How Does Glipizide Work?

Published September 25th, 2020 by Chris Riley
Fact Checked by
Bridget Reed
Medically Reviewed:
Camille Freking
Updated Date: Apr 16th, 2021

The number of people diagnosed with diabetes has increased at an alarming rate over the past few decades. In fact, the American Diabetes Association has compared the growth rate of diabetes to an epidemic. Currently, 34.2 million Americans are diagnosed with the disease and a large percentage of people are estimated to be undiagnosed.  In many cases, the development of diabetes can be prevented by altering diet and making lifestyle changes like quitting smoking, getting more exercise and treating other conditions that may make you predisposed to diabetes, such as high blood pressure or cholesterol. However, diabetes also has a large genetic component to its cause, which can predispose individuals to the disease if there is a family history of it. 

The main feature of diabetes is a high blood sugar level that cannot be reduced through normal functioning of the body. There are two types of diabetes and both types are caused by a deficiency in the hormone, insulin, which moves sugar into cells to be converted into energy. In type 1 diabetes, the body cannot make insulin due to autoimmune reasons. In type 2 diabetes, insulin that is produced is ineffective due to insufficient quantity or inability to function properly. Both types of diabetes have no cure and must be treated to prevent other health risks from occurring. Untreated diabetes can lead to the following adverse conditions:

  • Blindness
  • Heart attack
  • Stroke
  • Kidney damage 
  • Nerve damage

Different medications are used to treat type 1 and type 2 diabetes. These medications have to be taken regularly and some of them must be taken life-long to manage the condition. Glipizide is one medication that is used to treat type 2 diabetes. Since a combination of medications is usually prescribed for the treatment of diabetes, it can be confusing to understand how they work in helping to treat the condition. Since diabetes drugs are one of the most commonly prescribed medications, we know a lot about how they work. 

What is Glipizide?

The average patient needs to ask their doctor: “What is Glipizide?” Glipizide is the generic name for the prescription brand names, Glucotrol and Glucotrol XL, made by the company Pfizer. This medication is used to achieve glycemic control in patients with type 2 diabetes as a second-line treatment method after metformin. Glipizide is not used on its own to treat type 1 diabetes. The medication has a very fast absorption rate and pharmacological data has shown that the drug has complete bioavailability after taking it. These features allow glipizide to start working faster compared to other diabetes medications in the same drug class. 

How does glipizide work?

According to the American Diabetes Association, there are nine different classes of diabetes drugs as treatment options to lower blood sugar. Drugs within each class work in a similar way and each class has many drug options. The major classes of drugs used to treat diabetes include alpha-glucosidase inhibitors, biguanides, bile acid sequestrants, dopamine-2 agonists, DPP-4 inhibitors, meglitinides, SGLT-2 inhibitors, sulfonylureas and thiazolidinediones (TZDs). Often, a combination of drugs from different classes is used together to achieve effective control of blood sugar in diabetic patients. 

The Sulfonylureas

Glipizide belongs to the class of drugs called the sulfonylureas. This class of drugs was discovered in the early 1940s by scientists studying the sulfonamide antibiotics. They observed that these antibiotics lowered blood sugar in animals that were given the drugs. The sulfonylurea drugs used in diabetes treatment were developed based on this discovery, and there are currently three generations of sulfonylurea drugs. Glipizide is a second-generation sulfonylurea medication along with other diabetes medications such as glyburide, gliclazide and glibornuride. The second-generation sulfonylureas were improved to have better potency. 

Glipizide is an ‘insulin secretagogue’ meaning that it stimulates the release of insulin from the beta islet cells of the pancreas where it is normally produced. This increases the amount of insulin that enters the blood, which can then lower blood glucose levels by transporting it to cells for energy conversion. The exact mechanism by which this happens involves a cascade of events. The sulfonylurea drugs bind to certain proteins on the beta-islet cells of the pancreas to reduce the passage of potassium ions in and out of the cells. This event causes opening of calcium channels within the cell, allowing calcium ions to enter. An increased concentration of calcium ions in the cell stimulates the secretion of insulin. This is the main mechanism through which glipizide works to lower blood glucose levels and its mode of action is dependent on the presence of functional beta-cells in the pancreas. Research has also suggested that glipizide, like other sulfonylureas, can also inhibit the secretion of the hormone glucagon, which normally raises the amount of glucose in the blood through its regulation of metabolic pathways. 

Additionally, glipizide exerts its ability to lower blood glucose in other ways that do not directly involve the pancreas. Research has found that the number of insulin receptors on different cell types, like fat cells and monocytes, are increased by the sulfonylurea drugs. It has also been found that glipizide can suppress glucose production in the liver, a biological process that normally contributes to blood sugar levels. This class of drugs also decreases the breakdown of fat in the liver. Overall, glipizide may also increase the body’s sensitivity to glucose intake and produce more insulin as a result. 

What to know when taking glipizide

Before taking glipizide, people with the following conditions should check with their doctor as taking the medication if you have ever had any of these conditions could be harmful. 

  • Diabetic ketoacidosis, a high level of ketones in the blood or urine, can occur in patients with both type 1 and type 2 diabetes that take glipizide. Glipizide is not indicated for the treatment of type 1 diabetes, but if you have type 2 diabetes and have ever had diabetic ketoacidosis, inform your doctor immediately. Taking glipizide could put you at increased risk for this condition, which can be fatal. 
  • Patients with chronic diarrhea or intestinal blockage should inform their doctor. 
  • People with a deficiency in the enzyme glucose-6-phosphate dehydrogenase (G6PD) should not take glipizide because it can cause hemolytic anemia in these individuals.

Glipizide should be taken exactly as prescribed by your doctor. Usually, this  this diabetes medication is taken once a day in the morning before the first meal of the day. The most common side effects that may occur when taking glipizide are digestive problems. These side effects include nausea, vomiting, diarrhea, constipation and headache. 

Hypoglycemia is also a serious side effect that is associated with taking glipizide. If you take other medications for diabetes that lower blood sugar, the risk of hypoglycemia is higher. It is important to recognize the signs of hypoglycemia like excessive sweating, hunger, headache, weakness, blurry vision and feeling dizzy. If hypoglycemia is not addressed immediately when symptoms begin, it can be dangerous. If you experience the symptoms of hypoglycemia while taking glipizide, you can drink or eat something with sugar in it such as candy or juice, but if symptoms persist, urgent medical attention is required.

Some commonly taken drugs, like the non-steroid anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen and aspirin can also cause low blood sugar to occur if they’re taken along with glipizide. Similarly, some blood pressure medication and blood thinners can also cause low blood sugar in combination with glipizide. Other medications may cause glipizide to be less effective and high blood sugar may result. Be sure to check with your doctor on whether any medications that you currently take could interfere with glipizide.

Pregnant women should also check with their doctor before taking glipizide. Usually, other classes of diabetes medications are preferred for women during pregnancy. 

How to buy glipizide

Glipizide is available as a generic medication or the brand name drugs, Glucotrol or Glucotrol XL. Glipizide is also available as a combination oral tablet with metformin, named metaglip. Metformin belongs to the biguanide class of diabetes drugs, so the combination of both drugs together can work in different ways to bring about an overall reduction in blood sugar levels. This is a good example of how medications from the different classes of drugs used to treat diabetes are used together.

By itself, generic glipizide is relatively inexpensive. This is good news for a second- line treatment drug used to treat diabetes, as many patients can afford to purchase their medication regularly. Even if you do not have health insurance, you can consider signing up for the convenient prescription drug discount card available from USA RX.  This card is completely free of cost and can help you get additional savings on glipizide, as well as any other FDA approved medications you may be taking for diabetes or other conditions. 

Keep in mind that medications used to treat diabetes are just one component of a treatment regimen of which dietary changes and exercise are also equally important to control the condition. By following the treatment method that is personally recommended for you, living with the diabetes can become less challenging. 




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