Diabetes Medication Interaction Checker
Enter your diabetes medications and other drugs/supplements to see potential interactions. This tool is based on current medical knowledge.
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Combining diabetes medications can save lives - or it can land you in the hospital. Many people with type 2 diabetes take more than one drug to keep their blood sugar in check. But not all combinations are safe. Some pairs can cause your blood sugar to crash dangerously low, while others push it too high. The risks aren’t theoretical. Every year, thousands of people end up in emergency rooms because of unexpected drug interactions. And it’s not always the diabetes meds themselves causing the problem - it’s what they’re mixed with.
Why Some Diabetes Drugs Don’t Play Well Together
Diabetes medications work in different ways. Some tell your pancreas to make more insulin. Others help your body use insulin better. Some stop your liver from dumping out too much glucose. When you mix them, their effects can add up - sometimes in ways no one planned for.
The biggest danger? Hypoglycemia. That’s when your blood sugar drops below 70 mg/dL. Symptoms include shaking, sweating, confusion, and in severe cases, seizures or unconsciousness. Drugs like sulfonylureas (glimepiride, glyburide) and meglitinides (repaglinide, nateglinide) are especially risky because they force your body to release insulin, no matter what your blood sugar level is.
Now add a common antibiotic like clarithromycin or an antifungal like ketoconazole. These drugs block the liver enzymes (CYP3A4 and CYP2C8) that break down repaglinide. The result? Repaglinide sticks around longer than it should. Your body keeps pumping out insulin. Blood sugar plummets. A 2023 study in the Journal of Clinical Endocrinology & Metabolism found that patients on repaglinide who took ketoconazole had hypoglycemic episodes 4 times more often than those on repaglinide alone.
Insulin and Rosiglitazone: A Dangerous Duo
Insulin is powerful. It’s often the last line of defense when other drugs fail. But pairing it with rosiglitazone (Avandia) is a bad idea - and not just because of blood sugar.
Rosiglitazone is a thiazolidinedione. It makes your body more sensitive to insulin. That sounds good, right? But it also causes your body to hold onto fluid. When you add insulin - which also causes fluid retention - the result is swelling in the legs, ankles, and feet. For some people, it becomes heart failure. The FDA issued a black box warning in 2010. Since then, rosiglitazone has been pulled from most European markets and is rarely prescribed in the U.S. Still, some patients are on it. If you’re taking insulin and still on rosiglitazone, talk to your doctor. The risk isn’t worth it.
Metformin and Kidney Stress
Metformin is the most common first-line diabetes drug. It’s cheap, effective, and generally safe. But it’s cleared by your kidneys. If your kidney function drops - even slightly - metformin can build up in your system. That raises your risk of lactic acidosis, a rare but life-threatening condition.
Now add drugs that stress your kidneys. NSAIDs like ibuprofen or naproxen. Diuretics like furosemide. Contrast dyes used in CT scans. Even dehydration from a bad bout of the flu can do it. If you’re on metformin, get your kidney function checked every 3-6 months. If your eGFR drops below 45 mL/min, your doctor should reduce your dose. Below 30? Metformin should stop.
And don’t assume your doctor knows about every supplement you take. Some herbal products - like bitter melon or gymnema - can lower blood sugar too. Combine them with metformin, and you’re playing Russian roulette with your glucose levels.
GLP-1 RAs and SGLT-2 Inhibitors: The Safer Newcomers
The good news? Newer diabetes drugs are much less likely to cause dangerous interactions. GLP-1 receptor agonists (like semaglutide, liraglutide) and SGLT-2 inhibitors (like dapagliflozin, empagliflozin) work differently. They don’t force insulin out. They don’t rely on liver enzymes that are easily blocked.
GLP-1 RAs slow digestion, reduce appetite, and help your pancreas release insulin only when blood sugar is high. That means less risk of hypoglycemia - even when paired with metformin or basal insulin. In fact, the American Diabetes Association now recommends combining GLP-1 RAs with insulin over insulin alone for better control and fewer lows.
SGLT-2 inhibitors make your kidneys flush out extra sugar. They don’t interact with CYP enzymes. They’re safe with most blood pressure meds, statins, and even some antibiotics. The only real concern? Dehydration. If you’re on an SGLT-2 inhibitor and start taking a diuretic or lose fluids from vomiting or diarrhea, your risk of low blood pressure and kidney issues goes up. Stay hydrated. Monitor your symptoms.
What About DPP-4 Inhibitors?
Drugs like sitagliptin, saxagliptin, and linagliptin are often called “gliptins.” They work by keeping your body’s own GLP-1 active longer. Sounds harmless? It is - unless you combine them with a real GLP-1 RA.
The ADA explicitly says: don’t mix DPP-4 inhibitors with GLP-1 receptor agonists. They do the same thing. It’s like turning on two faucets to fill one glass. You get no extra benefit. But you do get more side effects - nausea, pancreatitis risk, and higher cost. There’s no clinical reason to do it. If your doctor suggests this combo, ask why.
Corticosteroids, Diuretics, and Other Hidden Triggers
It’s not just other diabetes drugs that cause trouble. Common medications you might take for other reasons can wreck your blood sugar control.
Corticosteroids - prednisone, dexamethasone - are a major one. Used for asthma, arthritis, or even allergies, they make your liver dump glucose into your bloodstream. If you’re on metformin or a GLP-1 RA, you might need a temporary insulin boost during a steroid course. Don’t wait until your sugar hits 300 mg/dL to act.
Diuretics like hydrochlorothiazide can raise blood sugar too. And if you’re on an SGLT-2 inhibitor? That’s a double hit. Your kidneys are already flushing sugar. Now you’re losing more fluid. Watch for dizziness or dry mouth.
Even quinine - once used for leg cramps - can cause severe hypoglycemia. It’s banned in many countries for that reason, but you might still get it in some supplements or tonic water. Avoid it if you’re on insulin or sulfonylureas.
Somatostatin Analogues: The Wild Card
Octreotide and lanreotide are used for conditions like acromegaly or carcinoid tumors. They’re not diabetes drugs - but they affect them big time.
Somatostatin analogues suppress insulin and glucagon. That sounds like it should help. But it doesn’t. Instead, they cause unpredictable swings. One minute, your sugar crashes. The next, it soars. If you’re on one of these drugs and have diabetes, you’ll need daily glucose checks and likely insulin adjustments. No easy formula exists. It’s trial and error - under close supervision.
What You Can Do Right Now
You don’t need to memorize every drug interaction. But you do need to be smart about your meds.
- Keep a current list of every pill, patch, injection, and supplement you take. Include doses and how often you take them.
- Bring that list to every appointment - even if you think it’s not important.
- Ask your pharmacist: “Could this new drug affect my diabetes meds?” They’re trained to catch these things.
- Use one pharmacy for all your prescriptions. That way, their system can flag dangerous combos.
- Set daily glucose checks if you’re on multiple diabetes drugs. Don’t wait for symptoms.
- Know the signs of low blood sugar: sweating, hunger, trembling, confusion. Keep glucose tabs or juice nearby.
And if you’re ever unsure - call your doctor. Don’t guess. Don’t Google it. A 10-minute call could prevent a hospital trip.
What’s Changing in 2025
New research is focusing on how diabetes drugs interact with gut transporters - not just liver enzymes. For example, DPP-4 inhibitors may be affected by P-glycoprotein blockers like cyclosporine or verapamil. These interactions are still being studied, but they’re why your doctor might avoid certain combos even if they seem harmless on paper.
GLP-1 RAs are now being combined with insulin in fixed-dose pens (like iGlarLixi or Soliqua). These are designed to reduce hypoglycemia risk compared to insulin alone. If you’re on insulin and struggling with lows, ask if one of these is right for you.
Bottom line: Diabetes treatment is personal. What works for someone else might not work for you - or could even hurt you. The goal isn’t just to lower your A1C. It’s to do it safely. That means knowing what’s in your medicine cabinet - and who to ask when something doesn’t feel right.
Can I take ibuprofen with metformin?
Short-term use of ibuprofen with metformin is usually safe for healthy kidneys. But if you have reduced kidney function, have heart failure, or are dehydrated, the combo can raise your risk of lactic acidosis. Always check your eGFR before taking NSAIDs regularly. If you need pain relief long-term, ask about acetaminophen instead.
Is it safe to combine GLP-1 RAs with insulin?
Yes - and it’s often recommended. Studies show that combining GLP-1 RAs like semaglutide with basal insulin leads to better blood sugar control and fewer hypoglycemic episodes than insulin alone. These combos also help with weight loss. The American Diabetes Association supports this approach for people who need more control than insulin can provide alone.
Why can’t I take sitagliptin and semaglutide together?
Both drugs boost the effect of GLP-1 in your body. Taking them together gives you no extra benefit - just more side effects like nausea, vomiting, and a slightly higher risk of pancreatitis. The American Diabetes Association specifically advises against this combo. If you’re on one, stick with it. Don’t add the other unless your doctor has a very specific reason.
Can antibiotics cause low blood sugar with diabetes meds?
Yes - especially azole antifungals like ketoconazole and certain antibiotics like clarithromycin and erythromycin. They block the liver enzymes that break down meglitinides (repaglinide, nateglinide) and some sulfonylureas. This causes those drugs to build up, leading to dangerous hypoglycemia. Always tell your doctor you have diabetes before starting any new antibiotic or antifungal.
Should I stop my diabetes meds before a CT scan?
If you take metformin and are getting a CT scan with contrast dye, you’ll likely be asked to hold it for 48 hours. The dye can stress your kidneys, and combining it with metformin increases lactic acidosis risk. Your doctor will tell you when to restart it - usually after checking your kidney function again. Don’t stop other diabetes meds unless instructed.
Amie Wilde, November 10, 2025
Just got prescribed metformin and ibuprofen for my back pain. Read this and immediately called my pharmacist. She said it’s fine short-term but to skip the NSAIDs if I’m dehydrated. Good thing I didn’t just Google it.