Sitagliptin

Primary Uses

Sitagliptin is primarily prescribed to improve blood sugar control in adults with type 2 diabetes mellitus. It helps the body regulate insulin levels after eating, which assists in maintaining healthy blood glucose levels.

How It Is Used

This medication is typically used in the following situations:

• As a standalone treatment when diet and exercise alone are not enough to control blood sugar.
• In combination with other diabetes medications, such as metformin, sulfonylureas, or insulin, when one drug is not sufficient to reach blood sugar goals.

Important Limitations

Sitagliptin is not used for all conditions involving blood sugar. Specifically:

• It is not for the treatment of type 1 diabetes, a condition where the body does not produce insulin.
• It is not used to treat diabetic ketoacidosis, a serious condition involving high levels of acids called ketones in the blood.
• It has not been sufficiently studied for use in children under the age of 18.

How Sitagliptin Works

Sitagliptin belongs to a class of drugs known as dipeptidyl peptidase-4 (DPP-4) inhibitors. It works by increasing the levels of natural substances called incretin hormones in the body.

The Role of Incretin Hormones

Incretin hormones are part of a system that helps the body manage blood sugar, especially after eating. Sitagliptin prevents an enzyme called DPP-4 from breaking down these hormones, allowing them to remain active in the bloodstream for a longer period. This results in two main actions:

• Insulin Release: The hormones signal the pancreas to release more insulin when blood sugar levels are high. Insulin helps move sugar from the blood into the body's cells to be used for energy.
• Sugar Production: The hormones signal the liver to decrease the amount of sugar it produces and releases into the blood.

Because sitagliptin works primarily when blood sugar levels are high, it helps lower blood glucose without typically causing blood sugar to drop too low when used alone. It is used to manage type 2 diabetes and is not effective for treating type 1 diabetes.

Common Side Effects

• Stuffy or runny nose and sore throat
• Headache
• Nausea, diarrhea, or stomach pain
• Upper respiratory tract infection

Serious Side Effects

Seek medical attention immediately if you experience any of the following serious symptoms:

• Pancreatitis: Severe pain in the upper stomach that may spread to the back, with or without vomiting.
• Allergic Reactions: Swelling of the face, lips, tongue, or throat; hives; or difficulty breathing.
• Severe Skin Reactions: Blistering or peeling of the skin (bullous pemphigoid).
• Severe Joint Pain: Persistent or disabling pain in the joints.
• Kidney Problems: Swelling in the legs or feet, or changes in the frequency or amount of urination.
• Heart Failure: Shortness of breath (especially when lying down), unusual tiredness, or sudden weight gain.

Low blood sugar (hypoglycemia) is more likely to occur if sitagliptin is taken with other diabetes medications, such as insulin or sulfonylureas. Symptoms of low blood sugar include shakiness, sweating, rapid heartbeat, and dizziness.

Pancreatitis

Inflammation of the pancreas (pancreatitis) is a serious side effect reported in people taking sitagliptin. This condition can be severe or life-threatening. It is important to stop taking the medication and seek medical attention immediately if severe stomach pain occurs that may spread to the back, with or without vomiting.

Heart Failure

Some people taking DPP-4 inhibitors like sitagliptin have developed heart failure. Signs to watch for include increasing shortness of breath, unusual tiredness, or swelling in the feet, ankles, or legs.

Kidney Function

Sitagliptin is primarily cleared by the kidneys. Healthcare providers typically check kidney function before starting the medication and periodically during treatment. Dosage adjustments may be necessary for individuals with moderate to severe kidney disease or end-stage renal failure.

Low Blood Sugar (Hypoglycemia)

When sitagliptin is used with other diabetes medications, such as insulin or sulfonylureas, the risk of low blood sugar increases. A lower dose of the other medication may be required to reduce this risk. Symptoms of low blood sugar include shakiness, sweating, fast heartbeat, and blurred vision.

Severe Allergic Reactions

Serious hypersensitivity reactions have occurred, including anaphylaxis, swelling of the face, lips, or throat (angioedema), and severe skin conditions like Stevens-Johnson syndrome. These reactions usually happen within the first three months of treatment but can occur after the first dose.

Joint Pain and Skin Reactions

Severe and disabling joint pain has been reported in patients taking this class of drugs. Additionally, a skin condition called bullous pemphigoid, which causes large, fluid-filled blisters, may occur. If these symptoms develop, the medication may need to be discontinued.

Pregnancy

There is limited information regarding the safety of sitagliptin during pregnancy. While animal studies have not demonstrated a risk of birth defects or other harm to the fetus, there are no adequate and well-controlled studies in humans to confirm its safety. Maintaining stable blood sugar control is critical during pregnancy to reduce the risk of complications for both the parent and the baby.

If you are pregnant or planning to become pregnant, talk to your healthcare provider. They will evaluate whether the benefits of using sitagliptin outweigh the potential risks or if another treatment, such as insulin, is more suitable for managing blood glucose levels during this time.

Breastfeeding

It is currently unknown if sitagliptin passes into human breast milk. Research in animals has shown that the drug can be present in milk, but these findings do not always predict what happens in humans. Because many drugs are excreted in human milk, caution is advised.

Consult with a healthcare professional to weigh the benefits of breastfeeding against the potential risks to the infant while taking this medication. They can help determine the best course of action for your specific situation.

Available Forms

Sitagliptin is available as a film-coated tablet for oral administration.

Combination Products

This medication is also available in combination with other active ingredients, such as metformin. These combination products are provided in the following forms:

• Oral tablets
• Extended-release oral tablets

FDA Approval and Indications

Sitagliptin was approved by the U.S. Food and Drug Administration (FDA) in 2006. It is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is not approved for use in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

Safety Communications

The FDA has monitored and issued communications regarding several safety concerns for sitagliptin:

• Pancreatitis: Postmarketing reports have identified cases of acute pancreatitis, including serious hemorrhagic or necrotizing forms. The FDA advises healthcare providers to monitor patients for persistent severe abdominal pain and to discontinue the drug if pancreatitis is suspected.
• Nitrosamine Impurities: In 2022, the FDA alerted the public to the presence of a nitrosamine impurity, Nitroso-STG-19 (NTTP), in certain batches of sitagliptin. To prevent a medication shortage, the FDA permitted the temporary distribution of sitagliptin with NTTP levels above the standard intake limit while manufacturers worked to improve quality control.
• Severe Joint Pain: The FDA has warned that the class of drugs known as DPP-4 inhibitors, which includes sitagliptin, may cause severe and disabling joint pain.
• Heart Failure: Class-wide reviews of DPP-4 inhibitors have suggested a potential increased risk of heart failure, particularly in patients who already have heart or kidney disease.

Regulatory Status

Sitagliptin is available only by prescription. It does not currently require a Risk Evaluation and Mitigation Strategy (REMS). While sitagliptin as a single-ingredient product does not carry a boxed warning, combination products that include sitagliptin and metformin do contain a boxed warning regarding the risk of lactic acidosis.

Weight Neutrality

Sitagliptin is classified as a weight-neutral medication. Unlike some other treatments for type 2 diabetes, such as insulin or sulfonylureas, sitagliptin is not associated with weight gain in most clinical studies. It is also not considered a weight-loss drug, as it does not typically cause significant weight reduction on its own.

Factors Influencing Weight

While sitagliptin itself does not usually change a person's weight, weight changes may occur due to other factors while taking the medication:

• Combination Therapy: Sitagliptin is often prescribed alongside other medications like metformin. Metformin is sometimes associated with modest weight loss, which may be observed when the two drugs are used together.
• Lifestyle Changes: Patients are typically advised to follow a specific diet and exercise plan while taking sitagliptin. Any weight loss achieved is often the result of these lifestyle modifications rather than the drug itself.
• Comparison to Other Drugs: Sitagliptin does not affect appetite or digestion in the same way as GLP-1 receptor agonists, which are a different class of diabetes medications known to promote weight loss.