Reviewed by: HU Medical Review Board | Last reviewed: August 2023

Sulfonylureas are a class of drugs used to treat people with type 2 diabetes (T2D). They work by triggering cells in the pancreas to release insulin. This helps lower blood sugar levels. Sulfonylureas are only useful if these particular cells – called beta cells – work.

Sulfonylureas are one of the oldest drugs used to treat T2D. But they are usually not the first treatment option for T2D. Your doctor may suggest sulfonylureas if lifestyle changes and other treatments do not control blood sugar. Talk to your doctor about the benefits and risks of sulfonylureas.

How do sulfonylureas work?

Sulfonylureas work by activating "beta cells." Beta cells are cells in the pancreas that make and release insulin. Sulfonylureas block proteins on the surface of beta cells that regulate ion levels. This leads to higher levels of calcium inside cells.1

Higher levels of calcium in the beta cells improves their ability to put out insulin. It also makes beta cells more responsive to glucose. In other words, the pancreas releases more insulin at all blood sugar levels. This can help lower blood sugar for people with T2D.1

Sulfonylureas are common because they are cheaper than other options. But they are not usually the first treatment option. Other drugs are as effective and have fewer side effects. However, sulfonylureas may be used as the first treatment for people who:2

  • Cannot take metformin
  • Have very high blood sugar (hyperglycemia)
  • Have a variety of T2D called maturity-onset diabetes of youth
  • Cannot afford other drugs


There are 2 generations of sulfonylureas. First-generation sulfonylureas have a higher risk of causing dangerously low blood sugar (hypoglycemia). They are not commonly used anymore. Examples of first-generation sulfonylureas include:1

  • Chlorpropamide (Diabinese®)
  • Tolazamide (Tolinase®)
  • Tolbutamide (Orinase®, Tol-Tab)

Second-generation sulfonylureas stay active in your body for a shorter time than first-generation sulfonylureas. This lowers the risk of hypoglycemia. Second-generation sulfonylureas are more commonly used. Examples include:1

  • Glimepiride (Amaryl®)
  • Glipizide/Glipizide XL (Glucotrol®, Glucotrol® XL)
  • Glibenclamide (Glynase® PresTab, Glynase®, Micronase®)

What are the possible side effects?

Side effects can vary depending on the specific drug you are taking. One common side effect of sulfonylureas is hypoglycemia. Hypoglycemia is most likely to occur:1,2

  • After exercise or a missed meal
  • In people with kidney or heart problems
  • When using certain other medicines
  • In people who have been drinking alcohol
  • In people taking longer-acting sulfonylureas, such as glyburide

Talk to your doctor about how to prevent and treat hypoglycemia. Some signs of hypoglycemia include:1

  • Sweating
  • Shaking
  • Irritability
  • Confusion
  • Fast heart rate
  • Feeling hungry

Other common side effects of sulfonylurea drugs include:1,2

  • Weight gain
  • Nausea
  • Skin reactions
  • Headache
  • Dizziness

These are not all the possible side effects of sulfonylureas. Talk to your doctor about what to expect when taking sulfonylureas. You also should call your doctor if you have any changes that concern you when taking sulfonylureas.

Other things to know

Use sulfonylureas exactly as your doctor describes. Your dose will depend on your health history, age, and other individual factors. Your doctor may change your dose over time. This will help manage glucose levels and lower the risk of side effects.1,2

Sulfonylureas should be combined with regular exercise and a healthy diet. Your doctor may suggest combining them with other T2D drugs, especially metformin. Do not stop taking any medicines without talking to your doctor.1

Before taking sulfonylureas, tell your doctor your full medical history. Other drugs or medical conditions may make sulfonylureas less safe. Talk to your doctor about:1,2

  • Any allergies, especially sulfa allergies
  • Any other medical conditions, especially chronic kidney disease
  • Any other medicine you take, including over-the-counter drugs, vitamins, and supplements
  • Pregnancy or plans to become pregnant

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