EnglishEspañol

Diabetes Medication: Side Effects and Drug Interactions

Written by Stephanie Booth, Hirania Luzardo
Medically Reviewed by Jabeen Begum, MD on February 02, 2026

Many type 2 diabetes medications can help manage your blood sugar (also known as blood glucose) and your condition. But just because you’re on one treatment that works well doesn’t mean that it’s the only one you’ll need.

“Diabetes is a very dynamic situation,” says David Cutler, MD, a board-certified family medicine physician at Providence Saint John’s Health Center in Santa Monica, California. “As your weight changes, as you go on to other medications, as you age, or perhaps your kidney or liver function declines, there become needs for altering your medication.”

There are usually signs that it’s time for a new treatment plan. For instance, your blood sugar may stop being well controlled, you could have side effects, or maybe a medication you need for a new condition is known to prevent type 2 diabetes medications from working well.

“It’s hard to predict ahead of time what’s going to cause the change, but it shouldn’t be a surprise when you do need to change things,” says Cutler. “That’s just the nature of treating diabetes.”

Your doctor might change your medication or other aspects of your treatment if you often have high or low blood sugar.

High blood sugar

Keeping your blood sugar within a healthy range lowers your chances of complications and helps you manage other conditions that go along with diabetes. If your glucose readings are trending too high with your current medication, your doctor may decide to change your dose or add another drug.

This can happen even if your medication worked well at first. Sometimes, it just doesn’t do the trick by itself anymore.

If one drug doesn’t manage your blood sugar well enough, your doctor might add a second. If two don’t work, they could add a third. Just remember: Any medication you get will work best when you also make healthy changes, such as watching what you eat and being active, to your daily routine.

Low blood sugar

Diabetes drugs’ side effects sometimes include hypoglycemia. That’s when your blood glucose goes too low. It can make you feel shaky, sweaty, dizzy, and confused, and it can be dangerous.

If you get low blood sugar often, your doctor may need to lower your dosage or change your medication.

It may also be time to change your diabetes medication if its side effects get in the way of your daily life, or if it keeps other drugs you take from doing their job.

A lot of the time, your doctor will need to treat you for more than high blood sugar levels. It’s common for diabetes to go hand in hand with many other conditions, including high cholesterol, high blood pressure, and even depression. The more treatments you have, the more likely it is that the medications you take could interact with each other. Always make sure your doctor knows about all the medications you take, including natural supplements, over-the-counter products, and recreational drugs.

Keep in mind that diabetes medications work differently on everyone. Always talk to your doctor if you have side effects that surprise or concern you. They can give you tips on how to manage them or suggest the next steps that you take. 

Never stop or adjust your diabetes medication without first talking to your doctor.

Biguanides are diabetes medicines you take by mouth. One example is metformin (Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet). Metformin is usually the first drug doctors suggest to treat type 2 diabetes. It helps sugar get into your cells more easily. It also reduces how much sugar your liver naturally makes.

Side effects of metformin include:

  • Nausea
  • Gas
  • Indigestion
  • Throwing up
  • Diarrhea 
  • Headache
  • Sweating more than usual

B-12 deficiency is one of the less common metformin side effects. 

Rarely, metformin can cause a serious condition called lactic acidosis. That’s when too much lactic acid (a chemical your body makes when it breaks down carbohydrates) builds up in your bloodstream. If not treated, it can be life-threatening.

You’re at higher risk of lactic acidosis if you:

  • Are over 65 
  • Regularly drink large amounts of alcohol 
  • Recently had surgery 
  • Have low oxygen levels
  • Have liver or kidney disease

Call 911 or go to a hospital right away if you take metformin and get any of these symptoms:

  • Weakness 
  • Feeling tired, even after resting
  • Changes in your breathing (like long, deep breathing)
  • Belly pain
  • Sudden stomach problems, such as vomiting or diarrhea

Metformin drug interactions

Many drugs can interfere with metformin. They include:

  • Some antivirals
  • Birth control pills
  • Diuretics
  • Medication for high blood pressure or heart disease
  • Steroids
  • Niacin
  • Stimulants (such as some treatments for attention-deficit/hyperactivity disorder)
  • Thyroid medication

It’s not advised to take metformin with contrast dyes you get before CT scans, MRIs, or other imaging tests. It’s also not safe to take it with dofetilide, a medication you take when your heart rhythm is irregular.

Taking metformin at the same time as certain other drugs can lead to low blood sugar. The list includes:

  • Alpha-lipoic acid
  • Androgens
  • Salicylates
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Pegvisomant
  • Prothionamide
  • Quinolones

Sulfonylurea drugs like glimepiride (Amaryl), glipizide (Glucotrol, Glucotrol XL), and glyburide (Micronase, Glynase, and Diabeta) lower blood sugar by helping your pancreas make more insulin. You take them one or two times a day before meals.

The most common side effects of this diabetes medication are low blood sugar and weight gain.

You could also have:

  • An upset stomach
  • Diarrhea
  • Skin rashes
  • Reactions to the sun

Sulfonylureas drug interactions

Many drugs and supplements can change the way sulfonylureas work. Some make them work too well, leading to low blood sugar. Others can cause the opposite effect and raise your blood sugar.

So you must tell your doctor all the drugs and supplements that you take.

Some common drugs or herbs that can affect how sulfonylureas work include:

  • Amiodarone
  • Carbamazepine
  • Co-trimoxazole
  • Dexamethasone
  • Fluconazole
  • Fluoxetine
  • Fluvoxamine
  • Ketoconazole
  • Metronidazole
  • Phenobarbital
  • Rifampin
  • St. John’s wort
  • Voriconazole

Meglitinides, like nateglinide (Starlix) and repaglinide (Prandin), help your pancreas make more insulin. You take them right before you eat. These drugs work a lot like sulfonylureas, but they get into your system faster.

Low blood sugar can be a common side effect.

Meglitinides drug interactions

Some other drugs can affect how your body processes meglitinides. This may make blood sugar too low or too high. Your doctor may need to keep an eye on your blood sugar levels, adjust your dosage, or switch you to a different diabetes medicine.

Drugs that might not mix well with meglitinides include:

  • Azole antifungals
  • Some antibiotics, including azithromycin, clarithromycin, and erythromycin
  • Atorvastatin
  • Deferasirox 
  • Gemfribozil
  • Some high blood pressure medicines, such as calcium channel blockers, beta-blockers, and thiazide diuretics
  • Corticosteroids
  • Estrogen
  • Nicotinic acid
  • Oral contraceptives
  • Phenothiazines
  • Phenytoin 
  • Thyroid supplements
  • Monoamine oxidase inhibitors
  • NSAIDs
  • Probenecid
  • Salicylic acid
  • Sulfonamides

Thiazolidinediones (TZDs) such as pioglitazone (Actos) and rosiglitazone (Avandia) boost the way insulin works in your muscles and fat. These drugs also reduce how much sugar your liver makes. 

These drugs might:

  • Make you retain fluids, leading to swelling
  • Cause weight gain
  • Raise your LDL cholesterol

In the past, TZDs were linked to a few serious side effects, including bone fractures, heart failure, and an increased risk of bladder cancer in women. It’s unclear if these risks are smaller than once believed. Still, you shouldn’t take TZDs if:

  • You have bladder cancer
  • You had bladder cancer in the past
  • You have blood in your urine (pee)
  • You have congestive heart failure

Thiazolidinediones drug interactions

Among the drugs that can interfere with TZDs are:

  • Atorvastatin
  • Bosentan
  • Birth control pills
  • Gemfibrozil (Lopid)
  • Insulin or other diabetes medications
  • Midazolam
  • Nifedipine
  • Nitrates, such as amyl nitrite, isosorbide dinitrate, isosorbide mononitrate, or nitroglycerin
  • Rifampin (Rifadin)
  • Some antifungal drugs
  • Topiramate

In rare cases, pioglitazone has been linked to liver damage. Let your doctor know if you have any of these symptoms:

  • Nausea
  • Vomiting
  • Loss of appetite
  • Pain in the upper right part of your belly
  • Flu-like symptoms
  • Dark pee
  • Fatigue
  • Yellowed skin or eyes
  • Bleeding or bruising that you can’t explain

Alpha Glucosidase Inhibitors Side Effects

Acarbose (Precose) and miglitol (Glyset) are alpha-glucosidase inhibitors (AGIs). You take these diabetes medications with the first bite of each meal. AGIs slow the breakdown of starches, such as potatoes and bread. That prevents your blood sugar from rising too quickly after you eat.

Side effects of diabetes medication like these include gas, diarrhea, and bloating. AGIs may also increase your risk of liver damage. If you have a liver condition, your doctor may prescribe another type of medication instead.

Alpha glucosidase inhibitors drug interactions

Some medications that interfere with alpha-glucosidase inhibitors or vice versa include:

  • Charcoal 
  • Digestive enzymes 
  • Digoxin
  • Diuretics
  • Female hormones
  • Gatifloxacin
  • Isoniazid
  • Phenothiazines
  • Some cold medicines, such as phenylephrine and pseudoepinephrine
  • Some high blood pressure drugs, such as beta-blockers and calcium channel blockers
  • Steroids
  • Thyroid hormones

Talk to your doctor if you take any of these drugs. Remember to also tell them if you smoke, drink alcohol, take recreational drugs, or use supplements, even if you buy them over the counter and the label says they’re “natural.”

Dipeptidyl peptidase 4 (DPP-4) inhibitor medications such as alogliptin (Nesina), linagliptin (Tradjenta), saxagliptin (Onglyza), and sitagliptin (Januvia) help your pancreas release more insulin after meals. Their side effects may include:

  • Sore throat
  • Stuffy nose
  • Headache

You might also run the risk of more serious and long-term complications, including pancreatitis, liver damage, joint pain, and an increased risk of heart failure.

DPP-4 inhibitor drug interactions

Many other drugs can cause issues if you take them at the same time as a DPP-4 inhibitor, including:

  • Atazanavir 
  • Clarithromycin 
  • Gatifloxacin
  • Indinavir
  • Insulin
  • Ketoconazole
  • Nefazodone
  • Rifampin 
  • Ritonavir
  • Saquinavir
  • Sulfonylureas such as glimepiride, glipizide, glyburide
  • Telithromycin

Like with any medication, tell your doctor about any health issues you’ve had in the past, as well as if you’re pregnant, trying to get pregnant, or nursing.

These drugs include canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance). They work in your kidneys and remove extra sugar from your blood through your pee.

SGLT2 inhibitors raise your chances of urinary tract and yeast infections. Rarely, they can cause a life-threatening complication called diabetes-related ketoacidosis (DKA). But they also reduce the risk of kidney disease for people with diabetes and may lower your risk of being in the hospital for heart failure.

SGLT2 inhibitors drug interactions

SGLT2 inhibitors don’t interact with many other drugs, but:

  • Rifampin may make this drug less effective.
  • SGLT2 inhibitors may also raise the amount of digoxin in your body.

These include drugs such as dulaglutide (Trulicity), exenatide (Bydureon, Byetta), lixisenatide (Adlyxin), liraglutide (Victoza), and semaglutide (Ozempic, Wegovy). You usually inject them under your skin. One form of semaglutide, Wegovy, also comes in tablet form.

GLP-1 agonists copy a hormone, GLP-1, that your small intestine makes. That can help improve your blood sugar and help with weight loss.

This diabetes drug’s side effects include:

  • Nausea
  • Vomiting
  • Diarrhea
  • Loss of appetite
  • Headaches
  • Feeling dizzy
  • Quicker heart rate

You’re most likely to notice these side effects when you first start the medication or increase your usual dose.

Rarely, GLP-1 agonists can also lead to severe side effects, such as:

  • Pancreatitis
  • Thyroid cancer
  • Kidney issues or failure
  • Worsened diabetes-related eye issues

GLP-1 agonists drug interactions

Low blood sugar is a serious risk if you take a GLP-1 agonist along with another drug that lowers your glucose, such as:

  • Insulin
  • Sulfonylureas 

GLP-1 agonists can slow down how fast your body absorbs other medications. That can cause them to not work as well. For instance, if you take a birth control pill, you may want to look into a backup form of birth control or switch to another method that won’t be affected.

Tirzepatide (Mounjaro) is a dual GIP/GLP-1 receptor agonist. It works by releasing more insulin when your blood sugar is high, blocking your liver from making more glucose, and helping your body flush out the excess. Because it slows how fast you digest food, tirzepatide can also help with weight loss.

The most common side effects include:

  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Loss of appetite
  • Pain in your belly
  • Indigestion

But sometimes, this diabetes medication’s side effects are more serious, including:

  • Low blood sugar
  • An inflamed pancreas
  • Vision changes
  • Stomach and gallbladder issues
  • Issues with anesthesia during surgery
  • Thyroid tumors
  • Kidney failure

Dual GIP/GLP-1 receptor agonists drug interactions

Like GLP-1 agonists, this type of drug can change how well other medications you take by mouth, like birth control pills, work. Talk to your doctor about how best to manage this.

If other medicines aren’t doing enough, you may need insulin therapy with drugs such as:

  • Awiqli (insulin icodec-abae)
  • Insulin aspart (NovoLog, Fiasp)
  • Insulin detemir (Levemir)
  • Insulin glargine (Lantus, Basaglar, Toujeo)
  • Insulin glulisine (Apidra)
  • Insulin isophane (Humulin, Novolin N)
  • Insulin lispro (Humalog)

Insulin works by moving glucose out of your bloodstream and into your cells.

You inject insulin using a needle, pump, or special pen. Some kinds can be inhaled through your mouth.

The most common insulin side effect is low blood sugar. Although it’s rare, you could also have symptoms such as:

  • Skin reaction (such as lumps of fat forming at the site of the shot)
  • Allergic reaction
  • Insulin antibodies (your immune system starts to “fight” the insulin)

Insulin drug interactions

Many drugs affect the way insulin works in your body and cause your blood sugar to become too low or too high. Your doctor may monitor your blood sugar level, adjust your dose, or change your medicine as a result.

The following are examples of drugs that can interact with insulin:

  • Other diabetes medicines
  • Aspirin
  • Levofloxacin
  • Metoprolol
  • Certain antidepressants, such as fluoxetine and monoamine oxidase inhibitors
  • Some antibiotics, including isoniazid and sulfonamide
  • Some high blood pressure medicines, such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blocking agents, and beta-blockers
  • Some antipsychotic medicines, such as clozapine and olanzapine
  • Some drugs that activate your nervous system, such as albuterol and epinephrine
  • Niacin
  • Corticosteroids
  • Oral contraceptives
  • Estrogens
  • Diuretics
  • Phenothiazines
  • Protease inhibitors
  • Glucagon 
  • Thyroid hormones

Healthy lifestyle changes are an important part of diabetes control, and they can be a factor in whether you need to change your medications.

If you’ve lost weight or begun a regular exercise program, you might need a lower dose of your diabetes medication or a different medication. On the other hand, your doctor might need to step up your treatment plan if you’ve gained weight or become less active.

Always talk to your doctor before you change or stop any medication. Don’t quit taking any medicine without your doctor’s OK.

Type 2 diabetes is a progressive condition. That means it changes over time. Even if you’re following your doctor’s advice exactly, your treatment plan will likely need to be changed.

Doctors are still trying to understand why some people with type 2 diabetes need more medication, or more frequent changes to their medication, than others. Your genes could play a part.

If you need to start treatment for a condition besides diabetes, your doctor will likely want to adjust your medications. 

Factors that can affect your diabetes treatment plan include:

  • Heart issues, including high blood pressure
  • Needing to take antibiotics for an infection
  • Starting medication for a mental health issue
  • Kidney disease or dialysis
  • Taking over-the-counter products (such as pain relievers and cough/cold medication)

All medications come with pros and cons. Your doctor will consider a lot of different factors to figure out a treatment plan that works for you. That can include asking you about your budget, your daily routine, how motivated you are to control your blood sugar, and other health issues that you’re trying to manage.

Your doctor can also discuss possible diabetes medication side effects with you ahead of time. That way, you can figure out ways to avoid or deal with them.

Doctors have over 40 treatment options for type 2 diabetes. Choosing the right options for you can be complex. Your needs may also change over time. Keep all your doctor visits and let them know about any diabetes medication side effects you have, as well as changes to your health. That can help them know when to adjust your treatment.

When should I change my diabetes medication?

Never change or stop diabetes medication on your own. Your doctor can help you understand whether and when it’s time for a change.

What is the best medicine for type 2 diabetes without side effects?

Diabetes medication side effects may be hard to avoid. Like all drugs, they can cause new symptoms. But if you work closely with your doctor, you can find a treatment that you can tolerate well.

Add WebMD as a Preferred Source to see more of our trusted content across Google Search, AI Overviews, and AI Mode