Usage
- Remogliflozin Etabonate + Vildagliptin is prescribed for the treatment of Type 2 diabetes mellitus in adults over 18 years of age, as an adjunct to diet and exercise. It is specifically indicated for patients whose blood sugar levels are inadequately controlled with Metformin alone or in combination with other antidiabetic agents. It is not indicated for Type 1 diabetes or diabetic ketoacidosis.
- Pharmacological Classification: Antidiabetic combination drug; specifically a combination of a sodium-glucose co-transporter-2 (SGLT2) inhibitor (Remogliflozin Etabonate) and a dipeptidyl peptidase-4 (DPP-4) inhibitor (Vildagliptin).
- Mechanism of Action: This combination works through two distinct mechanisms:
- Remogliflozin Etabonate: Inhibits SGLT2 in the kidneys, blocking glucose reabsorption and increasing its excretion in urine, thereby lowering blood glucose levels.
- Vildagliptin: Inhibits DPP-4, an enzyme that breaks down incretin hormones. This leads to increased levels of incretins, which stimulate insulin release and decrease glucagon secretion, further contributing to blood glucose control.
Alternate Names
While there are no official alternate names for the combination itself, the individual components have chemical names:
- Remogliflozin etabonate: (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol 1,3,4,5-tetraacetate.
- Vildagliptin: (2S)-1-[(3-hydroxy-1-adamantyl)amino]acetyl-2-pyrrolidinecarbonitrile.
Some brand names under which this fixed-dose combination is marketed include Remo V, Remozen-V, and others (the availability of specific brands may vary regionally).
How It Works
- Pharmacodynamics: The combined effect of remogliflozin and vildagliptin results in a significant reduction in HbA1c, fasting plasma glucose (FPG), and postprandial plasma glucose (PPG) levels. Remogliflozin also has a modest blood pressure-lowering effect and can contribute to weight loss.
- Pharmacokinetics:
- Absorption: Both drugs are orally absorbed.
- Metabolism: Remogliflozin is primarily metabolized in the liver by CYP enzymes (mainly CYP2C8 and CYP3A4). Vildagliptin is primarily metabolized by hydrolysis to its inactive metabolite. A small portion is also metabolized by CYP2C8 and CYP3A4.
- Elimination: Remogliflozin is eliminated through both renal and hepatic routes, with urine being the primary route. Vildagliptin is primarily eliminated renally, with a small portion eliminated in feces.
- Mode of Action:
- Remogliflozin: Acts by directly binding to and inhibiting SGLT2 in the renal proximal tubules, preventing glucose reabsorption from the glomerular filtrate back into the bloodstream.
- Vildagliptin: Acts by binding to and inhibiting DPP-4, thereby increasing the concentration of incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones enhance glucose-dependent insulin secretion, suppress glucagon secretion, and slow gastric emptying.
Dosage
Standard Dosage
Adults:
- The recommended starting dose is Remogliflozin 100 mg + Vildagliptin 50 mg twice daily, taken orally with meals.
- The dose may be adjusted based on the patient’s glycemic control and tolerability. The maximum recommended dose of remogliflozin is 200 mg twice daily, while the maximum dose of vildagliptin is 100 mg daily (either as 50 mg twice daily or 100 mg once daily).
Children:
- This combination is not recommended for use in children below 18 years of age, as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Dosage should be initiated cautiously, starting with the lowest dose and gradually titrated upwards based on the patient’s renal function and glycemic control.
- Patients with Renal Impairment: The dose should be adjusted based on the estimated glomerular filtration rate (eGFR). Remogliflozin is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73m²). Vildagliptin dose reduction is recommended for moderate to severe renal impairment.
- Patients with Hepatic Dysfunction: Caution should be exercised in patients with hepatic impairment. Remogliflozin dose reduction is recommended for moderate to severe hepatic impairment. Vildagliptin can generally be used without dose adjustment in mild to moderate hepatic impairment.
- Patients with Comorbid Conditions: Care should be taken when using this combination in patients with cardiovascular disease, especially those at risk of hypotension or those using diuretics. Close monitoring of blood pressure is recommended.
Clinical Use Cases
The combination of remogliflozin and vildagliptin is not specifically indicated for use in settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. Its primary use is in the chronic management of type 2 diabetes.
Dosage Adjustments
Dose adjustments should be made based on patient-specific factors like renal or hepatic dysfunction, other comorbid conditions, and concomitant medications.
Side Effects
Common Side Effects
- Upper respiratory tract infections
- Nasopharyngitis
- Headache
- Urinary tract infections (UTIs)
- Genital fungal infections
- Nausea
- Diarrhea
- Hypoglycemia (especially when combined with sulfonylureas or insulin)
Rare but Serious Side Effects
- Diabetic ketoacidosis (DKA)
- Acute pancreatitis
- Severe hypoglycemia
- Angioedema
- Hypotension (low blood pressure)
- Volume depletion/dehydration
Long-Term Effects
- Increased risk of bone fractures (with SGLT2 inhibitors)
- Potential for renal impairment (requiring regular monitoring)
Adverse Drug Reactions (ADR)
Any instance of angioedema, severe hypoglycemia, DKA, or acute pancreatitis should be considered serious and warrants immediate discontinuation of the drug and appropriate medical intervention.
Contraindications
- Hypersensitivity to remogliflozin, vildagliptin, or any component of the formulation
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- Severe renal impairment (eGFR < 30 mL/min/1.73m²)
- End-stage renal disease requiring dialysis
- Severe hepatic impairment
Drug Interactions
- Diuretics: Increased risk of dehydration and hypotension.
- Insulin and Sulfonylureas: Increased risk of hypoglycemia.
- Corticosteroids: May reduce the blood glucose-lowering effect of remogliflozin and vildagliptin.
- Digoxin: Remogliflozin can increase digoxin levels.
- CYP3A4 substrates (e.g., simvastatin): Remogliflozin can increase concentrations of some CYP3A4 substrates.
Pregnancy and Breastfeeding
- Pregnancy: The safety of remogliflozin and vildagliptin during pregnancy has not been established. Their use is generally not recommended unless the benefits clearly outweigh the risks.
- Breastfeeding: It is unknown whether remogliflozin and vildagliptin are excreted in human milk. Their use during breastfeeding is generally not recommended.
Drug Profile Summary
- Mechanism of Action: Remogliflozin: SGLT2 inhibition; Vildagliptin: DPP-4 inhibition.
- Side Effects: UTIs, genital infections, headache, nausea, hypoglycemia, dehydration.
- Contraindications: Hypersensitivity, type 1 diabetes, DKA, severe renal impairment, pregnancy, breastfeeding.
- Drug Interactions: Diuretics, corticosteroids, insulin, sulfonylureas, digoxin, CYP3A4 substrates.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: 100 mg/50 mg twice daily, adjusted based on patient factors.
- Monitoring Parameters: HbA1c, FPG, PPG, renal function (eGFR, creatinine), blood pressure, liver function tests, volume status.
Popular Combinations
- Remogliflozin + Vildagliptin + Metformin: This triple combination is used in patients whose blood sugar levels are not adequately controlled with dual therapy.
Precautions
- General Precautions: Assess renal function, hepatic function, and cardiovascular risk factors before initiating therapy. Monitor for hypoglycemia, especially when combined with insulin or sulfonylureas.
- Specific Populations: Pregnancy and Breastfeeding: Avoid use unless absolutely necessary. Children: Not recommended. Elderly: Start with a lower dose and monitor closely.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Remogliflozin Etabonate + Vildagliptin?
A: The standard starting dose for adults is 100 mg remogliflozin + 50 mg vildagliptin twice daily. Dosage adjustments may be necessary for elderly patients, patients with renal or hepatic impairment, and those with other medical conditions.
Q2: How should this medication be taken?
A: Orally, twice daily with meals.
Q3: What are the most common side effects?
A: Headache, nasopharyngitis, UTIs, genital infections, nausea, and hypoglycemia.
Q4: Can this medicine be taken during pregnancy or breastfeeding?
A: It is not recommended during pregnancy or breastfeeding due to potential risks. Consult a doctor for alternative treatment options.
Q5: What should I do if I miss a dose?
A: If you miss a dose, take it as soon as you remember, unless it is close to your next scheduled dose. Do not double the dose.
Q6: Does this medication interact with other drugs?
A: Yes, it can interact with several medications, including diuretics, insulin, sulfonylureas, corticosteroids, and certain drugs metabolized by CYP3A4. Inform your doctor about all medications you are taking, including over-the-counter drugs and supplements.
Q7: Can this medicine be taken with alcohol?
A: Alcohol consumption should be limited while taking this medication as it can increase the risk of hypoglycemia and other side effects.
Q8: Can this medication cure diabetes?
A: No, it does not cure diabetes. It helps manage blood sugar levels and reduce the risk of long-term complications associated with diabetes.
Q9: How long will I need to take this medication?
A: The duration of treatment depends on your individual condition and response to the medication. Your doctor will determine the appropriate duration of treatment.
Q10: Does this combination have any effect on weight?
A: Remogliflozin, a component of the combination, can cause a modest amount of weight loss due to increased urinary glucose excretion.
