What is the difference between Glipizide (Glipizide) extended release (ER) and regular Glipizide (Glipizide)?

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Last updated: April 16, 2025View editorial policy

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From the Guidelines

Glipizide ER is generally preferred over regular glipizide for most patients due to its once-daily dosing and reduced risk of hypoglycemia, as supported by the most recent evidence from 2025 1.

Key Differences Between Glipizide ER and Regular Glipizide

  • Glipizide ER is taken once daily, typically 5-10mg each morning before breakfast, while regular glipizide requires twice-daily dosing, 2.5-5mg before breakfast and dinner.
  • The extended-release formulation provides more consistent blood glucose control throughout the day with fewer peaks and valleys in drug concentration, which may reduce the risk of hypoglycemia.
  • Glipizide ER works through a special delivery system that slowly releases the medication over 24 hours, while regular glipizide has a shorter duration of action of about 12-24 hours.

Considerations for Use

  • Both medications work by stimulating insulin release from the pancreas and should be taken with food to minimize stomach upset.
  • When switching between formulations, the same total daily dose is typically used, but patients should monitor blood glucose levels closely during the transition as individual responses may vary.
  • Neither formulation should be crushed or chewed, but regular glipizide tablets can be split if needed, while ER tablets should remain intact.

Evidence-Based Recommendations

  • The 2025 guidelines from the American Diabetes Association recommend using sulfonylureas with caution, especially in older adults, due to the risk of hypoglycemia and bone loss 1.
  • The 2018 consensus report by the American Diabetes Association and the European Association for the Study of Diabetes notes that glipizide, glimepiride, and gliclazide may have a lower risk of hypoglycemia compared to other sulfonylureas 1.
  • The 2009 consensus algorithm for the initiation and adjustment of therapy for type 2 diabetes recommends using second-generation sulfonylureas, such as glipizide, due to their lower risk of hypoglycemia compared to first-generation sulfonylureas like chlorpropamide and glibenclamide 1.

From the Research

Glipizide ER vs Regular Glipizide

  • The provided studies do not directly compare Glipizide ER and regular Glipizide, but they do offer information on the pharmacokinetics and efficacy of glipizide in general 2, 3.
  • Glipizide is well absorbed after oral administration, but its absorption is delayed by food 2.
  • The terminal elimination half-life of glipizide is 2-7 hours, which may support the use of an extended-release formulation to improve patient compliance and maintain therapeutic drug levels throughout the day 2.
  • In terms of efficacy, glipizide has been shown to be effective in controlling blood glucose levels in patients with type 2 diabetes mellitus, with some studies suggesting it may be more effective than other sulfonylureas such as glyburide 3.
  • However, the risk of serious hypoglycemia with glipizide is higher than with some other antidiabetic medications, such as metformin and pioglitazone 4.
  • The use of glipizide in combination with other antidiabetic medications, such as metformin and pioglitazone, may provide additional benefits in terms of glycemic control and improvement in insulin sensitivity and vascular function 5, 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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