Side Effects and Interactions of Diabetes Drugs

Medically Reviewed by Jennifer Robinson, MD on April 17, 2022

Diabetes drugs can be a great way to keep your blood sugar levels from getting out of whack. But they can sometimes cause side effects or may not mix well with other medicines you take.

Talk to your doctor about what you need to watch out for. Side effects can range from an upset stomach to a serious condition. And other medicines you take can make your diabetes drug stop working -- or even make it work too well.

Know Your Medicines

Different types of diabetes drugs have their own side effects and ways they interact with other medicines.

Biguanides: Metformin (Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet). Metformin is usually the first drug that doctors suggest you try to treat type 2 diabetes. It cuts blood sugar by improving the way your body uses insulin. It also lowers the amount of sugar that the liver makes.

What are the side effects? You may have nausea, gas, bloating, diarrhea, b12 deficiency, and an upset stomach. These problems usually go away in a few weeks, as your body gets used to the medicine. It may also help to take the drug with food.

In rare cases, metformin may cause a serious condition called lactic acidosis. That's when too much lactic acid builds up. Call your doctor right away if you get any of these symptoms:

Do they clash with other drugs? Some drugs may interfere with some of the enzymes that metformin uses to work. Your doctor may need to monitor your blood sugar or adjust your metformin dose if you take any of these:

Anticholinergic drugs, such as dicyclomine (Bentyl) and oxybutynin (Ditropan, Ditropan XL, Oxytrol), may raise the amount of metformin your body absorbs. This may lead to low blood sugar.

Sulfonylureas: Glipizide (Glucotrol, Glucotrol XL), glimepride (Amaryl), glyburide (DiaBeta, Glynase PresTab). These drugs lower your blood sugar by helping your pancreas make more insulin.

What are the side effects? The most common one is low blood sugar. This can make you feel shaky, sweaty, dizzy, and confused.

Severe low blood sugar can be life-threatening. To prevent it, eat regularly and don't skip meals.

Other side effects that you might get are weight gain, dark urine, and an upset stomach. Sulfonylureas can also cause skin rashes and reactions to the sun.

Do they clash with other drugs? About 100 drugs can change the way sulfonylureas work. Some can make them work too well, which may lead to dangerously low blood sugar. Others may cause the medication to be less effective. Your doctor may need to keep tabs on your blood sugar or adjust your sulfonylurea dose.

The medicines that may affect how sulfonylureas work include:

Meglitinides: nateglinide (Starlix), repaglinide (Prandin). They help your pancreas make more insulin. Although these drugs work faster, they don't last as long in the body.

What are the side effects? These medications can lead to low blood sugar and weight gain.

Do they clash with other drugs? Some drugs can affect how your body processes meglitinides. This may cause your blood sugar to become too low or too high. Your doctor may need to keep an eye on your blood sugar levels, adjust your dose, or change your medicine.

The drugs that might not mix well with meglitinides include:

Thiazolidinediones (TZDs): Pioglitazone (Actos), rosiglitazone (Avandia). These drugs boost the way insulin works in the body.

What are the side effects? It may cause you to hang on to fluids in your body, which can lead to swelling. TZDs can also make you gain weight and raise your levels of LDL "bad" cholesterol. They are also linked with serious side effects, such as bone fractures and heart failure as well as being associated with an increase risk of bladder cancer in women.

Do they clash with other drugs? Some drugs block the enzyme that processes TZDs. Your doctor may want to prescribe another medicine if you take one of these medications:

Other medicines, when combined with a TZD, may raise your chance of having heart problems:

  • NSAIDs
  • Sulfonylureas
  • Nitrates

Alpha-glucosidase inhibitors: Acarbose (Precose,) miglitol (Glyset). You take alpha-glucosidase inhibitors with the first bite of each meal. They slow the breakdown of carbohydrates.

What are the side effects? Because these medicines affect your digestion, you may have gas, diarrhea, and stomach pain. They also may cause an increase in blood markers of a stressed liver.

Do they clash with other drugs? Alpha-glucosidase inhibitors may not work as well if you also take digestive enzymes and activated charcoal supplements.

Alpha-glucosidase inhibitors can also make it harder for the body to absorb digoxin. They may also change the way warfarin works. Talk to your doctor if you take either of these drugs.

DPP-4 inhibitors: alogliptin (Nesina),  linagliptin (Tradjenta), saxagliptin (Onglyza), Sitagliptin (Januvia). These medicines help your pancreas release more insulin after meals. They also lower the amount of sugar you make.

What are the side effects? You could get a sore throat, stuffy nose, upset stomach, and diarrhea. You may also run the risk of acute pancreatitis, liver failure, possible worsening heart failure and joint pain

Do they clash with other drugs? Some drugs may affect how much DPP-4 inhibitors are absorbed in the body. Your doctor will want to track your blood sugar levels carefully and watch for potential side effects if you take these medicines:

ACE inhibitors combined with DPP-4 may raise your chance of swelling.

SGLT2 inhibitors: Canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance),  ertugliflozin (Steglatro).

They work in the kidneys and remove extra sugar from your blood through urine.

What are the side effects? These drugs raise your chances of having urinary tract and yeast infections. They may also cause low blood sugar. On the positive side, they may reduce the risk of kidney disease for those with diabetes and can reduce the risk of being hospitalized or dying from heart failure.

Do they clash with other drugs? SGLT2 inhibitors don't interact with many drugs. Rifampin may make the drug less effective. SGLT2 inhibitors may also raise the amount of digoxin in the body.

Insulin therapy: insulin aspart (Novolog), insulin detemir (Levemir), insulin glargine (Lantus), Insulin glulisine (Apidra), insulin isophane (Humulin, Novolin N), insulin lispro (Humalog),.
If other medicines aren't doing enough, you may need insulin therapy. You'll need to inject insulin using a needle and syringe or a pen injector.

What are the side effects? The most common side effect is low blood sugar. You may also have a wide variety of symptoms, such as headaches, rashes, dizziness, anxiety, cough, and dry mouth. Talk to your doctor. Some may go away as your body gets used to the medicine.

Do they clash with other drugs? Some drugs affect the way that insulin works in the body. This may cause your blood sugar to become too low or high. Your doctor may need to monitor your blood sugar level, adjust your dose, or change your medicine if you take some of these:

  • Diabetes medicines
  • Salicylic acid
  • Certain antidepressants, such as fluoxetine and monoamine oxidase inhibitors
  • Some antibiotics, including isoniazid and sulfonamide
  • Fibrates
  • Some high blood pressure medicines, such as ACE inhibitors and angiotensin II receptor blocking agents
  • Certain cholesterol-lowering drugs, including fibrates and niacin
  • Propoxyphene, pentoxifylline and somatostatin analogs
  • Corticosteroids
  • Oral contraceptives
  • Estrogens
  • Diuretics
  • Phenothiazines
  • Danazol (Danocrine)
  • Protease inhibitors
  • Glucagon (GlucaGen)
  • Thyroid medicine

Show Sources


Norman Tomaka, PharmD, media liaison, American Pharmacists Association.

National Institute of Diabetes and Digestive and Kidney Diseases: "Insulin, Medicines & Other Diabetes Treatments."

FDA: "Drug Interactions: What You Should Know," "Humalog: Highlights of Prescribing Information."

Mayo Clinic: "Type 2 Diabetes."

Joslin Diabetes Center: "Oral Diabetes Medications Summary Chart."

American Diabetes Association: "What Are My Options?"

Cleveland Clinic: "Oral Diabetes Medications."

Joslin Diabetes Center: "Sulfonylurea Agents: Oral Hypoglycemic Agents."

Archives of Medical Science: "Sulfonylureas and Their Use in Clinical Practice."

Expert Opinion on Drug Safety: "How Safe Is the Use of Thiazolidinediones in Clinical Practice?"

Diabetes Spectrum: "Drug Interactions of Medications Commonly Used in Diabetes."

Therapeutic Advances in Endocrinology and Metabolism: "Clinical and Pharmacologically Relevant Interactions of Antidiabetic Drugs."

Southern Medical Journal: "Medication Update."

Pharmacy & Therapeutics: "Sodium-Glucose Linked Transporter 2 (SGLT2) Inhibitors in the Management of Type-2 Diabetes: A Drug Class Overview."

© 2022 WebMD, LLC. All rights reserved. View privacy policy and trust info