Dipeptidyl peptidase-4 (DPP-4) inhibitors represent a class of oral prescription medications developed to help manage Type 2 diabetes. These medications work by engaging with the body’s own internal systems to regulate blood sugar levels, supporting its natural processes for glucose control. They are typically prescribed as part of a comprehensive diabetes management plan.
How DPP-4 Inhibitors Lower Blood Sugar
The body naturally produces hormones called incretins, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These incretin hormones are released into the bloodstream after a meal, playing a role in stimulating the pancreas to release insulin and reducing the amount of glucagon produced by the liver. Insulin works to move sugar from the blood into cells for energy, while glucagon raises blood sugar levels.
A naturally occurring enzyme, dipeptidyl peptidase-4 (DPP-4), rapidly breaks down these beneficial incretin hormones, limiting their duration of action. Think of the DPP-4 enzyme as a switch that quickly turns off the helpful effects of GLP-1 and GIP. DPP-4 inhibitors work by blocking this specific enzyme, preventing it from inactivating the incretins.
By inhibiting the DPP-4 enzyme, these medications allow GLP-1 and GIP to remain active in the body for a longer period. This sustained activity leads to an enhanced, glucose-dependent release of insulin and a reduction in glucagon secretion. The overall result is improved control over blood sugar levels, particularly after meals.
Types of DPP-4 Medications
Several DPP-4 inhibitor medications are available. Each medication contains a unique active ingredient, but all function by blocking the DPP-4 enzyme.
One widely used DPP-4 inhibitor is sitagliptin (Januvia). Another option is saxagliptin, marketed as Onglyza. Linagliptin, sold under the brand name Tradjenta, is also part of this class of drugs. Alogliptin, known as Nesina, completes the primary group of DPP-4 inhibitors available. These medications are typically taken once daily.
Associated Side Effects and Health Warnings
Like all medications, DPP-4 inhibitors can cause side effects, ranging from common and mild to rare but serious. Common, less severe side effects may include headache, a stuffy or runny nose, or a sore throat. Some individuals might also experience upper respiratory tract infections.
More serious potential side effects include inflammation of the pancreas, known as pancreatitis, which is a rare but severe concern. Symptoms of pancreatitis can include intense and persistent abdominal pain that might radiate to the back, sometimes accompanied by vomiting. Individuals experiencing such symptoms should seek immediate medical attention.
Severe and disabling joint pain, or arthralgia, has also been reported with the use of DPP-4 inhibitors. This pain can develop anywhere from a single day to several years after starting the medication. Often, the joint pain subsides after discontinuing the drug.
Additionally, an increased risk of heart failure is associated with certain DPP-4 inhibitors, namely saxagliptin and alogliptin. Symptoms of heart failure include increasing shortness of breath, swelling in the feet, ankles, or legs, unusual and rapid weight gain, or unusual tiredness. Patients should discuss any concerns about these serious side effects with their healthcare provider.
Use in Combination with Other Diabetes Therapies
DPP-4 inhibitors play a role in the broader management of Type 2 diabetes, either used alone or as part of a multi-drug regimen. While they can be prescribed as a single therapy, they are frequently added to existing diabetes treatments. A common combination involves their use alongside metformin, a medication that reduces glucose production by the liver and improves the body’s sensitivity to insulin.
Combining DPP-4 inhibitors with metformin is beneficial because these medications work through different mechanisms. Metformin addresses insulin resistance and hepatic glucose output, while DPP-4 inhibitors enhance the body’s natural incretin response, stimulating insulin secretion when blood sugar is high.
DPP-4 inhibitors may also be combined with other classes of diabetes medications, such as sulfonylureas or sodium-glucose cotransporter-2 (SGLT2) inhibitors. While DPP-4 inhibitors generally have a low risk of causing low blood sugar (hypoglycemia) when used alone, this risk may increase when combined with certain other medications like sulfonylureas or insulin.