Glipizide vs. Glyburide: 7 Ways These Sulfonylureas Compare for Type 2 Diabetes

Over the last two decades, the treatment landscape for Type 2 diabetes has expanded significantly, offering many newer options. Despite this, older oral medications, such as glipizide (Glucotrol XL) and glyburide (DiaBeta, Glynase) remain viable choices for managing blood glucose (sugar) in certain people.

Glipizide and glyburide are in the same medication class. But they have important differences to consider. These include their formulations, when you take them, and side effect risks. Below, we explore seven key ways glipizide and glyburide compare.

1. Glipizide and glyburide work in a similar way

Glipizide and glyburide belong to a group of medications called sulfonylureas. They both work by stimulating the pancreas to release more insulin — a hormone that helps cells absorb and use glucose from the blood. They also slow the clearance of insulin in the liver, keeping it around for longer.

Glipizide and glyburide work similarly well to lower blood glucose levels. In general, sulfonylureas lower hemoglobin A1C — a marker of average blood glucose levels over 3 months — by about 1% to 1.25%.

2. Glipizide and glyburide come in different formulations

A key difference between glipizide and glyburide is their available formulations, which can affect their dosage and how they’re absorbed in the body.

Glipizide is available in immediate-release (IR) and extended-release (ER) tablets. The IR tablets are taken once or twice a day. The ER tablets release the medication more slowly, so they’re taken once a day. Glyburide is available as an IR tablet in two forms: micronized (Glynase) and nonmicronized (DiaBeta). Both forms work similarly well and are taken once or twice daily. 

EXPERT PICKS: WHAT TO READ NEXT

• Glipizide side effects: Do you feel dizzy after taking glipizide? Here’s a list of glipizide side effects and tips for managing them.

• Know your options: Explore oral medication options for Type 2 diabetes and how they compare. 

• Sulfonylureas 101: Glipizide and glyburide are both sulfonylurea medications. Learn more about sulfonylureas — how they work, their availability, and more.

The micronized version of glyburide contains smaller particles, which are absorbed more quickly than the nonmicronized form. Because of this, they aren’t directly interchangeable at the same dose. If you switch between the two, your prescriber may need to adjust your dose.

3. Glipizide and glyburide are timed differently around meals

Both glipizide and glyburide doses are timed around meals to maximize their effectiveness and reduce the risk of hypoglycemia (low blood glucose). But there are some differences in how and when they should be taken:

• Glipizide IR: Take 30 minutes before breakfast (or first main meal). If you take a second dose, take it 30 minutes before your last meal of the day. Glipizide IR starts working within 30 minutes, so this allows it to kick in just as your blood glucose begins to rise. Conversely, taking your dose with food can slow its absorption, delaying its effects.

• Glipizide ER: Take with your first meal of the day. The ER tablets release the medication gradually over time, so food doesn’t significantly affect how they work.

• Glyburide (micronized and nonmicronized): Take with a meal, regardless of the formulation. For a once-daily dosage, take your dose with breakfast or the first main meal of the day. For a twice-daily dosage, take your second dose with your last meal.

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Sulfonylureas such as glipizide and glyburide cause insulin release without regard to food. So timing your doses around meals this way ensures you have enough glucose present to balance out the insulin-releasing effects. Otherwise, your blood glucose levels could drop too low, causing hypoglycemia symptoms, such as dizziness, sweating, and a fast heart rate.

4. Glipizide starts working faster than glyburide

When it comes to lowering blood glucose, glipizide generally acts faster than glyburide. Glipizide IR tablets start working within 30 minutes. In contrast, glyburide can take up to an hour to start lowering blood glucose. Glipizide ER tablets act more gradually — usually within a few hours.

Both micronized and nonmicronized forms of glyburide start working within an hour. But the micronized form is absorbed faster and more efficiently because of its smaller particle size.

5. Glipizide may be preferred for older adults and people with kidney problems

Glipizide IR is generally preferred over glyburide for people at higher risk of hypoglycemia, such as older adults and those with kidney problems. This is because of its shorter duration of action and how it’s broken down and cleared from the body.

Both medications are broken down in the liver, with a certain amount removed from the body by the kidneys. Glipizide is primarily broken down into inactive substances. Glyburide, on the other hand, produces active substances. These active substances can build up in people with kidney problems. This can increase the risk of hypoglycemia, especially in people at greater risk.

Discuss your full medical history with your healthcare professional. They can help you choose the safest treatment option, especially if hypoglycemia is a concern. If they prescribe glipizide for you, they may start with a lower dose to decrease this risk. There are also several other diabetes medications with a low hypoglycemia risk to choose from.

6. Glipizide and glyburide can cause similar side effects

Since glipizide and glyburide belong to the same medication class, they can cause similar side effects. The most common side effect is hypoglycemia, especially if doses aren’t timed around meals. They also have similar interactions that can increase the risk of hypoglycemia. 

Other common side effects include:

• Nausea

• Heartburn

• Weight gain

• Rash

• Liver test changes

Glipizide and glyburide may cause other side effects, too. Discuss what you should watch out for with your healthcare team.

7. Glyburide might be more likely to cause hypoglycemia

Hypoglycemia is possible with glipizide and glyburide. But studies suggest that the risk may be higher with glyburide.

A 2007 systematic review and meta-analysis found that people taking glyburide had a 52% higher risk of hypoglycemia than those taking other diabetes medications and an 83% higher risk than those taking other sulfonylureas, including glipizide. Glyburide’s long duration of action means that it continues lowering blood glucose throughout the day. And it produces active substances that can build up in certain people, too.

When left untreated, hypoglycemia can be life-threatening. Talk to your prescriber about the signs and symptoms of hypoglycemia. Educate family and friends so they can also be aware, in case you should experience hypoglycemia when you’re with them. Be sure to have a plan in place in case your blood glucose drops too low. If you notice symptoms such as dizziness, sweating, and shakiness, check your glucose levels right away.

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Written by:

Kristianne Hannemann, PharmD

Kristianne Hannemann, PharmD, is a licensed pharmacist in California. She has been a retail pharmacy manager and staff pharmacist for over 7 years and has contributed drug information content to different health companies.

Edited by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

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