Vildagliptin + Metformin

Vildagliptin + Metformin is an anti-diabetic agent belonging to the pharmacological class of Dipeptidyl peptidase-4 (DPP-4) inhibitors and biguanides.

Vildagliptin + Metformin has been approved as a treatment for type 2 diabetes mellitus, helping to control blood sugar levels blood sugar levels by stimulating insulin resistance and enhancing the body's response to insulin.

Vildagliptin is rapidly absorbed, reaching peak plasma concentrations in 1–2 hours. It undergoes extensive metabolism in the liver, primarily via hydrolysis and subsequent excretion through the kidneys. Metformin is absorbed in the gastrointestinal tract, with minimal metabolism, and is eliminated unchanged through the renal system.

Vildagliptin + Metformin side effects that commonly occur include diarrhea, vomiting, nausea, upset stomach, headaches, sore throats, weakness, excessive sweating, and decreased appetite.

Vildagliptin + Metformin is available as a tablet for convenient administration.

Vildagliptin + Metformin is available in India, the United States, Canada, the United Kingdom, Germany, France and Australia.

Vildagliptin + Metformin is an Anti-diabetic Agent belonging to the pharmacological class of Dipeptidyl peptidase-4 (DPP-4) inhibitors. and biguanides.

Vildagliptin: Blood glucose is regulated by vildagliptin by its action on incretin hormones, such as GIP and GLP-1. With GLP-1 influencing insulin production and lowering beta-cell death, these hormones are essential to the insulin response. Blood glucose levels are raised in type 2 diabetes as a result of impaired GLP-1 production and decreased GIP activity. This is remedied by vildagliptin, which inhibits DPP-4, prolonging the half-lives of incretin hormones, and improving their circulation. Better glucose regulation, more insulin production, and higher sensitivity of alpha and beta cells result from this dose-dependent inhibition. Furthermore, by lowering postprandial glucose and fasting, vildagliptin has a beneficial effect on lipid metabolism.

Metformin: Metformin decreases hepatic glucose production, reduces glucose absorption in the intestine and improves insulin sensitivity (increases peripheral glucose uptake and utilization).

Synergistic Benefits: Vildagliptin + Metformin combination has a synergistic effect on type 2 diabetes. Vildagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that increases glucose-dependent insulin production by prolonging the effect of incretin hormones. Metformin lowers glucose production and increases insulin sensitivity. When combined, they offer effective glycemic control by reducing fasting, postprandial, and HbA1c levels.

Vildagliptin + Metformin is available in 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 before meals or generally with a meal.

Vildagliptin + Metformin can be used in the following health conditions:

Vildagliptin: 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.

Metformin: Metformin improves glucose tolerance by lowering basal and postprandial plasma glucose. It exerts its effect by decreasing hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis, delaying intestinal glucose absorption, and increasing insulin sensitivity by increasing peripheral glucose uptake and utilization.

Vildagliptin + Metformin effectively manages Type 2 Diabetes Mellitus by enhancing insulin production, improving insulin utilization, and reducing excess sugar production by the liver. It plays a crucial role in regulating post-meal blood sugar levels, thereby preventing complications such as retinopathy (eyesight loss), nephropathy (kidney issues), neuropathy (nerve damage), diabetic foot ulcers, and delayed wound healing associated with diabetes.

Orally: Vildagliptin + Metformin is available as a tablet that can be taken orally.

It is advised to administered once per day during breakfast or the first main meal and avoid breaking, crushing, dissolving, or chewing pills; swallow them whole with a glass of water. It is best to take it regularly at a fixed time each day following the physician's prescribed schedule for regular and evenly spaced intervals because the dose and duration of therapy are individualized per specific conditions to achieve the most effective and successful treatment outcome.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Vildagliptin + Metformin is available in the form of Oral tablets.

The initial dose for individuals whose metformin hydrochloride monotherapy is not well controlled: Vildagliptin + Metformin may be started at either the 50 mg/500 mg, 50 mg/850 mg, or 50 mg/1,000 mg tablet strength twice daily, depending on the patient's current dose of metformin hydrochloride.

Starting dosage for individuals moving from separate tablet regimens of vildagliptin + metformin hydrochloride combination therapy: Depending on the amount of vildagliptin or metformin already being taken, the 50 mg/500 mg, 50 mg/850 mg, or 50 mg/1,000 mg tablet strength may be used to start vildagliptin + Metformin.

Use in conjunction with insulin or a sulfonylurea: Vildagliptin dosed at 50 mg twice day (100 mg total daily dose) and metformin dosed at a level comparable to the dose currently being taken should be the goals of the Vildagliptin + Metformin dosage.

Vildagliptin + Metformin should be used in treating type 2 diabetes mellitus, along with appropriate dietary restrictions.

Vildagliptin +Metformin is usually taken with meals to lower the risk of gastrointestinal (GI) side effects and to ensure proper absorption.

Limit or avoid alcohol while taking Vildagliptin and Metformin, as alcohol can potentiate the risk of hypoglycemia (low blood sugar).

Limit foods like chips, crisps, pastries, biscuits, and samosas that contain saturated fat, often known as hidden consumption fats. For regular cooking, use oils high in omega-3 fatty acids. One can use safflower oil, rice bran oil, mustard oil, palm oil, and groundnut oil for frying. This involves substituting carbohydrates with whole grains, fruits, and vegetables, as carbohydrates can be converted into sugars, resulting in elevated blood sugar levels. High glycemic foods like potatoes should be avoided due to their potential to raise blood sugar.

The dietary restriction should be individualized as per patient requirements.

Vildagliptin + Metformin may be contraindicated under the following conditions:-

The adverse reactions related to Vildagliptin + Metformin can be categorized as:-

The clinically relevant drug interactions of Vildagliptin + metformin is briefly summarized here:

Vildagliptin + Metformin should be prudent in the following group of special populations.

Pregnancy Category C: Use with caution if the benefits outweigh the risks.

Studies on the teratology (embryofetal development) of metformin hydrochloride and vildagliptin at a 1:10 ratio have been carried out in rats and rabbits. When patients received oral doses up to approximately 14–20 times (for rats) or 1.3-2 times (for rabbits) the maximum authorized clinical dose, there was no sign of teratogenicity. At these levels, there was a rise in early resorptions in rabbits and an increase in the incidence of imperfect ossification in rats. Animal studies may not necessarily anticipate the human reaction, and there are currently insufficient and poorly controlled research conducted on pregnant women.

Vildagliptin + Metformin should therefore not be used when pregnant unless the possible benefit outweighs the possible harm to the developing baby. Because the available data strongly suggests that abnormal blood glucose levels during pregnancy are linked to an increased incidence of congenital anomalies as well as an increased morbidity and mortality of newborns, most experts advise using insulin monotherapy to maintain blood glucose levels as close to normal as possible during pregnancy.

Studies using the combination of metformin + vildagliptin have not been conducted yet. Human breast milk contains metformin excreted in it. Vildagliptin's excretion in human milk is unknown. Breastfeeding women should not take Vildagliptin + Metformin.

As per FDA, safety and effectiveness in the pediatric population have yet to be established.

The total exposure to vildagliptin (100 mg once day) was raised by 32% in otherwise healthy senior adults (≥ 70 years), with an increase in peak plasma concentration of 18% as compared to younger, healthy patients (18 to 40 years). Clinical relevance for these changes is deemed to be low. In the age groups examined, vildagliptin's inhibition of DPP-4 is unaffected by age.

Limited information from controlled pharmacokinetic investigations of metformin hydrochloride in older, healthy adults suggests that, in comparison to young, healthy subjects, metformin hydrochloride has a lower total plasma clearance, a longer half-life, and a higher Cmax. These findings suggest that changes in renal function are the main cause of the aging-related changes in metformin hydrochloride pharmacokinetics.

Patients who are 80 years of age or older should not begin Vildagliptin + Metformin medication unless a measurement of creatinine clearance shows that renal function is not decreased.

Severe (GFR <30 mL/min): Contraindicated.

Hepatic impairment: Contraindicated.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Vildagliptin + Metformin.

Overconsumption of Vildagliptin + Metformin could lead to

severe hypoglycemia (very low blood sugar), gastrointestinal disturbances, such as nausea, vomiting, and diarrhoea, and a risk of lactic acidosis.

There is no specific antidote or treatment for excessive intake of Vildagliptin + Metformin. However, immediate medical attention is essential. Vildagliptin + Metformin should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake. Activated charcoal may be administered to limit further absorption of the drugs.

For hypoglycemia (low blood sugar), consume a source of rapidly absorbed carbohydrates such as glucose tablets, sugar, or honey. Monitor blood glucose levels and repeat treatment if necessary. Intravenous glucose administration may be required to correct the low blood sugar levels rapidly.

Hemodialysis may be considered in severe cases to remove the drugs from the bloodstream. Patients should be closely observed for any signs of lactic acidosis, a rare but potentially life-threatening complication, and treated accordingly.

Vildagliptin: 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.

Metformin: Metformin is an antihyperglycemic medication that lowers basal and postprandial plasma glucose levels in people with type 2 diabetes, improving their glucose tolerance. Its pharmacologic modes of action are distinct from those of other oral antihyperglycemic medication groups. Metformin increases peripheral glucose uptake and utilization, which lowers intestinal glucose absorption, reduces hepatic glucose synthesis, and enhances insulin sensitivity. Metformin, unlike sulfonylureas, does not result in hyperinsulinemia or hypoglycemia in either type 2 diabetes patients or healthy persons. Metformin medication does not alter insulin secretion, although it may reduce the plasma insulin response throughout the day and insulin levels while fasting.

Vildagliptin: 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%.

Metformin: Slowly and incompletely absorbed from the gastrointestinal tract. Food slightly delays and decreases the extent of absorption. Absolute bioavailability: 50-60%. Time to peak plasma concentration: 2-3 hours (immediate-release); 7 hours, range: 4-8 hours (extended-release).

Bioavailability: 50-60% (Metformin [fasted])

Vildagliptin: Following the administration, the mean volume of distribution of vildagliptin at steady-state is 71 L, indicating extravascular distribution.

Metformin: Concentrates in the liver, kidney and gastrointestinal tract. It crosses the placenta and then enters breast milk (small amounts). Volume of distribution: 654 ± 358 L.

Protein-bound: Negligible (Metformin)

Vildagliptin: 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.

Metformin: Excreted unchanged in the urine and did not undergo specific hepatic metabolism (no metabolites have been found in humans) or biliary excretion.

Vildagliptin: 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.

Metformin: With a plasma elimination half-life of roughly 6.2 hours, 90% of the absorbed medication is excreted via the renal pathway during the first 24 hours following oral administration. The elimination half-life of blood is roughly 17.6 hours, indicating that the erythrocyte bulk could constitute a distribution compartment.