Usage
- Metformin + Remogliflozin Etabonate is prescribed for the treatment of type 2 diabetes mellitus in adults, as an adjunct to diet and exercise. It is indicated for patients insufficiently controlled on their maximally tolerated dose of Metformin alone or in patients already being treated with the combination of Remogliflozin and Metformin as separate tablets. It is not indicated for type 1 diabetes mellitus.
- Pharmacological Classification: Antidiabetic combination; Biguanide (Metformin) + Sodium-glucose co-transporter-2 (SGLT2) inhibitor (Remogliflozin Etabonate).
- Mechanism of Action: This combination medication works through two distinct mechanisms:
- Metformin: Decreases hepatic glucose production, reduces intestinal glucose absorption, and improves insulin sensitivity.
- Remogliflozin Etabonate: Inhibits SGLT2 in the kidneys, blocking glucose reabsorption and promoting urinary glucose excretion.
Alternate Names
- No widely used alternate names.
- Brand Names: Remo-M, Reniva M, and others (brand names vary regionally).
How It Works
- Pharmacodynamics:
- Metformin lowers blood glucose levels by reducing hepatic glucose production, decreasing intestinal glucose absorption, and increasing insulin sensitivity in peripheral tissues. It does not stimulate insulin secretion.
- Remogliflozin Etabonate lowers blood glucose levels by increasing urinary glucose excretion. It inhibits SGLT2 in the renal proximal tubules, preventing reabsorption of filtered glucose back into the bloodstream.
- Pharmacokinetics:
- Metformin: Absorbed from the gastrointestinal tract, not metabolized significantly, and excreted primarily by the kidneys.
- Remogliflozin Etabonate: Absorbed after oral administration, metabolized primarily by glucuronidation, and eliminated in urine and feces. It does not inhibit or induce CYP450 enzymes.
- Mode of Action (Cellular/Molecular):
- Metformin’s precise mechanism is complex and not fully understood but appears to involve activation of AMP-activated protein kinase (AMPK).
- Remogliflozin Etabonate selectively inhibits SGLT2, a low-affinity, high-capacity glucose transporter responsible for the majority of renal glucose reabsorption.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation:
- Metformin activates AMPK.
- Remogliflozin Etabonate inhibits SGLT2.
- Elimination Pathways:
- Metformin: Renal excretion.
- Remogliflozin Etabonate: Primarily renal excretion of glucuronide metabolites, partially fecal excretion.
Dosage
Standard Dosage
Adults:
- Starting dose is typically Remogliflozin 100mg + Metformin 500mg twice daily.
- The dose may be adjusted based on individual glycemic control up to a maximum of Remogliflozin 100mg + Metformin 1000mg twice daily.
Children:
- Not recommended for use in children under 18 years of age, as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Initiate at a lower dose and titrate cautiously based on renal function and glycemic response.
- Patients with Renal Impairment: Contraindicated in patients with moderate to severe renal impairment (eGFR < 60 mL/min). Dosage adjustment is needed for mild renal impairment.
- Patients with Hepatic Dysfunction: Not recommended for use in patients with moderate to severe hepatic impairment. Caution should be exercised in patients with mild hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in patients with diabetic ketoacidosis, history of lactic acidosis, or severe cardiovascular disease.
Clinical Use Cases
- Not specifically indicated for use in intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Standard diabetic management protocols apply in these settings.
Dosage Adjustments
- Adjust dose based on patient-specific factors such as renal function, hepatic function, and concomitant medications.
Side Effects
Common Side Effects
- Hypoglycemia, urinary tract infections, genital mycotic infections, nausea, vomiting, increased urination, stomach upset.
Rare but Serious Side Effects
- Lactic acidosis (Metformin), diabetic ketoacidosis, severe hypoglycemia, acute pancreatitis, necrotizing fasciitis of the perineum (Fournier’s gangrene).
Long-Term Effects
- Vitamin B12 deficiency (Metformin).
Adverse Drug Reactions (ADR)
- Angioedema, hypersensitivity reactions.
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 Metformin or Remogliflozin Etabonate, acute or chronic metabolic acidosis, including lactic acidosis.
Drug Interactions
- Carbonic anhydrase inhibitors (e.g., topiramate, acetazolamide), cationic drugs eliminated by renal tubular secretion (e.g., digoxin, vancomycin), diuretics (e.g., furosemide), insulin, insulin secretagogues (e.g., sulfonylureas), alcohol.
- CYP450 interactions are not expected as remogliflozin does not inhibit or induce CYP450 enzymes.
Pregnancy and Breastfeeding
- Pregnancy: Limited data available. Use only if clearly needed and the potential benefit outweighs the potential risk to the fetus.
- Breastfeeding: Limited data available. Not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Metformin reduces hepatic glucose production and increases insulin sensitivity; Remogliflozin increases urinary glucose excretion.
- Side Effects: Hypoglycemia, UTI, genital infections, nausea, vomiting.
- Contraindications: Type 1 diabetes, DKA, renal impairment, acidosis.
- Drug Interactions: Diuretics, insulin secretagogues, alcohol.
- Pregnancy & Breastfeeding: Consult physician; use with caution.
- Dosage: Adults: Start with 100mg/500mg BID, adjust based on glycemic control.
- Monitoring Parameters: HbA1c, fasting and postprandial glucose, renal function, electrolytes.
Popular Combinations
- Metformin + Remogliflozin Etabonate + Vildagliptin.
Precautions
- Monitor renal function.
- Risk of hypoglycemia, especially with insulin or sulfonylureas.
- Maintain adequate hydration.
FAQs (Frequently Asked Questions)
A: The typical starting dose is 100mg Remogliflozin + 500mg Metformin twice daily, adjusted as needed up to a maximum of 100mg Remogliflozin + 1000mg Metformin twice daily.
A: This combination targets multiple pathways involved in glucose regulation, offering synergistic effects in lowering blood glucose.
Q3: Can this drug be used in patients with renal impairment?
A: It’s contraindicated in moderate to severe renal impairment. Dose adjustment is needed in mild impairment. Closely monitor renal function.
Q4: What are the common side effects patients should be aware of?
A: Hypoglycemia, urinary tract infections, genital mycotic infections, nausea, increased urination are common side effects.
Q5: Are there any specific monitoring parameters for this medication?
A: Yes, monitor HbA1c, fasting and postprandial blood glucose, renal function, and electrolytes.
Q6: Can this combination be used during pregnancy or breastfeeding?
A: Limited safety data is available. Consult a physician; use with caution if the benefits outweigh the risks.
Q7: How should a missed dose be managed?
A: Take the missed dose as soon as remembered unless it’s near the next dose. Don’t double the dose.
Q8: What should be done in case of suspected lactic acidosis?
A: Discontinue the medication immediately and seek immediate medical attention. Lactic acidosis is a rare but serious side effect of metformin.
Q9: Can patients drink alcohol while taking this medicine?
A: Alcohol should be avoided or consumed in moderation, as it may increase the risk of hypoglycemia and other side effects.
Q10: Does food affect the absorption of this medicine?
A: The provided research does not mention a significant effect of food on drug efficacy. However, taking this medicine with meals can lessen gastrointestinal issues.
