From the Guidelines
Metformin is the most commonly paired medication with glipizide for diabetes management, as it has complementary mechanisms of action and is recommended by recent guidelines 1. When considering combination therapy with glipizide, it's essential to choose medications that have different mechanisms of action to achieve optimal glucose control.
- Metformin reduces glucose production by the liver and improves insulin sensitivity, making it an ideal combination with glipizide, which stimulates insulin release from the pancreas.
- Other medications that pair well with glipizide include DPP-4 inhibitors (like sitagliptin), GLP-1 receptor agonists (like semaglutide), and SGLT-2 inhibitors (like empagliflozin), each offering different complementary mechanisms.
- The choice of medication added to glipizide should be based on the patient's clinical characteristics, disease, drug characteristics, and patient preferences, as recommended by the American Diabetes Association standards of care in diabetes-2023 1.
- When combining medications, it's crucial to monitor for hypoglycemia, especially when first starting the combination therapy, as glipizide can cause low blood sugar, particularly if meals are skipped or during increased physical activity.
- Recent studies, such as the VERIFY trial, have shown that initial combination therapy can provide a lower rate of secondary failure of glycemic control, supporting the use of combination therapy in certain patients 1.
- The most recent guidelines from 2025 suggest that initial combination therapy should be considered in people presenting with type 2 diabetes, and that the choice of medication added to metformin or glipizide should be based on the patient's clinical characteristics and preferences 1.
From the FDA Drug Label
Co-administration of ACTOS and 5 mg glipizide administered orally once daily for 7 days did not alter the steady-state pharmacokinetics of glipizide.
The diabetic medications that are paired well with Glipizide are:
- Metformin: as shown in the study where VICTOZA was used as add-on to metformin and glimepiride, or metformin and sulfonylurea.
- Pioglitazone (ACTOS): as the drug label states that co-administration of ACTOS and glipizide did not alter the steady-state pharmacokinetics of glipizide 2.
- Insulin: as shown in the study where VICTOZA was used as add-on to metformin and glimepiride, or insulin glargine was used as add-on to metformin and glimepiride. Note that Glimepiride is also a sulfonylurea, similar to Glipizide.
From the Research
Diabetic Medications Paired with Glipizide
- Metformin: Studies have shown that combining glipizide with metformin can be an effective treatment for type 2 diabetes, as it addresses both insulin resistance and impaired insulin secretion 3.
- Pioglitazone: Although there is no direct evidence of glipizide being paired with pioglitazone, studies have shown that pioglitazone can be combined with other medications, such as metformin and sitagliptin, to improve glycemic control 4, 5, 6.
- Sitagliptin: Sitagliptin has been shown to be as effective as glipizide in reducing A1c levels, and has a lower risk of hypoglycemia 7. However, there is no direct evidence of glipizide being paired with sitagliptin.
Combination Therapies
- Glipizide/Metformin: This combination has been shown to be more effective than either glipizide or metformin monotherapy in controlling HbA1c levels and reducing fasting plasma glucose 3.
- Pioglitazone/Metformin: This combination has been shown to be effective in improving glycemic control and reducing cardiovascular risk factors 4, 6.
- Sitagliptin/Pioglitazone: This combination has been shown to be effective in improving glycemic control and reducing HbA1c levels 5, 7.