Do I Need to Change My Type 2 Diabetes Medication?

Medically Reviewed by Michael Dansinger, MD on March 16, 2023
8 min read

Type 2 diabetes medications offer many options to help manage your blood sugar (also known as blood glucose) and your condition. But sometimes a medication doesn’t get the job done, causes bothersome side effects, or doesn’t mix well with other medications you take. 

If your treatment isn’t working well enough or doesn’t feel right for you, talk to your doctor. They may tell you it’s time to change your treatment plan. 

Your doctor might need to change your medication, your dosage, or other aspects of your treatment if you often have: 

High blood sugar 

It’s important to keep your blood sugar within a healthy range. This 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 can 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.

Low blood sugar

Sometimes, diabetes medications can make your blood glucose go too low. It can make you feel shaky, sweaty, dizzy, and confused. Your doctor calls this hypoglycemia, and it can be dangerous. 

If it happens often, your doctor may need to lower your dosage or change your medication.


It may also be time to change your diabetes medication if it causes side effects that interfere with your life, or if it interacts with other drugs you take.

Keep in mind that some side effects are temporary as your body gets used to a new drug. Talk to your doctor if you have serious side effects or if they don’t go away. They can tell you the best ways to deal with them. 

Different types of diabetes drugs work in different ways. Each has its own possible side effects and ways they can interact with other medicines you take. Always make sure your doctor knows about any medications you’re taking. 

Biguanides are diabetes medicines you take by mouth such as metformin (Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet). Metformin is usually the first drug doctors suggest to treat type 2 diabetes. It cuts blood sugar by improving the way your body uses insulin. It also reduces how much sugar your liver makes.

When you take these drugs, you could have:

  • Nausea
  • Gas
  • Bloating
  • Diarrhea or an upset stomach
  • A deficiency of vitamin B12 

These problems are usually temporary. It can help to take the drug with food. 

It’s rare, but 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. Call your doctor right away if you get any of these symptoms:

  • Weakness or unusual tiredness
  • Trouble breathing
  • Muscle pain that's not normal
  • Sudden stomach problems, such as vomiting or diarrhea
  • Loss of appetite

Some other drugs can interfere with 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:

  • Amiloride (Midamor)
  • Cephalexin (Daxbia, Keflex)
  • Cimetidine (Tagamet)
  • Digoxin (Lanoxicaps, Lanoxin)
  • Procainamide
  • Pyrimethamine (Daraprim)
  • Quinidine (Quinidex)
  • Quinine
  • Trimethoprim (Primsol)
  • Vancomycin (Vancocin)

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

Sulfonylurea drugs like glimepiride (Amaryl), glipizide (Glucotrol, Glucotrol XL), and glyburide (DiaBeta, Glynase PresTab) lower blood sugar by helping your pancreas make more insulin. You take them by mouth.

Their most common side effect is low blood sugar. Other side effects you might get are:

  • Weight gain
  • Dark urine
  • An upset stomach
  • Skin rashes
  • Reactions to the sun

Many drugs can change the way sulfonylureas work. Some make them work too well, leading to low blood sugar. Others can cause the medication to be less effective. If you’re taking any of these other drugs, your doctor may need to keep tabs on your blood sugar or adjust your sulfonylurea dose.

Medicines that can affect how sulfonylureas work include:

  • Azole antifungals, including fluconazole and ketoconazole
  • Some antibiotics, such as chloramphenicol, ciprofloxacin, clarithromycin (Biaxin), co-trimoxazole, isoniazid (Nydrazid), rifampin, and sulfasalazine (Azulfidine, Azulfidine EN-tabs, Gantrisin Pediatric, Sulfazine, Sulfazine EC, co-trimoxazole, Zonegran)
  • Cholesterol-lowering drugs, such as clofibrate and gemfibrozil
  • Tricyclic antidepressants
  • H2 blockers
  • Gout medications, such as probenecid
  • Some high blood pressure medicines, including ACE inhibitors and bosentan
  • Beta-blockers
  • Corticosteroids
  • Calcium channel blockers
  • Oral contraceptives
  • Thiazide diuretics
  • Thyroid medicines

Meglitinides, like nateglinide (Starlix) and repaglinide (Prandin), help your pancreas make more insulin. While these drugs work faster than other diabetes medications you take by mouth, they don't last as long in your body.

Their side effects can include low blood sugar and weight gain.

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
  • Certain antibiotics, including isoniazid and rifampin
  • Some high blood pressure medicines, such as calcium channel blockers, beta-blockers, and thiazide diuretics
  • Corticosteroids
  • Estrogen
  • Nicotinic acid
  • Oral contraceptives
  • Phenothiazines
  • Phenytoin (Dilantin, Phenytek)
  • Thyroid supplements
  • Monoamine oxidase inhibitors
  • NSAIDs
  • Probenecid
  • Salicylic acid
  • Sulfonamides

Thiazolidinediones (TZDs) like pioglitazone (Actos) and rosiglitazone (Avandia), boost the way insulin works in the body.

These drugs might:

  • Make you retain fluids, leading to swelling
  • Cause you to gain weight
  • Raise your levels of LDL or "bad" cholesterol 

They’ve also been linked to a few serious side effects, including bone fractures, heart failure, and an increased risk of bladder cancer in women.

Some drugs block the enzyme that processes TZDs. Your doctor may prescribe a different diabetes drug if you take one of these medications:

  • Fluoxetine (Prozac)
  • Gemfibrozil (Lopid)
  • Ketoconazole (Nizoral)
  • Rifampin (Rifadin)
  • Trimethoprim (Primsol)

Some other medicines, when you take them with a TZD, may raise your risk of heart problems:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or naproxen
  • Sulfonylureas
  • Nitrates

In rare cases, pioglitazone has been linked to liver damage. If you take it, or a combination drug that contains it (Actoplus Met, Duetact), call your doctor if you have:

  • Nausea
  • Vomiting
  • Fatigue
  • Loss of appetite
  • Shortness of breath
  • Severe swelling
  • Dark pee

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

Because they affect your digestion, their side effects include gas, diarrhea, and stomach pain. They also may cause an increase in blood markers that can indicate a stressed liver.

Alpha-glucosidase inhibitors may not work as well if you also take digestive enzymes or activated charcoal supplements.

They can also make it harder for your body to absorb digoxin, and change the way warfarin works. Talk to your doctor if you take any of these drugs.

DPP-4 inhibitor medications like 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
  • Upset stomach
  • Diarrhea

 You might also run the risk of acute pancreatitis, liver failure, possible worsening heart failure, and joint pain.

Some other drugs might affect how much DPP-4 inhibitors are absorbed in the body. Your doctor will track your blood sugar levels carefully and watch for potential side effects if you take:

  • Atazanavir (Reyataz) and ritonavir (Norvir)
  • Clarithromycin (Biaxin) and rifampin (Rifadin, Rimactane)
  • Diltiazem (Cardizem)
  • Ketoconazole (Nizoral, Xolegel)

If you take ACE inhibitors with DPP-4s, it could lead to swelling.

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

They raise your chances of urinary tract and yeast infections, and can cause low blood sugar. But they also reduce the risk of kidney disease for people with diabetes and reduce your risk of being hospitalized or dying from heart failure.

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

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

These include drugs like dulaglutide (Trulicity), exenatide extended release (Bydureon BCISE), exenatide (Byetta), semaglutide (Ozempic), liraglutide (Saxenda, Victoza), lixisenatide (Adlyxin), and semaglutide (Ozempic, Rybelsus).

These medications can help improve your blood sugar and might also lead to weight loss.

They can cause side effects like:

  • Nausea
  • Vomiting
  • Diarrhea
  • Possible pancreatitis
  • Injection site reactions
  • Renal issues or renal failure

Tirzepatide (Mounjaro) is a dual GIP/GLP-1 receptor agonist. It can lower your glucose levels and help with weight loss. It has heart benefits as well. This drug also has a low risk of hypoglycemia (low blood sugar). 

Its side effects may include:

  • A quicker heart rate
  • Nausea
  • Vomiting
  • Diarrhea
  • Pain in your bellyabdomen
  • Possible pancreatitis
  • Acute gallbladder disease
  • Renal failure

If other medicines aren't doing enough, you may need insulin therapy with drugs like:

  •  Insulin aspart (Novolog)
  • Insulin detemir (Levemir)
  • Insulin glargine (Lantus)
  • Insulin glulisine (Apidra)
  • Insulin isophane (Humulin, Novolin N)
  • Insulin lispro (Humalog)

You inject insulin using a needle and syringe or a pen injector.

Its most common side effect is low blood sugar. You may also have symptoms such as:

  • Headaches
  • Rashes
  • Dizziness
  • Anxiety
  • Cough
  • Dry mouth.

 Some drugs affect the way insulin works in your body and cause your blood sugar to become too low or high. Your doctor may monitor your blood sugar level, adjust your dose, or change your medicine if you take any of these:

  • Other 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

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. 

If you need to start treatment for a condition besides diabetes, your doctor may want to change your medications. Factors that can affect your diabetes treatment plan include:

  • Kidney disease or dialysis
  • Liver disease
  • Heart failure
  • HIV treatments, which can raise blood sugar and cause weight gain
  • Heavy drinking
  • Age