Usage
- This fixed-dose combination (FDC) medication is prescribed for the treatment of Type 2 Diabetes Mellitus in adults, specifically when diet and exercise alone or in combination with other antidiabetic medications do not provide adequate glycemic control.
- Pharmacological Classification: Antidiabetic; Dual SGLT2 inhibitor (Remogliflozin Etabonate) and DPP-4 inhibitor (Teneligliptin).
- Mechanism of Action: Remogliflozin Etabonate inhibits sodium-glucose cotransporter 2 (SGLT2) in the kidneys, reducing glucose reabsorption and increasing urinary glucose excretion. Teneligliptin inhibits dipeptidyl peptidase-4 (DPP-4), which increases the levels of incretin hormones like GLP-1 and GIP, thereby enhancing insulin secretion and decreasing glucagon secretion. The combined effect lowers both fasting and postprandial blood glucose levels.
Alternate Names
- No widely recognized alternate names exist for this specific combination.
- Brand Names: Zita Plus-R, and other brand names may exist depending on region.
How It Works
- Pharmacodynamics: Remogliflozin Etabonate increases urinary glucose excretion, leading to a reduction in plasma glucose levels. Teneligliptin enhances glucose-dependent insulin secretion and suppresses glucagon secretion, improving glycemic control without promoting weight gain.
- Pharmacokinetics:
- Remogliflozin Etabonate is a prodrug rapidly metabolized to remogliflozin. It is primarily metabolized by CYP3A4, with minor contributions from CYP2C19. It has a short half-life.
- Teneligliptin is metabolized by CYP3A4 and FMO3 and is also excreted unchanged in the urine.
- Due to multiple elimination pathways (renal and hepatic), dosage adjustment is usually not necessary in patients with renal or hepatic impairment.
- Mode of Action: Remogliflozin Etabonate acts on SGLT2 receptors in the renal proximal tubules, blocking glucose reabsorption. Teneligliptin inhibits the DPP-4 enzyme, preventing the degradation of incretin hormones, which in turn modulate pancreatic islet cell function to increase insulin release and decrease glucagon release.
- Elimination Pathways: Remogliflozin is primarily eliminated via hepatic metabolism (CYP3A4), with minor renal excretion. Teneligliptin is eliminated through both renal and hepatic routes (CYP3A4 and FMO3 metabolism, and urinary excretion).
Dosage
Standard Dosage
Adults:
- Initial: 100mg Remogliflozin Etabonate + 20mg Teneligliptin once daily, taken orally after a meal.
- Maintenance: The dose can be adjusted as per the patient’s glycemic response.
Children:
- Not recommended for use in children as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Dose adjustments may be required. Close monitoring for hypoglycemia, renal function, and electrolytes is advised.
- Patients with Renal Impairment: Dosage adjustment is not typically required due to multiple elimination pathways.
- Patients with Hepatic Dysfunction: Dose adjustments may be needed for patients with severe hepatic impairment.
- Patients with Comorbid Conditions: Exercise caution and adjust doses accordingly for those with heart conditions.
Clinical Use Cases
- The combination is not indicated for the mentioned clinical scenarios (Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, Emergency Situations). These settings may necessitate specific insulin regimens and glucose monitoring.
Dosage Adjustments
- Dose adjustment may be necessary based on individual patient response and the presence of comorbidities, particularly renal and hepatic impairment.
Side Effects
Common Side Effects
- Diarrhea
- Nausea
- Vomiting
- Upset stomach
- Headache
- Genital infections (especially in women)
- Urinary tract infections (UTIs)
- Dizziness
- Hypoglycemia (especially when combined with other antidiabetic medications)
Rare but Serious Side Effects
- Acute pancreatitis
- Severe hypoglycemia
- Ketoacidosis
Long-Term Effects
- Chronic kidney disease (with prolonged use in susceptible individuals)
Adverse Drug Reactions (ADR)
- Angioedema (rare)
- Hypersensitivity reactions
Contraindications
- Hypersensitivity to remogliflozin etabonate, teneligliptin, or any component of the formulation.
- Type 1 diabetes mellitus
- Diabetic ketoacidosis (DKA)
- Severe renal impairment (eGFR < 30 mL/min/1.73m²) or end-stage renal disease requiring dialysis
- Severe hepatic impairment
- History of serious hypersensitivity reactions to any SGLT2 or DPP-4 inhibitor
- Pregnancy and breastfeeding
Drug Interactions
- Other antidiabetic medications (e.g., insulin, sulfonylureas): Increased risk of hypoglycemia.
- Diuretics: Increased risk of dehydration and hypotension.
- CYP3A4 inducers or inhibitors: May alter the pharmacokinetics of both remogliflozin and teneligliptin.
- Alcohol: May potentiate hypoglycemia.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not recommended during pregnancy due to potential risks to the fetus.
- Breastfeeding: Not recommended during breastfeeding due to potential risks to the neonate.
Drug Profile Summary
- Mechanism of Action: SGLT2 and DPP-4 inhibition
- Side Effects: Diarrhea, nausea, vomiting, hypoglycemia, UTIs, genital infections
- Contraindications: Type 1 diabetes, DKA, severe renal impairment, pregnancy, breastfeeding
- Drug Interactions: Other antidiabetic agents, diuretics, CYP3A4 inducers/inhibitors
- Pregnancy & Breastfeeding: Not recommended
- Dosage: 100mg/20mg orally once daily after a meal (adjustable as needed)
- Monitoring Parameters: Blood glucose, HbA1c, renal function, electrolytes
Popular Combinations
- Metformin: Often combined with metformin when this combination alone or metformin alone do not provide adequate glycemic control.
Precautions
- General Precautions: Assess renal function, monitor for hypoglycemia, and advise patients on proper hydration. Screen for UTIs and genital infections.
- Specific Populations: Use with caution in patients with hepatic or cardiac impairment. Avoid use during pregnancy and breastfeeding. Not recommended for children.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Remogliflozin Etabonate + Teneligliptin?
A: The initial recommended dosage is 100mg Remogliflozin Etabonate + 20mg Teneligliptin once daily, taken orally after a meal. Dosage may be adjusted based on patient response and clinical assessment.
Q2: How does this combination work in managing blood sugar?
A: It works by reducing glucose reabsorption in the kidneys (Remogliflozin) and by increasing insulin release and reducing glucagon secretion (Teneligliptin), ultimately leading to better blood sugar control.
Q3: What are the common side effects?
A: Common side effects include diarrhea, nausea, vomiting, headache, hypoglycemia, UTIs, and genital infections.
Q4: Is this combination safe for patients with kidney problems?
A: While dose adjustment is usually not necessary for patients with mild to moderate renal impairment, it’s contraindicated in severe renal impairment or end-stage renal disease.
Q5: Can this combination be used during pregnancy or while breastfeeding?
A: No, this combination is contraindicated during pregnancy and breastfeeding due to potential risks to the fetus and neonate.
Q6: What are the major drug interactions to consider?
A: Significant interactions may occur with other antidiabetic medications (increased hypoglycemia risk), diuretics (dehydration risk), and CYP3A4 inducers or inhibitors.
Q7: What precautions should patients be advised about while taking this medication?
A: Patients should maintain adequate hydration, monitor blood sugar regularly, be aware of hypoglycemia symptoms, and report any signs of UTIs or genital infections promptly. They should also limit alcohol intake.
Q8: When should this combination be prescribed?
A: It is typically prescribed for adults with type 2 diabetes when diet, exercise, and other antidiabetic medications (like metformin) haven’t achieved adequate glycemic control.
Q9: Are there any specific monitoring parameters during treatment?
A: Yes, blood glucose levels, HbA1c, renal function, and electrolytes should be monitored regularly.
