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 diabetes medication that’s often a first-choice treatment for Type 2 diabetes. It also has many off-label uses, such as treating prediabetes and polycystic ovary syndrome.

Metformin works by lowering blood glucose (blood sugar) levels. It does this by making the body more sensitive to insulin and decreasing sugar production and absorption. But, like most medications, it has risks, including potential drug interactions to keep in mind.

Metformin interactions at a glance

Certain medications and substances can worsen metformin’s side effects or make it less effective. Some potential interactions may be managed with dosage adjustments or extra monitoring, while others should be avoided altogether. 

Keep these potential metformin interactions in mind:

• Insulin

• Certain oral diabetes medications, such as sulfonylureas and meglitinides

• Medications that increase blood sugar levels, such as corticosteroids like prednisone and thiazide diuretics like hydrochlorothiazide (Inzirqo)

• Carbonic anhydrase inhibitors, such as topiramate (Topamax)

• Medications that increase metformin levels, such as ranolazine (Aspruzyo) 

• Calcium channel blockers, such as amlodipine (Norvasc, Norliqva, Katerzia)

• Thyroid medications, such as levothyroxine (Synthroid, Unithroid, Levoxyl, others)

• Warfarin (Coumadin, Jantoven)

• Furosemide (Lasix, Lasix ONYU, Furoscix)

• Estrogen products

• Birth control pills

• Alcohol

Below, we review seven important metformin drug interactions in more detail and how to manage them.

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Good to know: This list doesn’t reflect every possible metformin interaction. Bring an up-to-date list of your medications to your medical appointments, and let your pharmacist know if anything changes.

1. Insulin

Like metformin, insulin can cause low blood sugar (hypoglycemia) as a side effect. When insulin and metformin are paired together, this risk is amplified.

People with Type 2 diabetes sometimes need to take insulin and metformin together. Combining these medications doesn’t always cause hypoglycemia, but you’ll want to monitor your blood sugar levels closely at home if you’re taking both. This will help you keep track of whether your blood sugar 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

Untreated hypoglycemia can be dangerous and lead to more serious complications. Usually, hypoglycemia can be treated at home with a fast-acting sugar 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. You can also ask your prescriber for a prescription for glucagon or a glucagon-like product to quickly raise blood sugar.

2. Sulfonylureas and meglitinides

Sulfonylureas and meglitinides are two groups of oral diabetes medications. They prompt the body to release more insulin, which can lower blood sugar levels. If you’re taking one of these medications with metformin, there's a risk that your blood sugar 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.

Your healthcare professional may 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.

EXPERT PICKS: WHAT TO READ NEXT

• Beyond metformin: There are other oral treatment options for Type 2 diabetes. Here’s a pharmacist-backed list of alternatives. 

• Risk management: Some side effects are common when taking metformin. Learn more about what you can expect while taking this medication.

• Metformin and alcohol aren’t a good mix: Read on to learn why it's recommended to talk to a healthcare professional before drinking alcohol while taking metformin.

• Your metformin questions, answered: Get the facts on how long it takes metformin to start working, in addition to other essential metformin FAQs.

Still, you should monitor your levels more closely if you take more than one medication that lowers blood sugar. 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 sugar. But some medications can increase blood sugar levels, counteracting the effects of metformin. If metformin is less effective, you could experience high blood sugar (hyperglycemia) levels as a result.

Corticosteroids are perhaps the most well-known group of medications that can increase blood sugar levels. The risk of increased blood sugar 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 managed.

Examples of corticosteroids include:

• Prednisone (Rayos)

• Prednisolone (Pediapred, Orapred ODT)

• Methylprednisolone (Medrol)

• Dexamethasone

Knowing the potential symptoms of high blood sugar can help you catch it early. They 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 sugar and talk to your healthcare professional. And if you start or stop taking a corticosteroid while taking metformin, let your prescriber know. They may want to monitor your blood sugar more closely and possibly adjust your metformin dosage.

4. Other medications that increase blood sugar levels

Medications other than corticosteroids can increase blood sugar 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, FloLipid)

• 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 sugar frequently.

If you stop taking one of the medications mentioned above while taking metformin, there’s a risk of hypoglycemia. Let your healthcare prescriber 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 for it. This includes people with advanced kidney disease or liver disease.

If you take a carbonic anhydrase inhibitor with metformin, it’s important to complete all blood work ordered by your healthcare professional. 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

• Dolutegravir (Tivicay)

• Cimetidine (Tagamet HB)

• Vandetanib (Caprelsa)

If you need to take one of these medications with metformin, your prescriber should advise you on how to keep an eye out for serious side effects, including lactic acidosis. It’s also 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.

What’s more, 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 prescriber 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 prescriber about how much you’re drinking. They can help you decide if metformin is a good medication option for you.

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Written by:

Austin Ulrich, PharmD, BCACP

​​Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. Ulrich’s experience includes direct patient care in hospital and community pharmacies.

Written by:

Kathryn Cannaday, PharmD Candidate

Kathryn Cannaday is currently a pharmacy intern with Ascension St. Vincent Hospital in Indianapolis. She is also currently involved in a year-long experience with Butler University Community Outreach Pharmacy, serving as a medication therapy consultant for the underserved local community.

Edited 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.

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