Saxagliptin

Primary Use

Saxagliptin is primarily used to manage blood glucose (sugar) levels in adults with type 2 diabetes mellitus. It belongs to a class of drugs known as dipeptidyl peptidase-4 (DPP-4) inhibitors. By helping the body increase the amount of insulin released after meals and decreasing the amount of sugar made by the liver, it helps keep blood sugar within a healthy range.

Treatment Approach

This medication is intended to be used as part of a comprehensive treatment plan that includes:

• A healthy diet
• Regular physical activity
• Weight management

Saxagliptin may be used alone or in combination with other diabetes medications, such as metformin, sulfonylureas, or insulin, to achieve better blood sugar control.

Limitations of Use

Saxagliptin is not used to treat type 1 diabetes, a condition where the body does not produce insulin. It is also not used for the treatment of diabetic ketoacidosis, which is a serious complication of diabetes involving high levels of blood acids called ketones.

How Saxagliptin Works

Saxagliptin belongs to a class of medications known as dipeptidyl peptidase-4 (DPP-4) inhibitors. It works by blocking the action of the DPP-4 enzyme, which normally breaks down hormones in the body called incretins.

Incretin hormones are released by the intestines throughout the day, and their levels increase significantly after a meal. These hormones help the body manage blood sugar in two main ways:

• Stimulating Insulin Release: Incretins signal the pancreas to produce and release more insulin when blood sugar levels are high. Insulin is the hormone responsible for moving sugar from the blood into the cells to be used for energy.
• Decreasing Sugar Production: Incretins reduce the amount of glucagon released by the pancreas. Glucagon is a hormone that signals the liver to produce more sugar. By lowering glucagon levels, saxagliptin helps prevent the liver from making excess sugar.

By inhibiting the DPP-4 enzyme, saxagliptin allows these incretin hormones to stay active in the body for a longer period. This helps the body better regulate blood sugar levels, particularly after eating. Because the medication primarily works when blood sugar is high, it has a lower risk of causing blood sugar to drop too low (hypoglycemia) when used as a single therapy compared to some other types of diabetes medications.

Common Side Effects

Many people using saxagliptin do not experience significant side effects. When they do occur, common symptoms may include:

• Upper respiratory tract infections, such as the common cold or sore throat
• Urinary tract infections
• Headache
• Stomach pain, nausea, or diarrhea

Serious Side Effects

Contact a healthcare provider immediately if you experience any of the following serious symptoms:

• Pancreatitis: Severe pain in the upper stomach area that may spread to the back, with or without vomiting.
• Heart Failure: Increased shortness of breath, swelling in the feet, ankles, or legs, or unusual tiredness.
• Severe Joint Pain: Pain in the joints that is severe or disabling.
• Skin Reactions: Blisters or the breakdown of the outer layer of skin (bullous pemphigoid).
• Allergic Reactions: Swelling of the face, lips, or throat, difficulty breathing, or a severe skin rash.

Low blood sugar (hypoglycemia) can also occur, particularly if saxagliptin is taken with other diabetes medications like insulin or sulfonylureas. Symptoms of low blood sugar include shakiness, sweating, fast heartbeat, and blurred vision.

Heart Failure Risk

The FDA has issued warnings that saxagliptin may increase the risk of heart failure, particularly in patients who already have heart or kidney disease. Medical attention is necessary if symptoms of heart failure develop, such as:

• Shortness of breath, especially when lying down
• Unusual tiredness or weakness
• Swelling in the ankles, feet, or legs
• Rapid weight gain

Pancreatitis

There have been reports of acute pancreatitis (inflammation of the pancreas) in people taking saxagliptin. This condition can be severe or life-threatening. Symptoms include persistent, severe abdominal pain that may radiate to the back, sometimes accompanied by vomiting. If pancreatitis is suspected, the medication is typically discontinued.

Severe Joint Pain

Some patients taking DPP-4 inhibitors like saxagliptin have experienced severe and disabling joint pain (arthralgia). This can occur within days or years of starting the medication. Symptoms typically resolve after stopping the drug, though some patients may experience a recurrence if they start a different DPP-4 inhibitor.

Allergic Reactions

Serious hypersensitivity reactions have occurred, including anaphylaxis, angioedema (swelling of the face, lips, or throat), and severe skin conditions. Saxagliptin is contraindicated in patients with a history of serious allergic reactions to it or other medications in the same class.

Hypoglycemia

When used in combination with other diabetes medications like insulin or sulfonylureas, the risk of low blood sugar (hypoglycemia) increases. A lower dose of the other medication may be required to reduce this risk. Symptoms of low blood sugar include dizziness, sweating, confusion, and tremors.

Kidney Function

Because saxagliptin is cleared by the kidneys, healthcare providers typically evaluate kidney function before and during treatment. Dosage adjustments are often necessary for patients with moderate to severe kidney impairment or end-stage renal disease.

Bullous Pemphigoid

There have been reports of bullous pemphigoid, a condition that causes large, fluid-filled blisters on the skin. If blistering or skin erosions occur, the medication may need to be discontinued and a referral to a dermatologist may be necessary.

Pregnancy

Data regarding the use of saxagliptin in pregnant women are limited. While animal studies have not shown a high risk of birth defects or developmental issues at standard doses, there are no adequate and well-controlled studies in humans. Because human data are insufficient to inform a drug-associated risk, the medication should be used during pregnancy only if clearly needed.

Maintaining stable blood sugar levels is critical during pregnancy to prevent complications for both the parent and the baby. Healthcare providers often recommend alternative treatments, such as insulin, to manage diabetes during this time because those treatments have more established safety profiles for pregnancy.

Breastfeeding

It is currently unknown whether saxagliptin passes into human breast milk. Because many drugs are excreted in milk and the potential for adverse effects on a nursing infant is not fully understood, caution should be exercised. Patients should discuss the risks and benefits of continuing or stopping the medication while breastfeeding with their healthcare provider to determine the best course of action.

Available Forms

Saxagliptin is currently available in the following form:

• Oral film-coated tablet

This medication is also available in combination with other medications used to treat type 2 diabetes, such as metformin or dapagliflozin, which are also provided in oral tablet forms.

FDA Approval and Indications

Saxagliptin was approved by the U.S. Food and Drug Administration (FDA) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It belongs to a class of medications known as dipeptidyl peptidase-4 (DPP-4) inhibitors. It is not indicated for the treatment of type 1 diabetes or diabetic ketoacidosis.

Safety Communications

In 2016, the FDA issued a safety communication requiring the addition of new warnings to the drug label regarding an increased risk of heart failure. This risk was identified primarily in patients who already had heart or kidney disease. The FDA recommends that healthcare professionals consider discontinuing saxagliptin in patients who develop heart failure and monitor for signs and symptoms of the condition.

Regulatory Warnings and Precautions

The FDA-approved labeling for saxagliptin includes several important safety warnings:

• Heart Failure: Clinical trials observed an increased rate of hospitalization for heart failure in patients treated with saxagliptin.
• Pancreatitis: There have been postmarketing reports of acute pancreatitis. Patients should be monitored for persistent, severe abdominal pain.
• Severe Joint Pain: The FDA has warned that DPP-4 inhibitors may cause severe and disabling joint pain, which may occur at any time during treatment.
• Bullous Pemphigoid: Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use.
• Renal Impairment: Because saxagliptin is partially cleared by the kidneys, the FDA-approved labeling includes specific dosage adjustment recommendations for patients with moderate to severe renal impairment.

FDA Indications

The FDA has approved saxagliptin as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is not indicated for the treatment of type 1 diabetes or diabetic ketoacidosis.

FDA Safety Communications

The FDA has issued specific warnings regarding the use of saxagliptin, including an increased risk of heart failure, particularly in patients who already have heart or kidney disease. Patients should be monitored for signs and symptoms of heart failure, such as shortness of breath, tiredness, or swelling in the ankles and feet.

Additional FDA safety concerns associated with saxagliptin include:

• Pancreatitis: Cases of acute pancreatitis have been reported. The medication should be discontinued if pancreatitis is suspected.
• Severe Joint Pain: The FDA has warned that DPP-4 inhibitors may cause severe and disabling joint pain.
• Bullous Pemphigoid: There have been reports of serious skin reactions that may require medical intervention.
• Hypoglycemia: When used with other diabetes medications like insulin or sulfonylureas, the risk of low blood sugar increases.