Vildagliptin + Dapagliflozin

Vildagliptin + Dapagliflozin is an Anti-diabetic Agent belonging to the pharmacological class of Dipeptidyl peptidase-4 (DPP-4) inhibitors and Sodium-glucose transport protein 2 (SGLT2) Inhibitors.

Vildagliptin + Dapagliflozin has been approved as a treatment for type 2 diabetes mellitus by promoting insulin release and reducing glucose reabsorption in the kidneys, ultimately improving overall glycemic control.

Vildagliptin + Dapagliflozin is absorbed after oral administration, undergoes metabolism primarily in the liver, and is eliminated through renal and fecal routes.

Vildagliptin + Dapagliflozin side effects that commonly occur include vulvovaginitis, balanitis and related genital infections, urinary tract infections, hypoglycemia, dizziness, tremors, and headache.

Vildagliptin + Dapagliflozin is available as a film-coated tablet for convenient administration.

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

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 circulation. This dose-dependent inhibition results in better glucose regulation, more insulin production, and higher sensitivity of alpha and beta cells. Furthermore, by lowering postprandial glucose and fasting, vildagliptin has a beneficial effect on lipid metabolism.

Dapagliflozin: The sodium-glucose co-transporter 2 (SGLT2), primarily found in the proximal tubule of the nephron, is inhibited by Dapagliflozin. Because SGLT2 supports 90% of the kidneys' glucose reabsorption, its blockage permits glucose excretion in the urine. Patients with type 2 diabetes mellitus may greatly benefit from improved glycemic control and possible weight loss due to this excretion.

Synergistic Benefits: Vildagliptin + Dapagliflozin work together to help control blood sugar levels, reduce the excess sugar produced by the liver, improve insulin sensitivity and mitigate the risk of complications associated with diabetes such as retinopathy, nephropathy, neuropathy, diabetic foot ulcers, and delayed wound healing.

Data Onset of action of Vildagliptin + Dapagliflozin typically occurs within a few hours after administration.

Data duration of action of Vildagliptin + Dapagliflozin effects generally lasts throughout the day.

The Data of Tmax and Cmax of Vildagliptin + Dapagliflozin has yet to be established.

Vildagliptin + Dapagliflozin 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 with a meal.

Vildagliptin + Dapagliflozin 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.

Dapagliflozin: For people with type 2 diabetes, the drug Dapagliflozin provides several benefits. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors like Dapagliflozin promote the excretion of extra glucose through the urine, improving blood sugar regulation and perhaps resulting in weight loss.

Dual action benefits: Vildagliptin promotes urine glucose excretion by inhibiting renal glucose reabsorption and lowering glucagon levels, while dapagliflozin increases insulin secretion. Combining them helps reduce blood sugar, enhance glycemic management, and promote weight loss. Additionally, by improving insulin sensitivity and lowering the risk of cardiovascular events, this combination helps regulate blood sugar levels.

Vildagliptin + Dapagliflozin is used to treat type 2 diabetes when:

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

It is advised to administer once daily 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 + Dapagliflozin is available in the form of Oral tablets.

Dose: Vildagliptin + Dapagliflozin initial recommended dose is 5mg +100 mg PO OD with or without meals at any time of the day.

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

Vildagliptin + Dapagliflozin 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 + Dapagliflozin, 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. For frying, one can use safflower oil, rice bran oil, mustard oil, palm oil, and groundnut oil. 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 + Dapagliflozin may be contraindicated under the following conditions:-

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

The clinically relevant drug interactions of Vildagliptin + Dapagliflozin are briefly summarized here:

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

Pregnancy Category C(FDA): Use caution if the benefits outweigh the risks.

If a woman is pregnant, breastfeeding suspects pregnancy, or plans to conceive, seeking advice from a healthcare professional is crucial before using Vildagliptin + Dapagliflozin. The medication is not recommended during pregnancy; if pregnancy occurs, the doctor will advise discontinuation.

The impact of Vildagliptin + Dapagliflozin on human breast milk is unknown; therefore, breastfeeding while using this medicine is not recommended. Women should discuss alternative methods to control blood sugar during pregnancy and explore suitable options with their healthcare provider. The decision to use the medication during breastfeeding should be made in consultation with a doctor, considering potential risks and benefits.

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

Renal impairment: Contraindicated.

Hepatic impairment: Contraindicated.

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

Overconsumption of Vildagliptin + Dapagliflozin could lead to severe hypoglycemia (low blood sugar), dizziness, tremors, headache, fatigue, nausea, rash, and potential complications like dyslipidemia and dehydration.

There is no specific antidote or treatment for excessive intake of Vildagliptin + Dapagliflozin. However, immediate medical attention is essential. Vildagliptin + Dapagliflozin should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake.

In cases of severe hypoglycemia, administration of glucose or glucagon may be necessary. Adequate fluid intake is crucial to address potential dehydration. Monitoring blood glucose levels, electrolytes, and renal function is essential.

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.

Dapagliflozin: Dapagliflozin increases the amount of sodium delivered to the distal tubule while decreasing its reabsorption. After receiving Dapagliflozin, both healthy individuals and patients with type 2 diabetes mellitus showed increases in the amount of glucose expelled in their urine, and in the patients with type 2 diabetes mellitus, dapagliflozin dosages of 5 or 10 mg per day for 12 weeks led to an excretion of about 70 grams of glucose per day in the urine by Week 12. At a daily dose of 20 mg of Dapagliflozin, a near-maximum glucose excretion was noted. Dapagliflozin-induced increases in urine volume are also a consequence of this glucose excretion in the urine. The rise in urine glucose excretion for the 10 mg dose often returns to baseline three days after stopping Dapagliflozin. Dapagliflozin was not associated with a clinically significant lengthening of the QTc interval in a trial of healthy subjects at daily doses up to 150 mg (15 times the maximum amount advised). Moreover, in healthy individuals, a single amount of Dapagliflozin up to 500 mg (50 times the recommended maximum dose) did not cause a change in the QTc interval that was clinically significant.

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%.

Dapagliflozin: When Dapagliflozin is taken orally, maximal concentration is attained during fasting for around two hours. AUC and Cmax grow in direct proportion to dosage. At 10 mg, the bioavailability is 78%. The AUC is unaffected when taken with a high-fat meal, but Cmax and Tmax are slightly lowered. People can take Dapagliflozin with or without food.

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

Dapagliflozin: Roughly 91% of Dapagliflozin is linked to proteins. Patients with renal or hepatic impairment do not have altered protein binding.

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.

Dapagliflozin: UGT1A9 is the main enzyme involved in dapagliflozin metabolism, with CYP-mediated metabolism as a minor human clearance mechanism. Dapagliflozin undergoes much metabolism, primarily producing the inactive metabolite dapagliflozin 3-O-glucuronide. Dapagliflozin 3-O-glucuronide is the main drug-related component in human plasma, accounting for 61% of a 50 mg [14C]-dapagliflozin dosage.

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 Dapagliflozin: Renal elimination is the primary method to eliminate dapagliflozin and its associated metabolites. After a single 50 mg dose of [14C]-Dapagliflozin, the amount of radioactivity excreted in the urine is 75%, whereas the amount in the faeces is 21%. Less than 2% of the dosage is eliminated as a parent drug in the urine. About 15% of the dosage is destroyed as a parent drug in stools. After taking 10 mg of Dapagliflozin, Dapagliflozin's mean plasma terminal half-life (t¬) is about 12.9 hours.