Usage
- This triple-drug combination is prescribed for adults with type 2 diabetes mellitus to improve glycemic control when metformin plus either remogliflozin or vildagliptin alone does not provide adequate blood sugar control. It is also an option when a patient is already taking metformin and one of the other two drugs as separate tablets.
- Pharmacological Classification: Antidiabetic agent, a combination of a biguanide (metformin), 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 three different mechanisms to lower blood sugar:
- Metformin: Decreases hepatic glucose production, reduces intestinal glucose absorption, and improves insulin sensitivity.
- Remogliflozin Etabonate: Inhibits SGLT2 in the kidneys, increasing urinary glucose excretion.
- Vildagliptin: Inhibits DPP-4, increasing incretin levels (like GLP-1 and GIP), which stimulate insulin release and suppress glucagon secretion.
Alternate Names
- No widely recognized alternate names exist for this specific combination. However, it is sometimes referred to as a triple fixed-dose combination (FDC) of metformin, remogliflozin, and vildagliptin.
- Brand Names: One example is REMO MV500 (India). Brand names can vary regionally.
How It Works
- Pharmacodynamics: The combined effects of the three drugs result in improved glycemic control through reduced glucose production, increased glucose excretion, and enhanced insulin secretion while suppressing glucagon.
- Pharmacokinetics:
- Metformin: Absorbed in the gastrointestinal tract, not metabolized, and excreted renally.
- Remogliflozin Etabonate: Orally absorbed, metabolized primarily via glucuronidation, and excreted in urine and feces.
- Vildagliptin: Orally absorbed, metabolized primarily by hydrolysis and to a lesser extent by CYP3A4, and excreted in urine and feces.
- Mode of Action:
- Metformin’s exact mechanism is not fully understood but involves activation of AMP-activated protein kinase (AMPK).
- Remogliflozin selectively inhibits SGLT2 in the renal proximal tubules.
- Vildagliptin selectively and reversibly inhibits DPP-4.
- Elimination Pathways: Predominantly renal excretion for metformin; both renal and hepatic (via glucuronidation) for remogliflozin; primarily renal and to a lesser extent hepatic (hydrolysis and CYP3A4 metabolism) for vildagliptin.
Dosage
Standard Dosage
Adults:
- Typical starting dose: Remogliflozin 100mg + Vildagliptin 50mg + Metformin 500mg or 1000 mg twice daily, taken before meals. Dosages are adjusted based on individual patient needs and responses.
- Maximum dose: The maximum daily dose for each component should be considered.
Children:
- Not recommended for use in children below 18 years of age due to lack of safety and efficacy data.
Special Cases:
- Elderly Patients: Careful dose titration is essential. Start with the lowest dose and increase gradually while closely monitoring renal function.
- Patients with Renal Impairment: Contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73m²). Dose adjustments may be needed for mild to moderate renal dysfunction.
- Patients with Hepatic Dysfunction: Use with caution in patients with hepatic dysfunction. Monitor liver function tests.
- Patients with Comorbid Conditions: Consider adjusting the dose based on coexisting conditions like cardiovascular disease or other metabolic disorders.
Clinical Use Cases
- The specific use cases mentioned (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations) are not typical clinical settings for initiating or adjusting this medication. Diabetes management is usually handled peri-operatively by adjusting insulin regimens.
Dosage Adjustments
- Dosage adjustments may be required based on renal and hepatic function, patient response to therapy (blood sugar levels, HbA1c), and the presence of other medications or medical conditions.
Side Effects
Common Side Effects
- Upper respiratory tract infection, nasopharyngitis, headache, diarrhea, nausea, vomiting, hypoglycemia (especially when combined with other glucose-lowering agents, alcohol use, or missed meals), urinary tract infections, genital fungal infections.
Rare but Serious Side Effects
- Angioedema, acute pancreatitis, lactic acidosis (with metformin), severe hypoglycemia.
Long-Term Effects
- Potential long-term effects need further research, but chronic kidney disease progression is a concern in patients with pre-existing renal issues.
Adverse Drug Reactions (ADR)
- Lactic acidosis, severe hypoglycemia, angioedema, pancreatitis.
Contraindications
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- Severe renal impairment (eGFR < 30 mL/min/1.73m²)
- End-stage renal disease, patients on dialysis
- Hypersensitivity to any component of the medication
Drug Interactions
- Insulin, sulfonylureas (increased risk of hypoglycemia)
- Diuretics (increased risk of dehydration and hypotension)
- Corticosteroids (may increase blood glucose levels)
- Alcohol (increases risk of hypoglycemia and lactic acidosis)
- Medications affecting renal function (may alter the pharmacokinetics of metformin and remogliflozin).
- Carbonic anhydrase inhibitors (e.g., topiramate), cationic drugs eliminated by renal tubular secretion (e.g., digoxin, vancomycin)
Pregnancy and Breastfeeding
- The safety of this combination during pregnancy and breastfeeding has not been established. Should be used only if the potential benefits outweigh the potential risks to the fetus or neonate. Alternative therapies should be considered.
Drug Profile Summary
- Mechanism of Action: See above.
- Side Effects: See above.
- Contraindications: See above.
- Drug Interactions: See above.
- Pregnancy & Breastfeeding: Not established; use with caution.
- Dosage: See above.
- Monitoring Parameters: Blood glucose, HbA1c, renal function, liver function, weight.
Popular Combinations
- This combination itself is a popular combination therapy for type 2 diabetes.
- It may be further combined with insulin in some instances, but this requires careful monitoring due to increased hypoglycemia risk.
Precautions
- Renal and hepatic function should be assessed before and during treatment.
- Monitor for signs and symptoms of hypoglycemia.
- Patient education on diet, exercise, and proper medication adherence is essential.
- Patients should be advised to maintain adequate hydration, especially in hot weather or during strenuous exercise.
- Driving or operating machinery may be affected if dizziness or hypoglycemia occur.
FAQs (Frequently Asked Questions)
A: The typical starting dose is 100mg remogliflozin + 50mg vildagliptin + 500/1000 mg metformin twice daily, taken before meals. Dosages are adjusted based on individual patient needs and responses.
Q2: What are the common side effects?
A: Common side effects include upper respiratory tract infections, nasopharyngitis, headache, diarrhea, nausea, and hypoglycemia.
Q3: Can this medication cause dizziness?
A: Yes, dizziness can occur, especially if blood glucose levels drop too low (hypoglycemia).
Q4: Who should not take this medication?
A: Patients with type 1 diabetes, diabetic ketoacidosis, severe renal impairment, or hypersensitivity to any of the components should not take this medication.
Q5: Does this medication cure diabetes?
A: No, it helps manage blood sugar levels and reduces the risk of complications but doesn’t cure diabetes.
Q6: Is it safe to take this medication during pregnancy?
A: Safety during pregnancy hasn’t been established. Consult a physician to assess the risks and benefits.
Q7: Can I take this medication with other diabetes medications?
A: It may be combined with other medications, such as insulin, but this needs careful monitoring by a doctor due to the increased risk of hypoglycemia. Inform your doctor of all medications you are taking.
Q8: What should I do if I miss a dose?
A: If the next dose is due in more than 12 hours, take the missed dose as soon as possible. If less than 12 hours remain, skip the missed dose and continue with the regular schedule. Do not double the dose.
Q9: What are the long-term effects of taking this medication?
A: Long-term effects are still being investigated, but chronic kidney disease progression is a concern in patients with pre-existing renal issues. Regular monitoring is crucial.
