Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
Vildagliptin has been given approval to treat hyperglycemia in people with type 2 diabetes by increasing the release of insulin from the pancreas and decreasing the production of glucose in the liver, it helps to regulate and lower high blood sugar levels.
Vildagliptin is an Antidiabetic Agent belonging to the pharmacological class of Dipeptyl peptidase-4 (DPP-4) inhibitors.
Incretin hormones that control blood glucose levels and preserve glucose homeostasis include glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). An oral glucose challenge is thought to trigger an insulin response in which GLP-1 and GIP activity account for about 70% of the reaction. G-protein-coupled GIP and GLP-1 receptor signalling induce insulin secretion in a glucose-dependent way. GLP-1 influences insulin production, promotes islet neogenesis and differentiation and reduces pancreatic beta-cell death. Incretin hormones also affect processes outside the pancreas, like lipogenesis and heart function.3- GLP-1 secretion is disrupted in type II diabetes mellitus, and GIP's insulinotropic action is markedly reduced.
By explicitly blocking dipeptidyl peptidase-4 (DPP-4), an enzyme that quickly truncates and inactivates GLP-1 and GIP following their release from intestinal cells, vildagliptin lowers blood glucose levels. Following the second amino acid from the N-terminal end, DPP-4 cleaves oligopeptides. The half-lives of GLP-1 and GIP are significantly extended by inhibition of DPP-4, which raises the amount of incretin hormones that are actively circulating. Vildagliptin's inhibition of DPP-4 has a dose-dependent duration. Vildagliptin lowers HbA1c, prandial glucose, and fasting glucose. It increases glucose-dependent insulin secretion and the sensitivity of alpha and beta cells to glucose. Postprandial lipid and lipoprotein metabolism is enhanced, and fasting and postprandial glucose levels are reduced.
Vildagliptin is available in the form of Oral Tablets.
Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.
As the physician recommends, take the medication orally once daily, generally with or without a meal.
- Vildagliptin is used primarily to help regulate and lower increased blood sugar levels in treating type 2 diabetes mellitus.
- It can be used as part of a broad diabetes management approach or in combination with other antidiabetic drugs.
- It enhances insulin release from the pancreas and reduces the liver's glucose production, helping to regulate blood sugar.
- It is used to enhance insulin release from the pancreas and reduces the liver's glucose production, helping regulate blood sugar.
In Treatment of Type 2 diabetes mellitus
Vildagliptin helps increase the amount of insulin produced after a meal and stops the body from releasing too much glucose (sugar) into the blood. This way, it reduces the blood glucose levels in the body. It often only causes a single frequent adverse effect and is taken once each day.
To effectively manage diabetes, the blood glucose levels must be reduced. Controlling blood sugar levels will lower the likelihood of any of the severe complications of diabetes, including kidney damage, eye damage, nerve problems, and amputation of limbs. The risk of cardiac disease and stroke can be decreased with proper diabetes management. Individuals can live longer if they take this medication consistently and follow a healthy diet and exercise routine.
For patients with type 2 diabetes mellitus, vildagliptin is indicated as an adjunct to diet and exercise to improve glycemic management.
- As monotherapy.
- When diet, exercise, and one antidiabetic medication are insufficient to produce adequate glycemic control when combined with metformin, sulphonyl urea (SU), or thiazolidinedione (TZD).
- When diet, exercise, and dual therapy with these drugs are insufficient to provide appropriate glycemic control, in triple combination with sulphonyl urea and metformin.
- When diet, exercise, and continuous insulin dosage cannot produce sufficient glycemic control, in addition to insulin (with or without metformin).
Orally: Vildagliptin is available in oral tablet form and can be taken on an empty stomach or with food. For optimal results, adhere to a regular daily schedule as your healthcare provider prescribes. Dosage and treatment duration are customized to individual conditions. The 50 mg dose is taken once daily in the morning, while the 100 mg dose consists of two divided 50 mg doses in the morning and evening. If a dose is missed, take it as soon as remembered; do not double the amount on the same day.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Vildagliptin is available in the form of Oral Tablets.
Dose Adjustment in Adult Patients:
Vildagliptin is recommended to be used as monotherapy, in combination with metformin, thiazolidinedione, metformin, and sulphonylurea, or combination with insulin (with or without metformin). As a daily dose, vildagliptin should be taken as 50 mg PO in the morningand 50 mg PO in the evening.
Vildagliptin is recommended at a dose of 50 mg once daily, to be taken in the morning when combined with sulphonylurea. Vildagliptin 50 mg once a day was just as beneficial in this patient group as vildagliptin 100 mg daily.
A reduced dose of sulphonylurea may be considered when administered in conjunction with another medication to lessen the possibility of hypoglycemia.
It is not advised to use doses greater than 100 mg. The patient should administer Vildagliptin as soon as they remember if a dosage is missed but on the same day, the extra dose shouldn't be taken.
Vildagliptin, metformin, and thiazolidinedione used as a triple oral treatment have not been safe or effective.
Vildagliptin should be used in treating Type 2 Diabetes Mellitus, along with appropriate nutritional limits.
While taking Vildagliptin, maintain regular meals with balanced macronutrient content to help stabilize blood sugar levels and prevent overeating.
Limit or avoid the intake of alcohol as it can interfere with blood sugar regulation.
Avoid consuming sugary foods and beverages, including cereals, snacks, and sweetened beverages, as they can lead to rapid spikes in blood glucose.
It is advised to stay hydrated, maintain a rich, balanced diet with appropriate carbohydrate intake, and consume plenty of vegetables, whole grains, fruits, and lean proteins to help manage your overall health and blood sugar levels effectively.
The dietary restriction should be individualized as per patient requirements.
- For people who need insulin, vildagliptin is not a substitute for insulin. Those who have type 1 diabetes or who are treating diabetic ketoacidosis shouldn't use vildagliptin.
- Post-marketing reports of exfoliative and bullous skin lesions have been reported.Thus, monitoring for skin conditions like blistering or ulceration is advised as part of the diabetic patient's regular care.
- The chance of experiencing acute pancreatitis has been linked to vildagliptin usage.It is essential to ensure that patients know acute pancreatitis's hallmark symptom. Vildagliptin should not be started again if acute pancreatitis is proven; instead, it should be stopped if pancreatitis is suspected. Patients who have previously experienced acute pancreatitis should use caution.
- To establish a baseline, liver function tests must be performed before initiating vildagliptin therapy. After the first year, it is important to monitor liver function periodically, then every three months. A second assessment is recommended for patients whose transaminase levels are higher. Stopping vildagliptin is advised if elevated AST or ALT values remain three times ULN or above. If liver dysfunction symptoms such as jaundice develop, stop taking vildagliptin. When liver function tests have returned to normal, it is not advised to resume vildagliptin.
- There is a known risk of hypoglycemia from sulphonylureas. Individuals taking sulphonylurea along with vildagliptin may be susceptible to hypoglycemia. Consequently, a lesser dose of sulphonylurea may be used to lessen the chance of hypoglycemia.
- Lactose is found in the pills. Individuals who suffer from glucose-galactose malabsorption, Lapp lactase deficiency, or rare genetic galactose intolerance should not use this medication.
Alcohol Warning
Breast Feeding Warning
There is no sufficient scientific evidence traceable regarding the use and safety of Vildagliptin in breastfeeding.
Pregnancy Warning
Food Warning
- Common Adverse Effects: Urinary tract infection, headache, headaches, and nasopharyngitis.
- Less Common Adverse Effects: Hypoglycemia, Gastroenteritis, allergic reactions, Peripheral oedema, and pancreatitis.
- Rare Adverse Effects: Hypersensitivity, severe joint pain, bullous pemphigoid
- The clinically relevant drug interactions of Vildagliptin are briefly summarized here:
- CYP3A4 Inducers and Inhibitors: Medications that induce or inhibit the CYP3A4 enzyme can affect the metabolism of Vildagliptin. Inducers like rifampin may reduce Vildagliptin's effectiveness, while inhibitors like ketoconazole can increase its concentration in the body.
- Sulfonylureas and Insulin: Combining Vildagliptin with other antidiabetic medications like sulfonylureas or insulin may increase the risk of hypoglycemia (low blood sugar). Dose adjustments may be necessary.
- ACE Inhibitors and ARBs: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are used to manage high blood pressure. Combining them with Vildagliptin may lead to a more significant reduction in blood pressure.
- Cyclosporine: The immunosuppressant drug cyclosporine may increase Vildagliptin levels in the body. Close monitoring is advised when these medications are used together.
- Beta-Adrenergic Blockers: Beta-blockers may mask the symptoms of hypoglycemia, making it harder to detect low blood sugar levels in individuals taking Vildagliptin.
The most common side effects of Vildagliptin include:
- Hypoglycemia, or low blood glucose
- Tremors
- A headache
- Lightheadedness
- Tiredness
- Feeling sick
- Nausea
- Pregnancy
Pregnancy Category B; Could be acceptable. Either no danger has been shown by animal research, but human studies have yet to be conducted, or some risk has been shown by animal studies but not by human studies.
Vildagliptin use in pregnant women has not provided sufficient data. Reproductive damage at high doses has been demonstrated in animal studies. The potential risk to people is not known. It is not recommended to use vildagliptin when pregnant.
- Nursing Mothers
Vildagliptin may or may not be eliminated from human milk. Studies on animals have demonstrated that vildagliptin is excreted in milk. Vildagliptin should not be taken while nursing a baby.
- Pediatric Use
As per FDA, Vildagliptin is not recommended for use in children and adolescents (< 18 years). Safety and effectiveness in the pediatric population under 18 years of age have not been established.
- Geriatric Use
It is essential to closely monitor the safety and usage of vildagliptin in older people. Individualized dosage and monitoring possible drug interactions and side effects are crucial. Blood sugar levels should be monitored often since older persons may be more susceptible to hypoglycemia. For proper management, consulting with a healthcare professional is essential.
Dosage adjustment in geriatric patients
Dose adjustments is not necessary for elderly patients (over 65 years).
Dose Adjustment in Kidney Impairment Patients:
Patients with mild renal impairment (the creatinine clearance ≥ 50 ml/min) do not require dose adjustment.
The recommended dosage of vildagliptin in individuals with end-stage renal disease (ESRD) or moderate to severe renal impairment is 50 mg once a day.
Dose Adjustment in Hepatic Impairment Patients:
Patients with hepatic impairment, such as those with pre-treatment ALT or AST levels greater than three times the upper limit of normal (ULN), should not use vildagliptin.
Signs and Symptoms
The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of vildagliptin.
Overconsumption of vildagliptin could lead to symptoms such as mild and transient paresthesia, fever, oedema and a transient increase in lipase levels, swelling of hands and feet, and increases in creatine phosphokinase (CPK), aspartate aminotransferase (AST), C-reactive protein (CRP) and myoglobin levels.
Management
There is no specific antidote or treatment for excessive intake of vildagliptin. However, immediate medical attention is essential. Vildagliptin should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake. Activated charcoal can help bind to the medication and limit its absorption, mainly if the overdose is recent.
Mild episodes of hypoglycemia can be primarily treated with oral glucose, whereas severe hypoglycemia with seizure, coma, or neurological impairment can be treated with glucagon or intravenous (IV) glucose. In Severe hypoglycemic reactions, hospitalization may be necessary to monitor and treat the individual until their blood sugar levels are stable.
Supportive care like addressing symptoms and complications, continuous vital signs and blood glucose monitoring, and maintaining hydration and electrolyte balance should be given to difficulties.
Pharmacodynamics:
Vildagliptin increases the glucose sensitivity of beta-cells (β-cells) in the pancreatic islets and stimulates glucose-dependent insulin production, which helps to improve glycemic control in type II diabetes mellitus. Elevated GLP-1 levels stimulate glucagon release by improving alpha cells' sensitivity to glucose. By raising incretin hormone levels, vildagliptin increases the insulin-to-glucagon ratio, which lowers postprandial hepatic glucose production and fasting. Gastritin does not alter the process of stomach emptying. Additionally, it does not affect blood glucose levels or insulin secretion in people with standard glycemic control.
The proinsulin-to-insulin ratio, beta-cell responsiveness metrics from the frequently-sampled meal tolerance test, and beta-cell marker levels considerably improved in type 2 diabetes patients receiving vildagliptin 50–100 mg daily during clinical trials. Vildagliptin levels of fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) are improved.
Pharmacokinetics:
Absorption
When vildagliptin is taken orally during fasting, it is absorbed quickly. At 1.7 hours after treatment, peak plasma concentrations are seen. The rise in vildagliptin plasma concentrations is approximately dose-proportional. Food has little influence on the total exposure to the medication (AUC), although it does reduce Cmax by 19% and delay Tmax by 2.5 hours. Vildagliptin has an absolute bioavailability of 85%.
Distribution
Following the administration, the mean volume of distribution of vildagliptin at steady-state is 71 L, indicating extravascular distribution.
Metabolism
About 69% of orally administered vildagliptin is eliminated via metabolism not mediated by cytochrome P450 enzymes. Based on the findings of a rat study, DPP-4 contributes partially to the hydrolysis of vildagliptin. Vildagliptin is metabolized to pharmacologically inactive cyano (57%) and amide (4%) hydrolysis products in the kidney. LAY 151 (M20.7) is a major inactive metabolite and a carboxylic acid formed via hydrolysis of the cyano moiety; it accounts for 57% of the dose. Other circulating metabolites reported are an N-glucuronide (M20.2), an N-amide hydrolysis product (M15.3), and two oxidation products, M21.6 and M20.9.
The plasma protein binding of vildagliptin is 9.3%. Vildagliptin is distributed equally between plasma and red blood cells.
Elimination
Metabolic processes excrete Vildagliptin. Approximately 85% of the radiolabelled vildagliptin dosage was eliminated through urine after oral delivery, with the remaining 15% being recovered in faeces. About 23% of the urine's recovered dose comprised the unaltered parent component.
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- Matthews, David R et al. "Glycaemic Durability of an Early Combination Therapy with the Vildagliptin and Metformin Vs Sequential Metformin Monotherapy in Newly Diagnosed Type 2 Diabetes (VERIFY): a 5-Year, Multicentre, Randomised, Double-Blind Trial." The Lancet (British edition) 394.10208 (2019): 1519–1529. Web.
- McMurray JJV, et al; VIVIDD Trial Committees and Investigators. Effects of Vildagliptin on Ventricular Function in the Patients With Type 2 Diabetes Mellitus and Heart Failure: A Randomized Placebo-Controlled Trial. JACC Heart Fail. 2018 Jan;6(1):8-17. doi: 10.1016/j.jchf.2017.08.004. Epub 2017 Oct 11. PMID: 29032139.
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