Vildagliptin
Vildagliptin Uses, Dosage, Side Effects, Food Interaction and all others data.
Vildagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, Vildagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner.
Vildagliptin works to improve glycemic control in type II diabetes mellitus by enhancing the glucose sensitivity of beta-cells (β-cells) in pancreatic islets and promoting glucose-dependent insulin secretion. Increased GLP-1 levels leads to enhanced sensitivity of alpha cells to glucose, promoting glucagon secretion. Vildagliptin causes an increase in the insulin to glucagon ratio by increasing incretin hormone levels: this results in a decrease in fasting and postprandial hepatic glucose production. Vildagliptin does not affect gastric emptying. It also has no effects on insulin secretion or blood glucose levels in individuals with normal glycemic control.
In clinical trials, treatment with vildagliptin 50-100 mg daily in patients with type 2 diabetes significantly improved markers of beta-cells, proinsulin to insulin ratio, and measures of beta-cell responsiveness from the frequently-sampled meal tolerance test. Vildagliptin has improves glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels.
| Trade Name | Vildagliptin |
| Generic | Vildagliptin |
| Vildagliptin Other Names | Vildagliptin, Vildagliptina |
| Type | |
| Formula | C17H25N3O2 |
| Weight | Average: 303.3993 Monoisotopic: 303.194677059 |
| Protein binding | The plasma protein binding of vildagliptin is 9.3%. Vildagliptin distributes equally between plasma and red blood cells. |
| Groups | Approved, Investigational |
| Therapeutic Class | Dipeptidyl Peptidase-4 (DPP-4) inhibitor |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Vildagliptin is used for an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
- As monotherapy
- In dual combination with Metformin, a Sulphonylurea, a Thiazolidinedione, or Insulin when diet, exercise and a single antidiabetic agent do not result in adequate glycemic control.
Vildagliptin is also used to associated treatment for these conditions: Type 2 Diabetes Mellitus
How Vildagliptin works
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are incretin hormones that regulate blood glucose levels and maintain glucose homeostasis. It is estimated that the activity of GLP-1 and GIP contribute more than 70% to the insulin response to an oral glucose challenge. They stimulate insulin secretion in a glucose-dependent manner via G-protein-coupled GIP and GLP-1 receptor signalling. In addition to their effects on insulin secretion, GLP-1 is also involved in promoting islet neogenesis and differentiation, as well as attenuating pancreatic beta-cell apoptosis. Incretin hormones also exert extra-pancreatic effects, such as lipogenesis and myocardial function. In type II diabetes mellitus, GLP-1 secretion is impaired, and the insulinotropic effect of GIP is significantly diminished.
Vildagliptin exerts its blood glucose-lowering effects by selectively inhibiting dipeptidyl peptidase-4 (DPP-4), an enzyme that rapidly truncates and inactivates GLP-1 and GIP upon their release from the intestinal cells. DPP-4 cleaves oligopeptides after the second amino acid from the N-terminal end. Inhibition of DPP-4 substantially prolongs the half-life of GLP-1 and GIP, increasing the levels of active circulating incretin hormones. The duration of DPP-4 inhibition by vildagliptin is dose-dependent. Vildagliptin reduces fasting and prandial glucose and HbA1c. It enhances the glucose sensitivity of alpha- and beta-cells and augments glucose-dependent insulin secretion. Fasting and postprandial glucose levels are decreased, and postprandial lipid and lipoprotein metabolism are also improved.
Dosage
Vildagliptin dosage
The recommended dose of Vildagliptin is-
- 50 mg or 100 mg daily for monotherapy.
- 50 mg twice daily (morning and evening) when used in dual combination with Metformin or a Thiazolidinedione;
- 50 mg once daily in the morning when used in dual combination with a Sulphonylurea.
Vildagliptin may be taken with or without a meal. No dosage adjustment is required in the elderly, or in patients with mild renal impairment.
Side Effects
The majority of adverse reactions were mild and transient, not requiring treatment discontinuations. Rare case of hepatic dysfunction is seen. Clinical trials of up to and more than 2 years’ duration did not show any additional safety signals or unforeseen risks when use this drug.
Toxicity
The oral Lowest published toxic dose (TDLO) is 0.3 mg/kg in rats and 1 mg/kg in mice.
There is limited information regarding overdose with vildagliptin. In one study, patients experienced muscle pain, mild and transient paresthesia, fever, edema, and a transient increase in lipase levels at a dose of 400 mg. At 600 mg, one subject experienced edema of the feet and hands and increases in creatine phosphokinase (CPK), aspartate aminotransferase (AST), C-reactive protein (CRP) and myoglobin levels. Supportive management is recommended in case of an overdose. There is no known antidote, and vildagliptin and its major metabolite cannot be removed via hemodialysis.
Precaution
Caution should be exercised in patients aged 75 years and older due to limited clinical experience. It is recommended that Liver Function Tests (LFTs) are monitored prior to initiation of Vildagliptin, at three monthly intervals in the first year and periodically thereafter. If transaminase levels are increased, patients should be monitored with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality (ies) return(s) to normal. If AST or ALT persist at 3 x ULN, Vildagliptin treatment should be stopped. Patients who develop jaundice or other signs of liver dysfunction should discontinue Vildagliptin. Following withdrawal of treatment with Vildagliptin and LFT normalization, treatment with Vildagliptin should not be reinitiated. Due to limited clinical experience, use with caution in patients with congestive heart failure of New York Heart Association (NYHA) functional class I–II, and do not use in patients with NYHA functional class III-IV. Vildagliptin is not recommended in patients with moderate to severe renal impairment.
Interaction
In pharmacokinetic studies, no interactions were seen with pioglitazone, metformin, glibenclamide, digoxin, warfarin, amlodipine, ramipril, valsartan or simvastatin. As with other oral antidiabetic medicinal products the glucose-lowering effect of Vildagliptin may be reduced by certain active substances, including thiazides, corticosteroids, thyroid products and sympathomimetics.
Food Interaction
- Take with or without food. Food reduces Cmax and delays Tmax, but not in a clinically significant way.
Volume of Distribution
The mean volume of distribution of vildagliptin at steady-state after intravenous administration is 71 L, suggesting extravascular distribution.
Elimination Route
In a fasting state, vildagliptin is rapidly absorbed following oral administration. Peak plasma concentrations are observed at 1.7 hours following administration. Plasma concentrations of vildagliptin increase in an approximately dose-proportional manner.
Food delays Tmax to 2.5 hours and decreases Cmax by 19%, but has no effects on the overall exposure to the drug (AUC). Absolute bioavailability of vildagliptin is 85%.
Half Life
The mean elimination half-life following intravenous administration is approximately two hours. The elimination half-life after oral administration is approximately three hours.
Clearance
After intravenous administration to healthy subjects, the total plasma and renal clearance of vildagliptin were 41 and 13 L/h, respectively.
Elimination Route
Vildagliptin is eliminated via metabolism. Following oral administration, approximately 85% of the radiolabelled vildagliptin dose was excreted in urine and about 15% of the dose was recovered in feces. Of the recovered dose in urine, about 23% accounted for the unchanged parent compound.
Pregnancy & Breastfeeding use
Pregnancy: There are no adequate data on the use of Vildagliptin in pregnant women; hence the potential risk for human is unknown.Lactation: It is not known whether Vildagliptin is excreted in human milk. Due to lack of human data, Vildagliptin should not be used during lactation.
Contraindication
Vildagliptin is contraindicated in patients with:
- Hypersensitivity to the active substance or to any of the excipients
- Patients with type 1 diabetes or for the treatment of diabetic ketoacidosis
Special Warning
Paediatric use: Vildagliptin is not recommended in patients 18 years of age
Storage Condition
Store in a cool and dry place. Protect from light and moisture. Keep out of the reach of the children.
Innovators Monograph
You find simplified version here Vildagliptin
Vildagliptin contains Vildagliptin see full prescribing information from innovator Vildagliptin Monograph, Vildagliptin MSDS, Vildagliptin FDA label
FAQ
What are the uses of Vildagliptin?
Vildagliptin is used for the treatment of Type 2 diabetes mellitus. This is used along with diet and exercise to improve blood sugar control in adults with Type 2 diabetes.
What are the common side effects of Vildagliptin?
Some of the common and major side effects of Vildagliptin are:
- Headache
- Cough
- Constipation
- Sweating
- Hypoglycaemia
- Weakness
- Excessive sweating
- Heartburn
- Swelling of face, lips and eyelids
When should I take Vildagliptin?
You can take the Vildagliptin tablets before, during or after meals.If you have been told to take two doses each day, take your first dose in the morning and the second dose in the evening.
How does Vildagliptin work in the body?
It works by blocking the breakdown of incretin hormones in the body. These hormones are released after a meal and stimulate the pancreas to produce insulin.
Is Vildagliptin safe during pregnancy?
You should not take this Vildagliptin during pregnancy. There are no adequate data from the use of Vildagliptin in pregnant women. Due to lack of human data, you should not be used during pregnancy.
Is Vildagliptin safe during breastfeeding?
You should not use Vildagliptin if you are breast-feeding or plan to breast-feed. A safety Score of indicates that usage of Vildagliptin may cause some minor side effects in breastfed baby.Study of different scientific research indicates that Vildagliptin may cause moderate to no side effects in lactating mother.
Can I drink alcohol with Vildagliptin?
Taking Vildagliptin with alcohol may affect the control of your blood glucose.
Can I drive after taking Vildagliptin?
If you feel dizzy while taking this medicine, do not drive or use machines.
How do you take Vildagliptin?
You can take Vildagliptin any time of day ,just try to take it at the same time every day.The usual dose is 1 tablet taken once a day.Vildagliptin can be taken with or without food. Swallow the tablets whole with a glass of water.
How safe is Vildagliptin?
Vildagliptin is a safe therapeutic option for patients with T2DM, both as monotherapy and as add-on treatment.Vildagliptin is approved for use as monotherapy and in combination with other anti-hyperglycaemic agents.
Is Vildagliptin good for diabetes?
Vildagliptin is an important and well-tolerated treatment choice for elderly patients with type 2 diabetes, showing comparable glycemic regulation to metformin but having better GI tolerability.
Is Vildagliptin safe for long term?
Vildagliptin as add-on to insulin treatment for 24 months was well tolerated and led to sustained reductions in HbA1c, the dose and frequency of insulin injections, and the risk of hypoglycemia in patients with T2DM.
Does Vildagliptin cause weight loss?
Vildagliptin may cause modest weight loss has been observed in patients with relatively low baseline glycemia.
Is Vildagliptin safe for kidneys?
Vildagliptin can be safely used in T2DM patients with varying degrees of renal impairment.Dose adjustments for renal impairment are required.
What class of drug is Vildagliptin?
Vildagliptin is a member of a class of oral antidiabetic agents known as dipeptidyl peptidase IV inhibitors (DPP-IV) inhibitors or 'incretin enhancers'.
Can I stop taking Vildagliptin?
Do not stop taking Vildagliptin suddenly; speak to your doctor or nurse before stopping.
Does Vildagliptin cause hypoglycemia?
Vildagliptin treatment has consistently been associated with a low incidence of hypoglycemia in all clinical settings, including more vulnerable populations at higher risk for hypoglycemia, such as elderly patients or patients treated with insulin.
