Remogliflozin Etabonate + Vildagliptin

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

Remogliflozin Etabonate + Vildagliptin has been approved for treating type 2 diabetes Mellitus by facilitating urinary sugar elimination and enhancing insulin release from the pancreas.

The drugs Remogliflozin Etabonate + Vildagliptin are used orally. Remogliflozin is rapidly and widely absorbed in the digestive system and then converted to active metabolites. Vildagliptin is similarly absorbed and then processed by the liver very rapidly. Both are eliminated mainly by the kidneys, which excrete them in urine as metabolites.

Remogliflozin Etabonate + Vildagliptin side effects commonly include diarrhea, nausea, vomiting, upset stomach, and headache.

Remogliflozin Etabonate + Vildagliptin is available as a tablet for convenient administration.

Remogliflozin Etabonate + Vildagliptin is available in the United States, European countries (such as Germany, France, and the United Kingdom), Japan, India, and Australia.

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

Remogliflozin Etabonate: Remogliflozin etabonate inhibits glucose reabsorption in the kidneys by inhibiting SGLT2. As a result, blood glucose levels are lowered due to increased glucose excretion in urine. It lowers blood sugar levels independently of insulin action by blocking the body from reabsorbing glucose and encouraging the excretion of excess glucose. Using the kidneys to eliminate excess glucose helps control hyperglycemia and provides a different approach from other antidiabetic drugs, concentrating on insulin synthesis or sensitivity. In people with type 2 diabetes, the inhibition of SGLT2 helps with urine excretion of glucose, which improves glycemic control.

Vildagliptin: Vildagliptin increases fasting and postprandial endogenous levels of the incretin hormones GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide) as it wholly and rapidly inhibits DPP-4 action.

Synergistic Benefits: Vildagliptin + remogliflozin etabonate works synergistically to manage type 2 diabetes. Vildagliptin increases insulin release and reduces blood glucose-raising hormones, whereas remogliflozin etabonate decreases blood glucose levels by encouraging urine sugar excretion. Because of this synergism, glucose regulation is better controlled because it effectively targets several pathways. They provide better overall metabolic control and enhanced diabetes management, possibly lowering the risk of related consequences, including cardiovascular illnesses.

Remogliflozin Etabonate + Vildagliptin 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 twice daily before meals or generally with a meal.

Remogliflozin Etabonate + Vildagliptin can be used in the following health conditions:

Remogliflozin Etabonate: Controlling elevated blood sugar levels is the main objective of type 2 diabetes mellitus therapy. Urine is used to get rid of extra glucose in this way. It is necessary to lower blood glucose; controlling and lowering high blood sugar levels is essential to diabetes treatment.

Vildagliptin: Vildagliptin helps treat Type 2 diabetes mellitus by increasing 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 twice per day.

Vildagliptin + remogliflozin etabonate efficiently treats type 2 diabetes. Vildagliptin decreases hormones that raise blood sugar and increases insulin production from the pancreas, while remogliflozin etabonate helps the body get rid of extra sugar through the urine. To effectively treat type 2 diabetes, this combination works together to control blood sugar levels.

When an adult with type 2 diabetes mellitus is 18 years of age or older, it is indicated:

To enhance glycemic control in cases when Vildagliptin and Metformin alone cannot offer sufficient glycemic control or in cases where Vildagliptin and Remogliflozin Etabonate have been administered with the essential combination.

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

It is advised to administer two times daily before meals 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.

Remogliflozin Etabonate + Vildagliptin is available in the form of Oral tablets.

Metformin alone or combined with thiazolidinedione, insulin, or both: Dosage recommendation: 50 mg twice daily or 100 mg daily.

Using a Sulphonylurea in a Dual Combination:

50 mg once daily in the morning is the recommended dosage.

When 100 mg was taken daily instead of 50 mg once a day, no extra efficacy was seen.

Consider a Lower Sulphonylurea Dose When Using It: Reduce the dosage of sulphonylurea to lessen the chance of hypoglycemia.

Monotherapy and Add-on Therapy with Metformin:

Recommended dose: Remogliflozin Etabonate 100 mg twice daily.

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

Exercise caution with alcohol consumption as it can increase the risk of hypoglycemia, especially when combining Vildagliptin with other glucose-lowering medications.

Patients should limit high-carbohydrate, high-sugar foods to maintain stable glucose levels.

This involves substituting carbohydrates with whole grains, fruits, vegetables, and lean proteins, as carbohydrates can be converted into sugars, resulting in elevated blood sugar levels.

The dietary restriction should be individualized as per patient requirements.

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

Gastrointestinal disorders: Pancreatitis

Hepatobiliary diseases: Hepatitis, abnormal liver function tests.

Musculoskeletal and connective tissue disorders: Myalgia

Skin and subcutaneous tissue disorders: Urticaria, exfoliative and bullous skin lesions, including bullous pemphigoid.

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

The most common side effects of Remogliflozin Etabonate + Vildagliptin include:

Stomach upset

Diarrhoea

Headache

Nausea

Ketonuria

Constipation

Dyslipidemia

Vomiting

Tremors

Urinary tract infection

Respiratory tract infection

Hypoglycemia (low blood glucose level)

Remogliflozin Etabonate + Vildagliptin should be prudent in the following population group.

The presence of remogliflozin etabonate or remogliflozin (active moiety) in human breast milk is unknown, and no clinical trials with pregnant or nursing women have been carried out with this medication. It is not advisable to take remogliflozin etabonate whilst pregnant or nursing. Women who are or may become pregnant should not become pregnant before remogliflozin etabonate is administered, and they should use recommended contraceptives. ORAL hormonal contraceptives may not be an effective method of contraception due to the probable absorption-affecting impact of remogliflozin etabonate; instead, a suitable alternate means of preventing pregnancy should be employed.

Remogliflozin etabonate did not affect the fertility of male rats (200, 600, and 1200 mg/kg/day; oral) or female rats (200, 600, and 1000 mg/kg/day; oral). The NOAEL was 1200 mg/kg/day (approximately 58 times the maximum recommended human daily dose (MRHDD) of 100 mg twice daily (200 mg/day) on a body surface area [mg/m2] basis. The NOAEL was 1000 mg/kg/day (approximately 49 times the MRHDD of 200 mg/day on a mg/m2 basis), respectively. Oral dosages of 1000 and 500 mg/kg/day (or around 49 times the MRHDD of 200 mg/day on a mg/m2 basis) of remogliflozin etabonate did not cause teratogenic effects in rats (200, 600, and 1000 mg/kg/day) or rabbits (125, 250, and 500 mg/kg/day). No treatment-related effects were observed in pregnant or lactating females or on the development of the conceptus and the offspring following exposure up to 1000 mg/kg/day (approximately 49 times the MRHDD of 200 mg/day on mg/m2 basis) in a pre-and post-natal developmental study conducted in rats (200, 600, and 1000 mg/kg/day; oral).

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.

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.

No studies on the effect on human fertility have been conducted for vildagliptin.

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

The safety and effectiveness of Remogliflozin Etabonate + Vildagliptin in geriatric patients have yet to be extensively studied. Caution is advised due to potential age-related renal function decline, requiring close monitoring for adverse effects and dosage adjustments.

Elderly (≥ 65 years): No dose adjustments are necessary in elderly patients.

eGFR ≥ 50 ml/min (mild renal impairment): No dose adjustment is needed for Vildagliptin.

Moderate or severe renal impairment or end-stage renal disease (ESRD): Use Vildagliptin cautiously.

Remogliflozin is not recommended for moderate to severe renal impairment (CrCl < 60 ml/min or eGFR < 60 ml/min/1.73 m2).

No dose adjustment for mild renal impairment.

Remogliflozin Specific Guidelines:

Avoid initiating Remogliflozin if GFR < 60 mL/min.

Discontinue Remogliflozin at GFR < 45 mL/min.

Hepatic Impairment: Not recommended.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Remogliflozin Etabonate + Vildagliptin. Overconsumption of Remogliflozin Etabonate + Vildagliptin could lead to severe hypoglycemia, dehydration, gastrointestinal disturbances, or electrolyte imbalances.

There is no specific antidote or treatment for excessive Remogliflozin Etabonate + Vildagliptin intake. However, immediate medical attention is essential. Remogliflozine etabonate + Vildagliptin should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake. Treatment might involve symptomatic and supportive measures.

When managing severe hypoglycemia, administer oral glucose or intravenous dextrose if necessary.

If the patient is conscious and the intake was recent, consider administrating activated charcoal. In severe cases or persistent metabolic abnormalities, hospitalisation is necessary for extensive observation and supportive care.

Remogliflozin Etabonate: Remogliflozin etabonate is quickly absorbed and transforms into remogliflozin in its active state. Food consumption slightly postpones the peak concentration without changing the overall exposure, giving administrators more choices. Mean Cmax and AUC0-tau values are observed at steady state levels at 100 mg and 250 mg dosages in Indian individuals with type 2 diabetes. In one investigation, absorption of over 93% was noted. Given their nearly complete absorption, remogliflozin etabonate and remogliflozin function as P-gp substrates rather than inhibitors, suggesting that P-gp inhibitors have no apparent effect on their pharmacokinetics.

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.

Remogliflozin Etabonate: Remogliflozin etabonate is swiftly absorbed and converted to active forms like remogliflozin. Remogliflozin etabonate is absorbed quickly and converted to active forms like remogliflozin. Absorption exceeds 93%, acting as a P-gp substrate, not an inhibitor. Therefore, P-gp inhibitors aren't expected to affect its pharmacokinetics.

Vildagliptin: When 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%.

Remogliflozin Etabonate: Approximately 65% of remogliflozin is bound to plasma proteins. The distribution of remogliflozin etabonate or remogliflozin was not preferential to blood cells, nor did remogliflozin or its metabolites selectively associate with tissues that contained melanin.

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

Remogliflozin Etabonate: Numerous metabolic processes occur throughout the extended metabolism of remogliflozin etabonate, including oxidation, glucose loss, glucuronidation, N-dealkylation, O-dealkylation, and loss of ethyl hydrogen carbonate.

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.

Remogliflozin Etabonate: The prodrug's average plasma half-life within the identical investigation ranged from 0.4 to 0.7 hours. A little over 11% of the dose was recovered as remogliflozin in the urine of the radiolabeled AME trial, which expelled about 93% of the drug; most drug-related material is removed in the urine as inactive glucuronide metabolites.

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.