From the Guidelines
Glipizide and metformin are two distinct oral medications for type 2 diabetes with different mechanisms of action, and metformin is generally preferred as first-line therapy due to its beneficial effects on insulin resistance, weight, and cardiovascular mortality, as well as its lower risk of hypoglycemia 1.
Mechanism of Action
- Glipizide is a sulfonylurea that stimulates the pancreas to release more insulin, making it effective only when the pancreas can still produce insulin.
- Metformin is a biguanide that works by reducing glucose production in the liver, improving insulin sensitivity in muscles, and decreasing intestinal absorption of glucose.
Key Differences
- Glipizide works quickly to lower blood sugar and is typically taken once or twice daily before meals, with dosages ranging from 5-40mg per day.
- Metformin doesn't cause hypoglycemia when used alone and often leads to modest weight loss, and is typically taken with meals, starting at 500mg once or twice daily and potentially increasing to 2000-2500mg daily.
Side Effects and Contraindications
- Glipizide may cause hypoglycemia (low blood sugar) and weight gain.
- Metformin may cause gastrointestinal side effects like diarrhea and can't be used in patients with severe kidney disease, and is associated with an increased risk of vitamin B12 deficiency and worsening of symptoms of neuropathy 1.
Clinical Recommendations
- Metformin is the preferred initial pharmacological agent for type 2 diabetes, unless contraindicated or not tolerated, due to its efficacy, safety, and potential cardiovascular benefits 1.
- Glipizide may be considered as an alternative or add-on therapy in certain cases, but its use should be carefully weighed against its potential risks and benefits.
From the FDA Drug Label
Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization The primary mode of action of glipizide in experimental animals appears to be the stimulation of insulin secretion from the beta cells of pancreatic islet tissue and is thus dependent on functioning beta cells in the pancreatic islets
The main difference between glipizide and metformin in terms of mechanism of action is:
- Glipizide stimulates insulin secretion from the beta cells of pancreatic islet tissue, increasing insulin levels in response to a meal.
- Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity without increasing insulin secretion. 2 3
From the Research
Mechanism of Action
The primary mechanism of action of glipizide and metformin differs:
- Glipizide, a sulfonylurea, works by stimulating the release of insulin from the pancreatic beta cells, thereby increasing insulin secretion and reducing blood glucose levels 4, 5, 6.
- Metformin, on the other hand, decreases hepatic glucose production, increases insulin sensitivity, and enhances glucose uptake by muscles, thereby reducing blood glucose levels without increasing insulin secretion 4, 6.
Comparison of Effects
Studies have compared the effects of glipizide and metformin on glucose control:
- A study found that glipizide/metformin combination tablets controlled HbA1c levels more effectively than either glipizide or metformin monotherapies 4.
- Another study showed that the addition of glipizide to metformin significantly improved glucose control in patients with type 2 diabetes inadequately controlled by metformin monotherapy 5.
- A comparative trial found that metformin gave better fasting plasma glucose control and resulted in weight loss, whereas glipizide treated subjects gained weight 6.
Safety and Efficacy
The safety and efficacy of glipizide and metformin as second-line therapies in type 2 diabetes mellitus have been compared:
- A systematic review found that sulfonylureas, such as glipizide, are more efficacious in lowering HbA1c, but have a higher risk of hypoglycemic events compared to DPP-4 inhibitors 7.
- The review also suggested that DPP-4 inhibitors may be considered a clinically stable choice for second-line therapy after completing maximally tolerated doses of metformin, despite the higher efficacious characteristics of sulfonylureas 7.