From the Guidelines
Metformin is the most effective medication to use in combination with glipizide for glycemic control, as it provides complementary mechanisms of action and has been shown to reduce the risk of cardiovascular events and death 1.
Key Considerations
- The combination of metformin and glipizide allows for a clearer assessment of the positive and negative effects of new drugs and reduces patient risk and expense.
- Metformin reduces insulin resistance and decreases glucose production by the liver, while glipizide stimulates insulin release from the pancreas.
- The American Diabetes Association/European Association for the Study of Diabetes consensus report recommends a patient-centered approach to choosing appropriate pharmacologic treatment of blood glucose, considering factors such as efficacy, comorbidities, hypoglycemia risk, effects on body weight, side effects, cost, and patient preferences 1.
Dosage and Administration
- Metformin is typically started at 500mg once or twice daily with meals, gradually increasing to 1000mg twice daily as tolerated.
- Glipizide is usually started at 5-10mg daily, taken before breakfast or split between morning and evening meals.
Potential Side Effects
- Hypoglycemia, especially when skipping meals
- Gastrointestinal issues like diarrhea or nausea, more common with metformin
- Rare but serious lactic acidosis with metformin
Monitoring and Follow-up
- Regular blood glucose monitoring is essential when using this combination to ensure optimal dosing and effectiveness.
- Patients should be closely monitored for potential side effects and adjusted as needed.
Additional Considerations
- The VERIFY trial demonstrated that initial combination therapy with metformin and a DPP-4 inhibitor is superior to sequential addition of medications for extending primary and secondary failure 1.
- The 2020 KDIGO clinical practice guideline recommends using metformin and an SGLT2 inhibitor as first-line treatment for patients with type 2 diabetes and CKD, with additional drug therapy as needed for glycemic control 1.
From the FDA Drug Label
The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, quinolones and beta adrenergic blocking agents Certain drugs tend to produce hyperglycemia and may lead to loss of control These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid.
The most effective medications in combination with glipizide for glycemic control are not explicitly stated in the label. However, it can be inferred that medications that do not potentiate hypoglycemia or produce hyperglycemia may be safer to use in combination with glipizide.
- Medications to use with caution in combination with glipizide include:
- Nonsteroidal anti-inflammatory agents
- Azoles
- Salicylates
- Sulfonamides
- Chloramphenicol
- Probenecid
- Coumarins
- Monoamine oxidase inhibitors
- Quinolones
- Beta adrenergic blocking agents
- Medications that may lead to loss of control when used in combination with glipizide include:
- Thiazides and other diuretics
- Corticosteroids
- Phenothiazines
- Thyroid products
- Estrogens
- Oral contraceptives
- Phenytoin
- Nicotinic acid
- Sympathomimetics
- Calcium channel blocking drugs
- Isoniazid 2
From the Research
Medications Effective in Combination with Glipizide for Glycemic Control
- Metformin is a biguanide that decreases blood glucose concentration by enhancing insulin sensitivity, inducing greater peripheral uptake of glucose, and decreasing hepatic glucose output 3, 4.
- The combination of metformin and sulfonylurea (such as glipizide) significantly improves glycemic control beyond that achieved with either agent alone 3.
- SGLT2 inhibitors, such as canagliflozin, dapagliflozin, and empagliflozin, can be used in combination with metformin to improve glycemic control, but may increase the risk of metabolic acidosis 5, 6.
- Glimepiride and metformin fixed-dose combinations are widely used in the management of type 2 diabetes mellitus (T2DM) patients with comorbidities and complications, and are suitable for early as well as long-standing diabetes 7.
Key Considerations
- Metformin is generally well-tolerated, but may cause gastrointestinal side effects and has a minimal risk of lactic acidosis 3, 4.
- SGLT2 inhibitors may cause euglycemic diabetic ketoacidosis and increase the risk of metabolic acidosis when used in combination with metformin 5, 6.
- Glimepiride and metformin combinations are effective in managing T2DM patients with comorbidities like hypertension, dyslipidemia, and diabetes complications 7.