What medication cannot be taken with metformin?: A Guide to Critical Drug Interactions

October 12, 2025 •

3 min read

Over 14 million Americans were prescribed metformin in 2014, making it one of the most widely used diabetes medications. However, patients must be aware of what medication cannot be taken with metformin and other potentially serious drug interactions to ensure their safety and the medication's effectiveness.

Quick Summary

Combining metformin with certain medications or substances can lead to severe complications like lactic acidosis or hypoglycemia. Patients must avoid alcohol and halt metformin use for procedures involving iodinated contrast dye, and be cautious with other drugs that affect blood sugar or clearance.

Key Points

Risk of Lactic Acidosis: Alcohol, iodinated contrast dye, and certain medications like cimetidine, dolutegravir, and carbonic anhydrase inhibitors can dramatically increase the risk of the rare but serious side effect of lactic acidosis.
Hypoglycemia Risk: Combining metformin with other diabetes medications such as insulin, sulfonylureas (glipizide), or meglitinides (repaglinide) requires careful blood sugar monitoring due to the increased risk of low blood sugar.
Temporarily Halt for Imaging: Metformin should be temporarily stopped before and after any medical imaging procedure that involves iodinated contrast dye to protect kidney function and prevent metformin accumulation.
Reduced Efficacy Concerns: Corticosteroids (prednisone), diuretics (hydrochlorothiazide), and some hormonal therapies or antipsychotics can raise blood glucose levels, counteracting metformin's effect.
Underlying Health Conditions: Patients with kidney or liver disease, heart failure, and older adults are at a higher risk for metformin side effects and require more frequent monitoring.
Discuss All Medications: Always inform your doctor or pharmacist about all prescription drugs, over-the-counter medications, and supplements you take to screen for potential interactions.

Dangerous Interactions to Avoid

Metformin is generally safe, but its primary serious risk is a rare condition known as lactic acidosis, where lactate builds up in the bloodstream. Several medications and substances can significantly increase this risk by either elevating lactate levels or impeding metformin's excretion from the body.

Medications that increase lactic acidosis risk

Certain substances and medications should be used with caution or avoided due to their potential to increase the risk of lactic acidosis when taken with metformin:

Alcohol: Excessive or binge drinking significantly raises the risk of lactic acidosis.
Iodinated Contrast Agents: Used in some medical imaging, these dyes can temporarily affect kidney function, leading to metformin buildup. Temporary discontinuation of metformin is recommended.
Carbonic Anhydrase Inhibitors: This group includes some diuretics and seizure medications.
Cimetidine (Tagamet HB): This heartburn medication can reduce the kidneys' ability to clear metformin.
Dolutegravir (Tivicay): An HIV medication that can increase metformin levels.
Ranolazine (Ranexa): Used for chronic chest pain, this drug can interfere with metformin clearance.

Medications Affecting Blood Sugar and Metformin Efficacy

Metformin lowers blood sugar. Other medications can interact by either increasing the risk of low blood sugar (hypoglycemia) or high blood sugar (hyperglycemia).

Increased risk of hypoglycemia

Combining metformin with other diabetes medications increases the risk of hypoglycemia.

Insulin: Requires close monitoring when taken with metformin.
Sulfonylureas (e.g., glipizide, glyburide): These increase insulin release and the risk of low blood sugar.
Meglitinides (e.g., repaglinide): Also increase insulin release and hypoglycemia risk with metformin.

Reduced metformin effectiveness

Some medications can increase blood glucose, counteracting metformin.

Corticosteroids (e.g., prednisone): Known to raise blood sugar.
Thiazide and Loop Diuretics (e.g., hydrochlorothiazide, furosemide): Can increase blood sugar levels.
Hormonal Therapy: Including oral contraceptives, can potentially increase blood glucose.
Certain Antipsychotics (e.g., olanzapine): Some can cause elevated blood sugar.
Certain Antiepileptics (e.g., phenytoin): Can make metformin less effective.

Comparison of Metformin Drug Interactions


Interaction Type	Examples of Interacting Drugs	Primary Risk	Action Required
Increased Lactic Acidosis	Alcohol, iodinated contrast, cimetidine, dolutegravir, carbonic anhydrase inhibitors	Lactic acidosis (serious, potentially fatal)	Avoid or temporarily halt metformin. Consult your doctor immediately.
Increased Hypoglycemia	Insulin, sulfonylureas, meglitinides	Low blood sugar	Close blood sugar monitoring and potential dose adjustment needed.
Reduced Efficacy	Corticosteroids, diuretics, antipsychotics	Hyperglycemia (high blood sugar)	Increased blood sugar monitoring and potential dose adjustment.

Managing Metformin During Medical Procedures

For procedures using iodinated contrast agents, the FDA advises stopping metformin at the time of or before the procedure and resuming 48 hours later, provided kidney function is stable. Always inform your healthcare team about your metformin use before any medical procedure.

Special Precautions and Chronic Conditions

Certain conditions increase the risk of adverse reactions with metformin. Patients with kidney or liver disease, congestive heart failure, and older adults require closer monitoring due to a higher risk of complications like lactic acidosis.

Conclusion

Safe metformin use depends on avoiding critical drug interactions. It is vital to inform healthcare providers of all medications and supplements. Key risks include lactic acidosis from substances like alcohol and contrast dye, and hypoglycemia when combined with other blood-sugar-lowering drugs. Always follow medical advice, especially regarding temporary discontinuation before procedures. For more information, consult resources like the NIH website. Open communication with your healthcare team is essential for safe diabetes management.

Frequently Asked Questions

Excessive or binge drinking of alcohol should be avoided with metformin, as this can significantly increase the risk of a dangerous condition called lactic acidosis. While moderate consumption might be acceptable for some, it is best to discuss your habits with your doctor.

Yes, if the CT scan uses an iodinated contrast dye, you will need to temporarily stop taking metformin. Your doctor will advise you to stop before the procedure and restart 48 hours later, after confirming your kidney function is stable.

Taking metformin with insulin is common for managing type 2 diabetes, but it increases the risk of low blood sugar (hypoglycemia). Close monitoring of your blood glucose is necessary to manage this risk.

Corticosteroids, such as prednisone, can cause an increase in blood sugar levels. This can reduce the effectiveness of your metformin and lead to hyperglycemia (high blood sugar), requiring close monitoring and possible dose adjustments.

Yes, cimetidine (Tagamet HB) is known to interfere with the kidney's ability to clear metformin from the body. This can cause metformin levels to increase, raising the risk of side effects like lactic acidosis.

Some diuretics, particularly thiazides and loop diuretics, can increase blood sugar levels, which can make metformin less effective. Additionally, certain carbonic anhydrase inhibitor diuretics can increase the risk of lactic acidosis. Always discuss your diuretic use with your healthcare provider.

Individuals with underlying health issues such as kidney or liver disease, congestive heart failure, and the elderly are at a higher risk of complications from metformin interactions, particularly lactic acidosis. It is crucial for these patients to be carefully monitored by their doctor.