanib (Caprelsa)

• Dolutegravir (Tivicay)

• Cimetidine (Tagamet HB)

If you need to take one of these medications with metformin, your healthcare provider will advise you on how to monitor yourself for serious side effects, including lactic acidosis. However, it’s a good idea to ask them if any additional blood work is required to monitor this interaction more closely.

7. Alcohol

Alcohol has many different effects on the body. One effect is that it can raise your lactic acid levels, like metformin. So, when you combine alcohol and metformin, the risk of lactic acidosis is higher.

Additionally, alcohol and metformin can both block vitamin B12 absorption. Low levels of vitamin B12 can cause or worsen certain health conditions, like anemia and nerve damage. If you’re taking metformin, your healthcare provider may check your vitamin B12 routinely (at least once a year).

It’s best to avoid heavy drinking for your overall health, but it’s especially important while taking metformin. If you do drink alcohol, talk to your healthcare provider about how much you’re drinking. They can help you decide if metformin is a good medication option for you.

When should you contact your healthcare provider about metformin interactions?

Before you start taking metformin and during treatment, make sure your healthcare team has a complete list of all the medications and over-the-counter products you take. (This also means updating them if you stop taking any medications.) That way, they can check for potential metformin interactions.

Your provider will decide if you can continue to take medications that may interact with metformin. While some interactions are best avoided, others may be managed with dosage changes or more frequent monitoring of blood glucose levels. 

It’s also a good idea to be aware of the symptoms of hypoglycemia, hyperglycemia, and lactic acidosis, as discussed above. That way, you can contact your provider if you notice any unusual symptoms while taking metformin, or seek emergency care if your symptoms seem severe. 

Why trust our experts?

Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Our editorial standards

Meet our experts