Vildagliptin

Vildagliptin is an oral antidiabetic drug that is used to treat type 2 diabetes mellitus. It belongs to the class of dipeptidyl peptidase-4 (DPP-4) inhibitors.

Vildagliptin is used to improve blood glucose control in adults with type 2 diabetes mellitus . It is usually prescribed in combination with other antidiabetic medications such as metformin, sulfonylureas or insulin.

Vildagliptin is available as a mono or combination preparation in tablet form for oral administration. As a combination preparation, it is only available with metformin.

Vildagliptin exerts its blood glucose-lowering effect by selectively inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4), which rapidly cleaves and inactivates glucagon-like peptide-1 (GLP-1) and glucose-independent peptide (GIP) after their release from intestinal cells. Inhibition of DPP-4 significantly prolongs the half-life of GLP-1 and GIP, thereby increasing the levels of active circulating incretin hormones. Incretins are hormones produced by the intestine in response to food intake and stimulate the release of insulin from the pancreas. The increased release of insulin causes glucose to be absorbed from the blood into the cells, thus lowering blood sugar levels. In addition to its effect on insulin secretion, GLP-1 is also involved in promoting the new formation (neogenesis) and differentiation of islet cells and in attenuating cell death (apoptosis) of pancreatic beta cells. Incretin hormones also have effects outside the pancreas, for example on fat formation (lipogenesis) and heart muscle function.

The duration of DPP-4 inhibition by vildagliptin is dose-dependent. Vildagliptin lowers fasting and prandial blood glucose and HbA1c levels. It increases the glucose sensitivity of alpha and beta cells and increases glucose-dependent insulin secretion.

The bioavailability of vildagliptin, i.e. the percentage of the active substance available in the blood, is 85%. In the fasting state, vildagliptin is rapidly absorbed after oral administration. The half-life, i.e. the time the body needs to excrete half of the active substance, is 2-3 hours. The maximum plasma concentration (Cmax), i.e. the maximum concentration of the active substance in the blood plasma (liquid cell-free part of the blood), is reached 1 - 2 hours after administration. Food delays the time to 2.5 hours and reduces the maximum plasma concentration by 19 %, but has no effect on the overall exposure to the drug. The plasma protein binding of vildagliptin is 9.3 %. The majority of orally administered vildagliptin is metabolized via a non-cytochrome P450 enzyme-mediated metabolism. After oral administration, approximately 85% of the vildagliptin dose is excreted in the urine and approximately 15% of the dose was eliminated in the feces.

Always take vildagliptin exactly as described in the package leaflet or as advised by your doctor.

The usual recommended dose is 50 mg twice a day, which may be adjusted according to the patient's individual response to treatment.

The following side effects may occur:

• Symptoms indicating an allergic reaction: swollen face, tongue or throat, difficulty swallowing, difficulty breathing, sudden skin rash or hives
• Symptoms that indicate liver disease: Symptoms such as yellowing of the skin and eyes, nausea, loss of appetite or dark-colored urine
• Symptoms of inflammation of the pancreas: severe and persistent abdominal pain that can radiate to the back and nausea and vomiting

Other side effects that may occur:

• sore throat
• runny nose
• fever
• Itchy skin rash
• trembling
• headache
• dizziness
• Muscle pain
• joint pain
• constipation
• swollen hands, ankles or feet (edema)
• excessive sweating
• vomiting
• Pain in the stomach and around the stomach (abdominal pain)
• diarrhea
• heartburn
• Nausea
• blurred vision
• weight gain
• chills
• feeling weak
• sexual disorders
• low blood sugar
• flatulence
• inflammation of the pancreas

Interactions may occur if the following medicines are taken at the same time:

• Thiazides or other diuretics
• Corticosteroids for the treatment of inflammation
• Thyroid medication
• Medications that affect the nervous system

Vildagliptin must NOT be taken in the following cases

• in case of allergy to vildagliptin

Vildagliptin should NOT be taken by anyone under the age of 18.

Vildagliptin should NOT be taken during pregnancy & breastfeeding as there is limited data on the safety of vildagliptin.

Vildagliptin was first approved for use in Europe in 2007 and subsequently in other countries, including Japan, Canada and Mexico. It is not yet approved in the United States.