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Glipizide vs. metformin: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Glipizide and metformin are two medications that are used to treat Type 2 diabetes mellitus. People with Type 2 diabetes have a problem with the hormone insulin, which is responsible for moving blood sugar (glucose) into the body’s cells for energy. When insulin doesn’t work as well, insulin resistance can develop and lead to increased glucose levels, which can then lead to other health problems. Glipizide and metformin can help manage high glucose levels to reduce the risk of complications from diabetes.

Compared to newer agents, glipizide and metformin are relatively inexpensive antidiabetic medications. They are both used for the long-term management of Type 2 diabetes. Even though they have similarities in overall effects, glipizide and metformin have several differences, especially in how they work, potential side effects, and drug interactions.

What are the main differences between glipizide and metformin?


Glipizide is the generic name for Glucotrol. It is part of a class of medications called sulfonylureas, and it works by stimulating the secretion of insulin from the pancreas. The increase in insulin helps lower blood glucose levels in the body.

Glipizide is available as a 5 mg or 10 mg oral tablet. Generic glipizide also comes in extended-release tablets in strengths of 2.5 mg, 5 mg, and 10 mg. Glipizide is usually taken once daily before breakfast.


Metformin is the generic name for Glucophage or Riomet, and it belongs to a class of drugs called biguanides. Metformin works to treat Type 2 diabetes by decreasing glucose production in the liver and decreasing the absorption of glucose in the intestines. It also works by increasing insulin sensitivity and increasing the uptake of glucose in the body’s tissues.

Metformin is available as an oral tablet in strengths of 500 mg, 850 mg, and 1000 mg. Extended-release metformin tablets are also available and designed to be taken once daily. Immediate-release metformin is often prescribed to be taken twice daily.

Main differences between glipizide and metformin
Glipizide Metformin
Drug class Sulfonylurea Biguanide
Brand/generic status Brand and generic version available Brand and generic version available
What is the brand name? Glucotrol Glucophage
What form(s) does the drug come in? Oral tablet Oral tablet
What is the standard dosage? 5 mg once daily before breakfast. Dosage may be adjusted according to response and medical condition. Maximum dose of 40 mg per day. 500 mg twice daily or 850 mg once daily with meals. Dosage may be adjusted according to response and medical condition. Maximum dose of 2,550 mg per day.
How long is the typical treatment? Long-term for diabetes management Long-term for diabetes management
Who typically uses the medication? Adults aged 18 years and older Adults and children aged 10 years and older 

Conditions treated by glipizide and metformin

Glipizide and metformin are both FDA-approved to treat Type 2 diabetes mellitus. Controlling high blood sugar levels can help decrease the risk of complications from diabetes. These complications may include heart disease, kidney disease, liver disease, eye damage, and foot infections.

Metformin is sometimes used off-label to treat other conditions, such as gestational diabetes, or diabetes during pregnancy, and polycystic ovary syndrome (PCOS). Metformin is also used off-label to treat weight gain that’s caused as a side effect of certain antipsychotic medications.

No significant studies have been conducted on the off-label uses of glipizide.

Condition Glipizide Metformin
Type 2 diabetes mellitus Yes Yes
Gestational diabetes No Off-label
Polycystic ovary syndrome No Off-label
Weight gain due to antipsychotic therapy No Off-label

Is glipizide or metformin more effective?

Glipizide and metformin are both effective diabetes medications to improve glycemic control in people with Type 2 diabetes. They can be used as monotherapy or as a combination pill called Metaglip. Glipizide and metformin work best when used with a proper diet and exercise regimen.

Metformin remains the first-line therapy for Type 2 diabetes, according to guidelines from the American Diabetes Association (ADA). When compared for effectiveness in those with Type 2 diabetes and coronary artery disease, metformin reduces the risk of heart attack and stroke more than glipizide. According to a double-blind, clinical trial, metformin showed a greater cardioprotective effect than glipizide after a period of five years.

Another comparative trial found that metformin provided better blood sugar control than glipizide. Those taking metformin in the study had better fasting plasma glucose levels than glipizide after 24, 36, and 52 weeks. Those taking metformin also had a lower HbA1c level than those taking glipizide after 52 weeks. Metformin caused weight loss and glipizide caused weight gain in treated participants.

Consult a healthcare provider for medical advice on the best treatment for you if you have Type 2 diabetes. Depending on your overall medical condition, blood sugar levels, and other medications you may be taking, one drug may be preferred over the other.

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Coverage and cost comparison of glipizide vs. metformin

Glipizide is a generic antidiabetic medication that is usually covered by Medicare and insurance plans. For a standard supply of glipizide, the copay can range from $0 to $9. The average retail price of glipizide can be around $30. A SingleCare glipizide coupon can help lower the cost to $4 at participating pharmacies.

Metformin is a commonly prescribed antidiabetic drug that is covered by most Medicare and insurance plans. The typical Medicare copay can range from $0 to $8, and the retail price can be around $25 depending on the pharmacy you go to. A metformin coupon from SingleCare may reduce the price to as low as $4.

  Glipizide Metformin
Typically covered by insurance? Yes Yes
Typically covered by Medicare Part D? Yes Yes
Standard dosage 5 mg once daily (quantity of 60 tablets) 500 mg twice daily (quantity of 60 tablets)
Typical Medicare copay $0–$9 $0–$8
SingleCare cost $4+ $4+

Common side effects of glipizide vs. metformin

The most common side effects of glipizide include low blood sugar (hypoglycemia), constipation, diarrhea, nausea, and dizziness.

The most common side effects of metformin include diarrhea, nausea, weakness (asthenia), hypoglycemia, and headache.

Serious side effects of glipizide include severe hypoglycemia and hemolytic anemia. Serious side effects of metformin include lactic acidosis and vitamin B12 deficiency. Consult a healthcare provider for other potential side effects of glipizide or metformin.

  Glipizide Metformin
Side effect Applicable? Frequency Applicable? Frequency
Hypoglycemia Yes * Yes 1%–5%
Constipation Yes * No
Diarrhea Yes * Yes 53%
Nausea Yes * Yes 26%
Dizziness Yes * No
Weakness No Yes 9%
Headache Yes * Yes 6%

*not reported
Frequency is not based on data from a head-to-head trial. This may not be a complete list of adverse effects that can occur. Please refer to your doctor or healthcare provider to learn more.
Source: DailyMed (Glipizide), DailyMed (Metformin)

Drug interactions of glipizide vs. metformin

Glipizide and metformin can interact with similar medications. Certain drugs can increase the blood sugar lowering effects of glipizide and metformin, which can increase the risk of hypoglycemia. These drugs include other antidiabetic drugs and certain blood pressure lowering agents like ACE inhibitors and angiotensin type II receptor blockers.

Some drugs can decrease how well glipizide and metformin work, which can reduce their blood sugar lowering effects. These drugs may include calcium channel blockers, diuretics, corticosteroids, beta blockers, and oral contraceptives. The signs of hypoglycemia can be masked while taking beta blockers, so they should be monitored in people taking these medications.

Metformin can also interact with carbonic anhydrase inhibitors, like topiramate and zonisamide, which can increase the risk of lactic acidosis. Other drugs such as ranolazine and vandetanib can interact with metformin and interfere with its elimination from the kidneys. These drugs can increase the levels of metformin in the blood and increase the risk of lactic acidosis.

Drug Drug class Glipizide Metformin
Carbonic anhydrase inhibitors No Yes
Ranolazine Antianginals No Yes
Vandetanib Tyrosine kinase inhibitors No Yes
Antidiabetic agents Yes Yes
ACE inhibitors Yes Yes
Angiotensin II receptor blocking agents Yes Yes
Calcium channel blockers Yes Yes
Corticosteroids Yes Yes
Diuretics Yes Yes
Beta blockers Yes Yes
Conjugated estrogens
Ethinyl estradiol
Estrogens and oral contraceptives Yes Yes

Consult a healthcare professional for other possible drug interactions

Warnings of glipizide and metformin

Because of their glucose-lowering effects, glipizide and metformin carry a risk of hypoglycemia, or low blood sugar levels. The risk of hypoglycemia is increased when glipizide or metformin is taken with other antidiabetic agents. Prolonged exercise and alcohol consumption may also increase this risk. Symptoms of hypoglycemia include nervousness, sweating, fast heartbeat, and confusion.

Certain people with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk of developing hemolytic anemia while taking glipizide. However, some people without GP6D deficiency can also develop hemolytic anemia.

The use of metformin can lead to metformin-associated lactic acidosis. This type of lactic acidosis is usually associated with an overdose of metformin. However, there is also a risk of lactic acidosis in people with decreased liver or kidney functions. Signs and symptoms of lactic acidosis include nausea, low blood pressure, and abdominal pain.

Consult a healthcare provider for other possible warnings and precautions associated with glipizide or metformin.

Frequently asked questions about glipizide vs. metformin

What is glipizide?

Glipizide is a generic medication that belongs to a class of drugs called sulfonylureas. The brand name of glipizide is Glucotrol. Glipizide works by increasing the release of insulin from the pancreas to lower blood sugar levels. It is available as an immediate-release and extended-release oral tablet.

What is metformin?

Metformin is also known by common brand names such as Riomet and Glucophage. It belongs to a class of antidiabetic drugs called biguanides. Metformin works by increasing insulin sensitivity, decreasing glucose production in the liver, and decreasing intestinal absorption of glucose. Metformin is available as an immediate-release and extended-release oral tablet.

Are glipizide and metformin the same?

Glipizide and metformin are not the same. Glipizide is a sulfonylurea that treats Type 2 diabetes in adults and metformin is a biguanide that treats Type 2 diabetes in adults and children who are 10 years of age and older. Glipizide and metformin work in different ways and have different dosages.

Is glipizide or metformin better?

Glipizide and metformin both work to lower blood glucose levels in those with Type 2 diabetes. According to the American Diabetes Foundation guidelines, metformin is the first-line therapy for Type 2 diabetes. Glipizide and metformin may sometimes be taken together in some cases where a greater glucose-lowering effect is needed. Overall, the best diabetes medicine depends on your overall medical condition and response to the drug.

Can I use glipizide or metformin while pregnant?

Compared to metformin, glipizide may have a higher potential to cause fetal toxicity. According to animal studies, metformin may be safe for use during pregnancy; but no conclusive studies in humans have been conducted. Consult a healthcare provider to determine the best treatment option for you while pregnant.

Can I use glipizide or metformin with alcohol?

It is not recommended to consume excessive amounts of alcohol while taking glipizide or metformin. Drinking alcohol can cause unpredictable blood sugar levels and increase the risk of hypoglycemia or hyperglycemia. Alcohol may also increase the risk of lactic acidosis while on metformin.

What is the best time of day to take glipizide?

The best time to take glipizide is before meals in order to reduce the risk of hypoglycemia. If it’s being taken once per day, glipizide is recommended to be taken before the first meal of the day.

Is glipizide bad for the kidneys?

Uncontrolled Type 2 diabetes may lead to complications like kidney damage. However, glipizide is not known to cause damage to the kidneys. The elimination of glipizide can be slowed in people with kidney damage. An accumulation of glipizide can then lead to an increased risk of low blood sugar levels.

What is the safest drug for Type 2 diabetes?

Metformin is usually prescribed as a first-line therapy for Type 2 diabetes in most people. That’s because metformin is relatively inexpensive, safe, and effective. Compared to other antidiabetic agents, metformin is linked to lower or similar HbA1c levels. The use of metformin is also associated with lower incidences of hypoglycemia than other drugs like sulfonylureas.