8 Glyburide Side Effects and How to Manage Them

If you’ve been prescribed glyburide (Diabeta, Glynase), it can be a valuable tool in your diabetes management. But along with the medication’s benefits for your blood glucose (sugar) levels, it’s good to be aware of potential side effects that may happen while taking it.

Many glyburide side effects can be managed at home with a few dietary and lifestyle changes. And if needed, over-the-counter (OTC) remedies can help manage specific symptoms. While more serious side effects are also possible, they tend to be rare. Here’s what you should know.

Glyburide side effects at a glance

Similar to other sulfonylurea medications, glyburide can cause side effects. Most glyburide side effects are mild and may go away over time as your body gets used to the medication or after your dose is lowered. However, certain side effects may require medical attention.

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Mild glyburide side effects include:

• Nausea

• Hypoglycemia (low blood glucose)

• Heartburn

• Epigastric fullness (feeling of a full stomach)

• Itching or rash

• Weight gain

• Sun sensitivity

Less common but potentially severe glyburide side effects include:

• Severe hypoglycemia

• Hemolytic anemia

• Blood disorders, such as low white blood cells or platelets

• Liver damage

• Allergic reactions, such as angioedema (swelling of the mouth or tongue)

• Vasculitis (blood vessel swelling)

Below, we cover eight glyburide side effects, including tips for managing them and when to contact your prescriber.

1. Nausea

You may experience nausea or an upset stomach while taking glyburide. While it’s one of the most common glyburide side effects, nausea was reported by less than 2% of people taking the medication during clinical trials. So it’s still fairly uncommon.

Nausea from glyburide tends to be more likely after your dose is increased. And it may lessen over time as your body gets used to the medication. But for initial relief, eating bland foods and drinking plenty of fluids may help. Instead of large meals, try eating smaller meals spaced throughout the day to lessen your upset stomach.

If these dietary changes aren’t doing the trick, consider ginger, peppermint, or an OTC (over-the-counter) medication if your nausea continues.

Contact your prescriber if your nausea is persistent or getting worse. They may try lowering your dose to see if that helps. Severe nausea with other symptoms, such as abdominal pain and dark urine, could indicate liver damage. More on that later.

2. Heartburn

Heartburn is possible while taking glyburide, especially after your dose is increased. Since heartburn can have many causes, it may help to take note of when your symptoms started and if anything makes them better or worse. For example, did you have heartburn when you first started glyburide? Or did you notice a change after your glyburide dose was increased?

Glyburide is usually taken with breakfast or your first main meal of the day. Be sure to take your dose with a full glass of water and remain upright for 2 to 3 hours after taking it. Lying down with a full stomach may worsen heartburn.

You may also notice that certain foods or drinks contribute to your symptoms. Common breakfast beverages, such as coffee and orange juice, are typical culprits. Spicy, greasy, and fatty foods can also make heartburn worse.

For occasional heartburn, OTC antacids, such as Tums, may help you feel better. But if your heartburn persists, contact your prescriber. Depending on your symptom triggers and timing, they may try lowering your glyburide dose.

3. Hypoglycemia

Hypoglycemia is possible while taking sulfonylureas, including glyburide. While hypoglycemia is possible if you take glyburide on its own, this risk goes up when it’s taken with other diabetes medications. Examples of these include metformin and insulin.

People can experience hypoglycemia differently. But if it happens to you, some common symptoms to watch out for include:

• Hunger

• Thirst

• Confusion

• Fast heartbeat

• Anxiety

• Weakness

• Shakiness

• Drowsiness

If you think your blood glucose might be too low, check your levels using your blood glucose monitor. If they’re below 70 mg/dL, consume 15 g of fast-acting carbohydrates, such as 4 glucose tablets or a half cup of juice. Wait 15 minutes, then recheck your blood glucose. Repeat this process until your reading is above 70 mg/dL.

A blood glucose level below 55 mg/dL is considered severe hypoglycemia. A friend or family member should administer glucagon, if it’s available, and call 911.

Talk to your prescriber if you’re experiencing frequent hypoglycemic episodes with glyburide. This could be a sign that your diabetes regimen needs to be adjusted.

Good to know: Compared to other sulfonylureas, glyburide lasts longer in the body. This can be risky for people at higher risk of severe hypoglycemia, such as older adults and people with kidney problems. In this case, a shorter-acting sulfonylurea, such as immediate-release glipizide, may be preferred.

4. Weight gain

Glyburide is one of several diabetes medications that can cause weight gain. The average amount of weight that people gain with sulfonylureas, such as glyburide, is 5 lbs over several months.

If you’re concerned about weight gain after starting glyburide, your healthcare team can help you create a weight management plan that works for your lifestyle. This may include slowly incorporating regular exercise and dietary changes into your routine.

As you start to make some of these changes, it’s a good idea to monitor your blood glucose closely. Certain factors, such as increased physical activity, can raise the risk of hypoglycemia if you don’t fuel up properly.

If needed, your prescriber may recommend an alternative or additional diabetes medication that can cause weight loss, such as Ozempic (semaglutide) or Mounjaro (tirzepatide).

5. Allergic skin reactions

Allergic skin reactions such as itching, swelling, or rash may occur with glyburide. Skin reactions may happen briefly after starting glyburide and tend to go away with continued use.

Although you might be tempted, avoid scratching the affected skin since this can worsen the irritation. Instead, a cold compress is an easy way to help to bring down any inflammation. You can also try applying an OTC topical steroid or taking an antihistamine, such as diphenhydramine (Benadryl).

Contact your prescriber if you have a persistent rash that isn’t resolved by OTC treatments. Call 911 or have someone take you to the nearest ER if your rash is accompanied by swelling of the face, lips, tongue, or throat. Report skin peeling to your healthcare team immediately.

6. Sun sensitivity

Glyburide may make your skin more sensitive to the sun. For example, you may develop a rash or bumps after spending time outdoors. You may also find that you’re more likely to get a sunburn.

Be sure to protect your skin with sunscreen before sun exposure, and wear a hat, sunglasses, or clothes that block UV rays. If you develop a rash or burn from sunlight, it may help to apply a cool compress to the affected skin. Topical anti-itch creams, antihistamines, and pain relievers can also relieve symptoms.

Most mild symptoms of sun sensitivity or sunburn can be treated at home. If you experience severe blistering, dehydration with nausea, or confusion, seek medical attention.

7. Liver damage

Glyburide may cause an increase in liver enzymes, which can be a sign of inflammation or damage. For most people, this doesn’t usually cause noticeable symptoms. But in rare cases, severe liver damage is possible. In this case, symptoms tend to develop within 1 to 3 months of starting glyburide. Common symptoms include:

• Tiredness

• Nausea

• Right upper abdomen pain

• Decreased appetite

• Yellowing of the skin or eyes (jaundice)

• Dark urine

Your healthcare team may test your liver enzymes during treatment to see if they’re high. If needed, they may have you stop glyburide to allow your liver to recover. But you should tell them right away if you develop any symptoms listed above.

Liver damage from glyburide may be more likely if you take it with other medications that are hard on your liver. Make sure your healthcare team has your current medication list while taking glyburide. It’s a good idea to check with them before taking anything new.

8. Blood disorders

There have been reports of certain blood disorders in some people taking glyburide. Examples of these include low white blood cell count (leukopenia) and low platelets (thrombocytopenia). People with an inherited condition called glucose 6-phosphate dehydrogenase (G6PD) deficiency may have a risk of hemolytic anemia, which results in low red blood cells.

These disorders involve blood cells that help fight off infections, cause your blood to clot, or carry oxygen to your tissues. If these cell counts are lower than normal, you may have symptoms such as fatigue, jaundice, or increased bleeding and bruising. You may also be more prone to infections.

You may not realize that your blood cell counts are low. In this case, your healthcare team may notice it on your routine blood work. But you should tell them if you notice any new or worsening symptoms after starting glyburide. And if you know that you have a G6PD deficiency, make sure they’re aware before starting treatment. It’s possible they’ll want you to avoid sulfonylureas like glyburide.

When should you contact your prescriber about glyburide side effects?

If you have questions or concerns about glyburide side effects, reach out to your prescriber. They can help you determine whether the symptoms you’re experiencing are from glyburide or something else. Depending on the cause, your prescriber may suggest dosage adjustments, lifestyle changes, or OTC medications to help manage or resolve the issue.

Try keeping detailed notes on when your side effects occur and how severe they are. This information can help your healthcare team pinpoint the cause and determine the best next steps. It can also help you identify potential contributing factors, such as foods or beverages, that worsen or alleviate your symptoms.

Certain glyburide side effects require immediate medical attention. Examples include severe hypoglycemia, allergic reactions (such as swelling of the face, lips, or throat), and symptoms of liver damage.

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Written by:

Stacey McCoy, PharmD, MS, BCPS

Stacey McCoy is a clinical pharmacy specialist with over 20 years of experience in various practice areas, including nearly 13 years as an emergency medicine specialist.

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:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

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