Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral prescription medications used to manage blood sugar levels. These medications work by targeting a specific enzyme in the body, helping individuals with type 2 diabetes achieve better glycemic control.
How DPP-4 Inhibitors Work
DPP-4 inhibitors function by interacting with the dipeptidyl peptidase-4 enzyme, which naturally exists in the body. This enzyme is responsible for breaking down incretin hormones, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Incretin hormones are released by the gut in response to food intake and play a significant role in glucose regulation.
By blocking the DPP-4 enzyme, these inhibitors allow GLP-1 and GIP to remain active in the bloodstream for a longer duration. This extended activity leads to several beneficial effects on blood sugar control. For instance, when blood sugar levels are high, increased incretin levels stimulate the pancreas to release more insulin.
Additionally, these elevated incretin levels help reduce the liver’s production of glucose. They also suppress the secretion of glucagon, another hormone that raises blood sugar levels. The combined effect of increased insulin release and decreased glucose production helps lower both fasting and post-meal blood glucose concentrations in individuals with type 2 diabetes.
Role in Type 2 Diabetes Treatment
DPP-4 inhibitors are prescribed to improve glycemic control in adults with type 2 diabetes, often as an adjunct to diet and exercise. A healthcare provider might consider these medications as an initial therapy, particularly if metformin is not suitable, or as an add-on to other antidiabetic agents already being taken. They are effective when used alone or in combination with medications like metformin, sulfonylureas, or thiazolidinediones.
These inhibitors help reduce glycated hemoglobin (HbA1c) levels, which is a measure of average blood sugar over two to three months. Clinical studies have shown that DPP-4 inhibitors can lead to clinically significant HbA1c reductions. Common examples of DPP-4 inhibitors include sitagliptin, marketed as Januvia; saxagliptin, known by the brand name Onglyza; and linagliptin, sold as Tradjenta. Alogliptin (Nesina) and vildagliptin (Galvus, though not approved in the U.S.) are also part of this class. These medications are typically taken as oral tablets once daily.
Potential Side Effects
While generally well-tolerated, DPP-4 inhibitors can cause some side effects. More common and less severe effects may include upper respiratory tract infections, headaches, and gastrointestinal discomfort such as nausea or diarrhea. Some individuals might also experience flu-like symptoms, including a runny nose or sore throat. These effects often diminish as the body adjusts to the medication.
Less common but more serious risks associated with DPP-4 inhibitors warrant attention. Pancreatitis, an inflammation of the pancreas, has been reported in association with these drugs. Patients should be aware of symptoms like persistent, severe abdominal pain that may radiate to the back, sometimes accompanied by nausea or vomiting. The U.S. Food and Drug Administration (FDA) has also warned that DPP-4 inhibitors may cause severe and disabling joint pain (arthralgia). Rarely, severe allergic reactions, such as rash, hives, or swelling of the face or throat, can also occur.
Important Patient Considerations
Patients considering or taking DPP-4 inhibitors should discuss their complete medical history with their doctor. Individuals with a history of pancreatitis should inform their healthcare provider, as DPP-4 inhibitors are generally not recommended in such cases due to a potential increased risk. Although some studies suggest no increased risk of pancreatitis, caution is still advised.
Kidney function is another important factor, as dosage adjustments may be necessary for most DPP-4 inhibitors if a patient has impaired renal function. For example, sitagliptin doses may be reduced for moderate or severe kidney impairment, while linagliptin typically does not require dose adjustment regardless of kidney function. Patients with heart failure, especially those with more advanced stages, also require careful consideration, as some DPP-4 inhibitors, like saxagliptin and alogliptin, have been linked to an increased risk of hospitalization for heart failure.
Regarding interactions with other medications, DPP-4 inhibitors usually have few significant drug-drug interactions. However, when combined with sulfonylureas or insulin, there is an increased risk of low blood sugar (hypoglycemia). In such cases, a dose reduction of the sulfonylurea or insulin may be advised to mitigate this risk. Saxagliptin, specifically, is metabolized by certain liver enzymes (CYP3A4/5), so its levels can be affected by strong inhibitors or inducers of these enzymes, such as ketoconazole or rifampicin.