Key takeaways:
Metformin can interact with many medications, including those that lower blood sugar. This causes a higher risk of hypoglycemia.
Metformin may interact with medications and substances that raise the levels of a substance called lactic acid. This includes carbonic anhydrase inhibitors and alcohol.
Give your healthcare provider and pharmacist a list of all the medications you take before starting metformin. They can check for metformin interactions and talk to you about how to manage them.
Table of contents
If you or someone close to you has Type 2 diabetes, you’ve probably heard of metformin. It’s usually the first-choice medication for this medical condition. It also has many off-label uses, like treating prediabetes and polycystic ovarian syndrome.
Metformin is very effective for treating Type 2 diabetes, but like most medications, it has risks. One such risk is Metformin’s drug interactions. This means that if you take metformin with certain other medications it could result in worse side effects or cause metformin not to work as well. For example, metformin interactions can cause your blood sugar to drop too low (hypoglycemia).
But which interactions can be managed? And which are more serious?
6 metformin interactions to know about
Some metformin interactions may just require closer monitoring by your healthcare provider. But others may require a change in medications.
Here, we’ll review some of the most important interactions you should know about. But keep in mind, this isn’t a complete list. Talk to your healthcare provider and your pharmacist anytime you start a new medication. They can review all the medications and supplements you take, and screen for any interactions.
1. Insulin
Injectable or inhaled insulin medications treat Type 1 and Type 2 diabetes. Both insulin and metformin can cause hypoglycemia as a side effect. When used together, this risk is amplified.
People with Type 2 diabetes may sometimes need insulin and metformin together. Combining these medications doesn’t always cause hypoglycemia. But if you take metformin and insulin, monitor your blood sugar levels closely. This will help you be more aware of changes in your blood sugar. And you should know the signs and symptoms of hypoglycemia. These include:
Faster heartbeat
Feeling hungry
Shakiness and anxiety
Sweating
Dizziness and weakness
Drowsiness
Confusion
Tingling feeling in hands and feet
Hypoglycemia should be treated immediately with a fast-acting sugar source. Examples include a single dose of 4 glucose tablets, 1 tube of glucose gel, or ½ a cup of fruit juice or regular soda. It’s a good idea to carry a fast-acting sugar 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 sugar. If hypoglycemia isn’t treated it can be dangerous.
2. Medications that cause the body to release insulin
Sulfonylureas and meglitinides are two groups of diabetes medications. They cause the body to release more insulin. Increased insulin levels can lower your blood sugar, which is a good thing for people with diabetes. But if you’re taking one of these medications with metformin, there's a risk that your blood sugar drops too low. Examples of sulfonylureas include glipizide (Glucotrol XL), glimepiride (Amaryl), and glyburide (Diabeta, Glynase). Examples of meglitinides include repaglinide and nateglinide (Starlix).
Keep in mind that your healthcare provider may still prescribe a sulfonylurea or meglitinide along with metformin. Combining these medications doesn’t always cause hypoglycemia. But you should monitor your blood sugars more closely. You should also know how to treat hypoglycemia if you start to experience symptoms, as discussed above.
3. Medications that increase blood sugar
If you’re taking metformin, you’re likely relying on its ability to lower blood sugar. But some medications may prevent metformin from working as well. This is because these medications can raise your blood sugar, counteracting the effects of metformin. This could make metformin less effective and cause hyperglycemia (high blood sugar). Medications that can cause hyperglycemia include:
Corticosteroids like prednisone
Thiazide diuretics, like hydrochlorothiazide (Microzide) and chlorthalidone
Antipsychotic medications, like quetiapine (Seroquel), clozapine (Clozaril), chlorpromazine
Phenytoin (Dilantin, Phenytek)
Thyroid medications, like levothyroxine (Synthroid, Levoxyl)
Estrogen-containing birth control pills, like Sprintec (norgestimate/ethinyl estradiol) and Yaz (drospirenone/ethinyl estradiol)
Isoniazid
Being able to recognize symptoms of hyperglycemia is important if you have diabetes. This is especially true if you take any medications that can raise blood sugar. Symptoms of hyperglycemia include:
Feeling thirsty and a dry mouth
Peeing more frequently
Headache
Blurry vision
Nausea
Feeling tired, weak, or achy
Fruity smelling breath
Vomiting
Feeling unusually warm or cold
High blood sugar is the top cause of short-term complications (like diabetic ketoacidosis) and long-term complications (like stroke, chronic kidney disease, and nerve pain) from diabetes. If you’re taking a medication that can cause high blood sugar, monitor your blood sugars 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 stopping any medications you take. They can let you know if your diabetes medications need to be adjusted.
4. Carbonic anhydrase inhibitors
Carbonic anhydrase inhibitors are a group of medications that treat many medical conditions. They include diuretics like acetazolamide and methazolamide. They also include seizure medications like topiramate (Topamax) and zonisamide (Zonegran).
These medications can interact with metformin by raising the risk of a medical condition called lactic acidosis. Metformin has a boxed warning for lactic acidosis. This is the strongest warning the FDA can give a medication. When metformin is combined with other medications or substances that can cause lactic acidosis, the risk is higher.
Lactic acidosis happens when a substance called lactic acid builds up too high in the body. Lactic acidosis is a medical emergency that needs immediate hospital care. It can be fatal if it's not treated. Signs of lactic acidosis include:
Feeling extremely tired
Trouble breathing
Muscle aches
Stomach pain
Lower blood pressure
Slowed heart rate
Lactic acidosis is rare, but it’s more common in certain situations. This includes people with advanced kidney disease and liver disease. If you take a carbonic anhydrase inhibitor and metformin, it’s important to complete all blood work that your healthcare provider recommends for you. This will help them monitor how well your kidneys and liver are working, which can lower your chance of developing lactic acidosis.
5. Medications that prevent the body from getting rid of metformin
Some medications can prevent your body from getting rid of metformin effectively. When this happens, metformin levels can build up in the body. This increases your risk of lactic acidosis.
Examples of medications that prevent metformin removal from the body include:
Ranolazine (Ranexa)
Vandetanib (Caprelsa)
Dolutegravir (Tivicay)
Cimetidine (Tagamet HB)
If you take one of these medications, your healthcare provider may check if there’s an alternative medication they can prescribe to prevent an interaction with metformin. If they can’t change your medication, talk with your provider about the signs and symptoms of lactic acidosis discussed above. Ask your provider if any additional bloodwork is required to monitor this interaction more closely.
6. Alcohol
Alcohol has many different effects on the body. One such effect is that it can raise lactic acid levels in the body, just like metformin can. When you combine alcohol and metformin, the risk of lactic acidosis is higher.
Additionally, alcohol and metformin can both interfere with how vitamin B12 is absorbed. Low levels of vitamin B12 can cause or worsen some health conditions, such as anemia and nerve damage. If you’re taking metformin, your healthcare provider may recommend routine vitamin B12 testing over time.
It’s best to avoid heavy drinking for your overall health, and especially while taking metformin. If you do drink alcohol, talk to your healthcare provider about how much you’re drinking. They can help decide if metformin is a good medication option for you.
The bottom line
Metformin is a first-choice medication option for Type 2 diabetes. But it has potential drug interactions you should know about. Metformin can interact with other diabetes medications, like insulin, sulfonylureas, and meglitinides. It may also interact with medications that can raise blood sugar, like some diuretics and corticosteroids. And it may interact with substances that increase the risk of lactic acidosis. This includes carbonic anhydrase inhibitors, cimetidine, and alcohol.
Always give your healthcare provider and pharmacist a list of the medications you take. They can help you check for potential metformin interactions. If any potential interactions exist, they can talk to you about how best to manage them.
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