Understanding Insulin Degludec Drug Interactions

If you take Insulin Degludec (Tresiba), you should know that many common medications can affect how well it works — or increase your risk of side effects. Some drugs make insulin work too well, dropping your blood sugar dangerously low. Others fight against it, making your blood sugar harder to control.

This guide covers the key drug interactions you need to be aware of, including prescription medications, over-the-counter drugs, supplements, and even food and alcohol.

How Drug Interactions Work with Insulin

Drug interactions with insulin generally fall into two categories:

• Drugs that increase hypoglycemia risk — These enhance insulin's glucose-lowering effect or have their own blood sugar-lowering properties, making dangerous lows more likely.
• Drugs that decrease insulin's effect — These raise blood sugar or counteract insulin, potentially making your diabetes harder to control.

There's also a third category: drugs that mask the symptoms of low blood sugar, which is dangerous because you might not realize you're going low until it becomes severe.

Medications That Can Increase Hypoglycemia Risk

When combined with Insulin Degludec, these medications may cause your blood sugar to drop lower than expected. Your doctor may need to reduce your insulin dose or monitor you more closely:

Other Diabetes Medications

• Sulfonylureas — Glipizide (Glucotrol), Glyburide (DiaBeta), Glimepiride (Amaryl)
• GLP-1 receptor agonists — Semaglutide (Ozempic, Rybelsus), Liraglutide (Victoza), Dulaglutide (Trulicity)
• Meglitinides — Repaglinide (Prandin), Nateglinide (Starlix)

Blood Pressure and Heart Medications

• ACE inhibitors — Lisinopril, Enalapril, Ramipril
• ARBs — Losartan (Cozaar), Valsartan (Diovan)

Psychiatric and Neurological Medications

• MAO inhibitors — Phenelzine (Nardil), Tranylcypromine (Parnate), Selegiline
• Fluoxetine (Prozac) — Can enhance insulin sensitivity

Pain and Inflammation Medications

• Salicylates — High-dose aspirin (not typical low-dose daily aspirin)
• Pentoxifylline (Trental)

Other

• Sulfonamide antibiotics — Sulfamethoxazole/Trimethoprim (Bactrim)
• Fibrates — Fenofibrate (Tricor), Gemfibrozil (Lopid)

Medications That Can Decrease Insulin's Effect

These drugs may raise your blood sugar, meaning you might need a higher Insulin Degludec dose. Never adjust your dose on your own — always work with your doctor:

Steroids

• Corticosteroids — Prednisone, Dexamethasone, Methylprednisolone, Hydrocortisone. Even short courses can significantly raise blood sugar.

Hormonal Medications

• Oral contraceptives — Birth control pills can affect blood sugar levels
• Thyroid hormones — Levothyroxine (Synthroid) at higher doses
• Danazol — Used for endometriosis

Diuretics

• Thiazide diuretics — Hydrochlorothiazide (HCTZ), Chlorthalidone

Psychiatric Medications

• Atypical antipsychotics — Olanzapine (Zyprexa), Clozapine (Clozaril), Quetiapine (Seroquel). These are well-known to cause insulin resistance and weight gain.

Other

• Sympathomimetics — Albuterol (ProAir, Ventolin), Epinephrine
• Protease inhibitors — Used in HIV treatment
• Isoniazid — Tuberculosis medication
• Niacin — High-dose vitamin B3 (used for cholesterol)

Medications That Mask Hypoglycemia Symptoms

• Beta-blockers — Metoprolol (Lopressor), Atenolol (Tenormin), Propranolol (Inderal), Carvedilol (Coreg). These can hide the warning signs of low blood sugar — especially rapid heartbeat and tremor. You might not feel a low coming on until it's severe. If you take a beta-blocker with insulin, be extra vigilant about checking your blood sugar.

Thiazolidinediones: A Special Warning

Pioglitazone (Actos) and Rosiglitazone (Avandia), when combined with Insulin Degludec, can cause fluid retention and increase the risk of heart failure. Watch for sudden weight gain, swelling in your legs or ankles, and shortness of breath. Report these symptoms to your doctor immediately.

Supplements and OTC Medications to Watch

• High-dose aspirin — Can lower blood sugar (low-dose daily aspirin is generally fine)
• Chromium supplements — May enhance insulin sensitivity
• Cinnamon supplements — Some evidence of blood sugar-lowering effects; talk to your doctor
• Alpha-lipoic acid — May increase insulin sensitivity
• Decongestants containing pseudoephedrine (Sudafed) — Can raise blood sugar

Food and Drink Interactions

Alcohol

Alcohol is the most important dietary interaction with insulin. It can increase or decrease your blood sugar unpredictably:

• Drinking on an empty stomach can cause dangerous hypoglycemia hours later
• Sugary mixed drinks can spike blood sugar initially, then cause a crash
• Moderate alcohol consumption (1–2 drinks) with food is generally okay for most people, but check with your doctor
• Never drink heavily while on insulin — the risk of severe hypoglycemia is real

Food

No specific foods need to be avoided with Insulin Degludec, but carbohydrate intake directly affects how much insulin you need. Work with your doctor or a diabetes educator on carb counting and meal planning.

What to Tell Your Doctor

Before starting Insulin Degludec or any time your medications change, make sure your doctor knows about:

• All prescription medications you take — including those from other doctors
• Over-the-counter medications — Especially pain relievers, cold medicines, and allergy medications
• Supplements and vitamins — Including herbal products
• Alcohol use — Be honest about how much and how often you drink
• Any recent medication changes — Starting or stopping a medication can shift your insulin needs

Keep a current medication list on your phone or in your wallet. Bring it to every appointment and pharmacy visit.

Final Thoughts

Drug interactions with Insulin Degludec are manageable, but you need to know about them. The biggest risks come from medications that increase hypoglycemia (other diabetes drugs, ACE inhibitors, MAO inhibitors) or those that mask its symptoms (beta-blockers). Steroids and atypical antipsychotics can push your blood sugar in the opposite direction.

The key is communication: keep your healthcare team informed about everything you take. For more about side effects, see our Insulin Degludec side effects guide. And if you need help finding Tresiba, Medfinder can help you locate it in stock near you.