Usage
- Dapagliflozin + Linagliptin is prescribed for the treatment of type 2 diabetes mellitus in adults. It is used as an adjunct to diet and exercise to improve glycemic control in patients inadequately controlled on metformin monotherapy. It helps lower the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease.
- Pharmacological Classification: Antidiabetic combination, comprised of a sodium-glucose co-transporter 2 (SGLT2) inhibitor (dapagliflozin) and a dipeptidyl peptidase-4 (DPP-4) inhibitor (linagliptin).
- Mechanism of Action: Dapagliflozin increases urinary glucose excretion by inhibiting SGLT2 in the kidneys, thereby lowering blood glucose levels. Linagliptin increases incretin levels (GLP-1 and GIP) by inhibiting DPP-4, which in turn increases insulin secretion and decreases glucagon secretion. The combined effect of both drugs helps in better control of blood sugar levels.
Alternate Names
- No commonly used alternate generic names.
- Brand Names: Qtern, Trajenta Duo
How It Works
- Pharmacodynamics: Dapagliflozin reduces renal glucose reabsorption, leading to glycosuria and lowering blood glucose levels. Linagliptin prolongs the action of incretins, resulting in enhanced glucose-dependent insulin secretion and reduced glucagon secretion. Both contribute to improved glycemic control without increasing insulin resistance.
- Pharmacokinetics:
- Dapagliflozin: Oral bioavailability is 78%. Peak plasma concentration is reached within 2 hours under fasting conditions. High-fat meals can delay and reduce peak concentration but don’t affect overall exposure. Primarily metabolized by glucuronidation; eliminated through urine and feces.
- Linagliptin: Oral bioavailability is approximately 30%. High-fat meals delay peak concentration but don’t impact overall exposure. Primarily metabolized by biliary/fecal excretion with minimal renal elimination.
- Mode of Action: Dapagliflozin inhibits SGLT2 in the renal proximal tubules, preventing glucose reabsorption. Linagliptin inhibits DPP-4 enzyme, preventing incretin degradation.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Dapagliflozin targets SGLT2 receptors. Linagliptin inhibits DPP-4 enzyme.
- Elimination Pathways: Dapagliflozin mainly via biliary/fecal excretion; some renal excretion. Linagliptin predominantly via biliary/fecal excretion, minimal renal elimination.
Dosage
Standard Dosage
Adults:
- Initial: Dapagliflozin 5mg + Linagliptin 5mg once daily in the morning. Can increase to Dapagliflozin 10 mg + Linagliptin 5 mg once daily for additional glycemic control.
- Maximum: Dapagliflozin 10mg + Linagliptin 5mg per day.
- Administration: Oral, can be taken with or without food.
Children:
- Not recommended for use in children under 18 years of age. Safety and effectiveness have not been established.
Special Cases:
- Elderly Patients: Assess renal function and volume status before initiating treatment. Monitor for signs and symptoms of volume depletion.
- Patients with Renal Impairment:
- eGFR 45 mL/min/1.73m² or greater: Standard dosing.
- eGFR 25 to <45 mL/min/1.73m²: Dapagliflozin 10 mg + Linagliptin 5 mg once daily.
- eGFR less than 25 mL/min/1.73m²: Not recommended to initiate; if already on therapy, may continue at 10mg/5mg to reduce risk of eGFR decline and cardiovascular events.
- Dialysis: Contraindicated.
- Patients with Hepatic Dysfunction: No dose adjustment is generally required. However, monitor closely.
- Patients with Comorbid Conditions: Careful assessment of volume status and renal function is essential in patients with cardiovascular disease or those on diuretics. Monitor for signs and symptoms of volume depletion. For patients with a history of pancreatitis, use with caution.
Clinical Use Cases
- Not indicated for use in clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- Dosage adjustments are mainly based on renal function (see “Special Cases: Patients with Renal Impairment”).
Side Effects
Common Side Effects:
- Hypoglycemia (especially with concurrent sulfonylurea or insulin)
- Urinary tract infections
- Genital infections (e.g., vulvovaginitis, balanitis)
- Increased urination
- Nasopharyngitis
- Back pain
- Headache
- Nausea, vomiting, diarrhea
Rare but Serious Side Effects:
- Acute pancreatitis
- Angioedema
- Ketoacidosis (especially in patients with type 1 diabetes)
- Necrotizing fasciitis of the perineum (Fournier’s gangrene)
- Severe hypersensitivity reactions
Long-Term Effects:
- Potential for renal function decline with dapagliflozin, especially in patients with pre-existing renal impairment.
Adverse Drug Reactions (ADR):
Contraindications
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- Severe renal impairment (eGFR <25 mL/min/1.73m²) or dialysis
- History of hypersensitivity to dapagliflozin or linagliptin
Drug Interactions
- Insulin or Sulfonylureas: Increased risk of hypoglycemia. Consider dose reduction of insulin or sulfonylurea.
- Diuretics: Increased risk of volume depletion and hypotension.
- CYP3A4 inducers (e.g., rifampin, phenytoin): May decrease linagliptin levels.
Pregnancy and Breastfeeding
- Pregnancy: Not recommended. May cause fetal harm, especially in the second and third trimesters. Insulin and metformin are safer alternatives.
- Breastfeeding: Not recommended. Dapagliflozin and linagliptin are excreted in rat milk. Potential for neonatal hypoglycemia and effects on kidney development.
Drug Profile Summary
- Mechanism of Action: SGLT2 inhibition (dapagliflozin) and DPP-4 inhibition (linagliptin) leading to reduced blood glucose.
- Side Effects: Hypoglycemia, urinary/genital infections, increased urination.
- Contraindications: Type 1 diabetes, DKA, severe renal impairment, hypersensitivity.
- Drug Interactions: Insulin/sulfonylureas, diuretics, CYP3A4 inducers.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: 5/5 mg to 10/5 mg once daily. Renal adjustments necessary.
- Monitoring Parameters: Blood glucose, HbA1c, renal function, electrolytes, volume status.
Popular Combinations
- Metformin + Dapagliflozin + Linagliptin: For patients not adequately controlled on dual therapy.
Precautions
- General Precautions: Monitor renal function, volume status, and signs of urinary or genital infections.
- Specific Populations: See section on “Dosage: Special Cases” for details on pregnant women, breastfeeding mothers, children and elderly.
- Menstruating Individuals: Vulvovaginitis is a common side effect.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dapagliflozin + Linagliptin?
A: The starting dose is typically Dapagliflozin 5mg + Linagliptin 5mg once daily. It can be increased to Dapagliflozin 10mg + Linagliptin 5mg once daily if needed. Dose adjustments are required for patients with renal impairment.
Q2: Can this combination be used in patients with type 1 diabetes?
A: No, it is contraindicated in type 1 diabetes and diabetic ketoacidosis.
Q3: What are the common side effects?
A: Common side effects include hypoglycemia, urinary tract infections, genital infections, increased urination, and nasopharyngitis.
Q4: Are there any serious side effects to be aware of?
A: Yes, rare but serious side effects include acute pancreatitis, angioedema, and necrotizing fasciitis of the perineum.
Q5: What are the key drug interactions?
A: Important drug interactions occur with insulin, sulfonylureas, and diuretics, potentially increasing the risk of hypoglycemia or hypotension.
Q6: Can it be used during pregnancy or breastfeeding?
A: No, it’s not recommended during pregnancy or while breastfeeding due to potential fetal harm and unknown effects on infants.
Q7: How should I adjust the dose in patients with renal impairment?
A: Dose adjustments are based on eGFR. See the “Dosage” section for specific recommendations.
Q8: What should I monitor in patients taking this medication?
A: Monitor blood glucose, HbA1c, renal function, volume status (especially in patients with CVD or on diuretics), and signs of urinary or genital infections.
Q9: What is the difference between Qtern and Trajenta Duo?
A: Qtern and Trajenta Duo are brand names for the fixed-dose combination of Dapagliflozin and Linagliptin. They contain the same active ingredients and work in the same way.
Q10: Can this drug cause weight loss?
A: Dapagliflozin can contribute to modest weight loss due to increased urinary glucose excretion.
