Usage
Dapagliflozin + Sitagliptin is prescribed as an adjunct to diet and exercise for improving glycemic control in adults with type 2 diabetes mellitus. It is specifically indicated when treatment with both dapagliflozin and sitagliptin is deemed appropriate by a healthcare professional. It is generally used in combination with metformin unless metformin is contraindicated or not tolerated by the patient.
This fixed-dose combination falls under the pharmacological classification of antidiabetic agents, encompassing two distinct drug classes:
- Dapagliflozin: Sodium-glucose co-transporter-2 (SGLT2) inhibitor
- Sitagliptin: Dipeptidyl peptidase-4 (DPP-4) inhibitor
The mechanism of action involves two complementary pathways: Dapagliflozin works by blocking glucose reabsorption in the kidneys, increasing urinary glucose excretion, and thereby lowering blood glucose levels. Sitagliptin works by increasing incretin levels (GLP-1 and GIP), which in turn stimulates insulin release and suppresses glucagon secretion, further contributing to blood glucose control.
Alternate Names
While “Dapagliflozin + Sitagliptin” represents the generic name, this combination is marketed under brand names like Qtern, Sidapvia, and Zitaneo-Dapa 100/10.
How It Works
Pharmacodynamics:
Dapagliflozin inhibits SGLT2 in the kidneys, preventing glucose reabsorption and promoting urinary glucose excretion. Sitagliptin inhibits DPP-4, the enzyme responsible for degrading incretin hormones like GLP-1 and GIP. This leads to increased incretin levels, promoting insulin secretion (especially postprandially) and suppressing glucagon secretion, contributing to improved glycemic control.
Pharmacokinetics:
- Absorption: Both drugs are orally administered and well-absorbed. Food does not significantly impact the absorption of either drug.
- Metabolism: Dapagliflozin is primarily metabolized through UGT1A9-mediated glucuronidation, with its major metabolite (dapagliflozin 3-O-glucuronide) being inactive. Sitagliptin is primarily excreted unchanged in the urine, with a small fraction metabolized hepatically.
- Elimination: Dapagliflozin is primarily eliminated renally (75% as dapagliflozin and its metabolites), with the remainder eliminated in feces. Sitagliptin is mainly eliminated renally (87%), with a small fraction eliminated in feces.
Mode of Action:
- Dapagliflozin: Binds to and inhibits SGLT2 in the proximal renal tubules, reducing renal glucose reabsorption. This results in increased urinary glucose excretion, lowering blood glucose levels independently of insulin secretion.
- Sitagliptin: Inhibits DPP-4, the enzyme that degrades incretin hormones (GLP-1 and GIP). This inhibition increases the circulating levels of these hormones, which then stimulate glucose-dependent insulin secretion from pancreatic beta-cells and suppress glucagon secretion from alpha-cells, contributing to improved glycemic control.
Dosage
Standard Dosage
Adults:
The recommended starting dose is Dapagliflozin 5 mg + Sitagliptin 50 mg once daily, taken orally. For additional glycemic control, the dose may be increased to Dapagliflozin 10 mg + Sitagliptin 100 mg once daily.
Children:
The safety and efficacy in children below 10 years of age haven’t been established. For children aged 10 years and above, similar dosing to adults applies, starting with the lower dose and adjusting based on glycemic control and tolerability.
Special Cases:
- Elderly Patients: No specific dose adjustment is recommended based solely on age. However, renal function should be assessed before and during treatment.
- Patients with Renal Impairment: For patients with eGFR <45 mL/min/1.73 m², the use of this combination is not recommended. Individual components should be considered at adjusted doses or alternative therapies.
- Patients with Hepatic Dysfunction: For mild to moderate hepatic impairment, no dose adjustment is needed. In severe hepatic impairment, a lower starting dose is recommended, titrating upwards based on tolerability.
- Patients with Comorbid Conditions: Individualized dosage adjustments might be necessary based on other medical conditions and concurrent medications.
Clinical Use Cases
The provided sources do not provide details of clinical use cases involving Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, or Emergency Situations. Therefore, dosage recommendations specific to those settings can’t be addressed here.
Dosage Adjustments
Dosage modifications are necessary for patients with renal impairment, and in those with severe hepatic dysfunction.
Side Effects
Common Side Effects
- Genital mycotic infections (e.g., vulvovaginitis, balanitis)
- Urinary tract infections (UTIs)
- Nasopharyngitis
- Upper respiratory tract infections
- Headache
- Diarrhea
- Hypoglycemia (especially when combined with other antidiabetic medications)
- Nausea
- Vomiting
Rare but Serious Side Effects
- Diabetic ketoacidosis (DKA), especially in patients with type 1 diabetes or during acute illness
- Acute pancreatitis
- Hypersensitivity reactions (e.g., anaphylaxis, angioedema)
- Severe renal impairment or acute kidney injury
- Necrotizing fasciitis of the perineum (Fournier’s gangrene)
Long-Term Effects
- Potential for chronic complications related to diabetes or other underlying conditions.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include hypersensitivity reactions, DKA, acute pancreatitis, severe renal impairment, and Fournier’s gangrene. These require immediate medical intervention.
Contraindications
- Hypersensitivity to dapagliflozin or sitagliptin
- Type 1 diabetes mellitus
- Severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease (ESRD)
- Patients on dialysis
Drug Interactions
- Insulin and Insulin Secretagogues (e.g., sulfonylureas): Increased risk of hypoglycemia; dose adjustments of insulin or sulfonylureas may be required.
- Diuretics (e.g., furosemide, hydrochlorothiazide): Enhanced diuretic effect and increased risk of dehydration and hypotension.
- Alcohol: Increased risk of hypoglycemia and other adverse effects.
Pregnancy and Breastfeeding
Dapagliflozin + Sitagliptin is generally not recommended during pregnancy and breastfeeding due to limited safety data. If a patient becomes pregnant while taking this combination, alternative therapies should be considered. Consult a healthcare professional for case-specific advice.
Drug Profile Summary
- Mechanism of Action: Dapagliflozin (SGLT2 inhibitor) increases urinary glucose excretion; Sitagliptin (DPP-4 inhibitor) enhances incretin levels, increasing insulin secretion and reducing glucagon secretion.
- Side Effects: Common: Genital infections, UTIs, nasopharyngitis, headache, diarrhea, hypoglycemia. Serious: DKA, acute pancreatitis, hypersensitivity, renal impairment.
- Contraindications: Hypersensitivity, type 1 diabetes, severe renal impairment, dialysis.
- Drug Interactions: Insulin/sulfonylureas, diuretics, alcohol.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: Dapagliflozin 5-10 mg + Sitagliptin 50-100 mg once daily. Children (≥10 years): Similar to adult dosing.
- Monitoring Parameters: Blood glucose levels, renal function, HbA1c.
Popular Combinations
A popular combination is Dapagliflozin + Sitagliptin + Metformin, especially when dual therapy is insufficient for glycemic control. Metformin enhances insulin sensitivity and reduces hepatic glucose production, complementing the actions of dapagliflozin and sitagliptin.
Precautions
- Monitor renal function, blood glucose, HbA1c, and volume status.
- Assess for signs of DKA, acute pancreatitis, hypersensitivity, and UTIs.
- Caution in patients with history of pancreatitis, renal or hepatic impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dapagliflozin + Sitagliptin?
A: The starting dose is Dapagliflozin 5 mg + Sitagliptin 50 mg once daily. It can be increased to 10 mg + 100 mg once daily if needed for additional glycemic control.
Q2: How does this combination work to lower blood sugar?
A: Dapagliflozin removes glucose through urine, and sitagliptin helps the body release more insulin and less glucagon.
Q3: Who shouldn’t take this medication?
A: Individuals with type 1 diabetes, severe kidney problems, or dialysis shouldn’t take this medication.
Q4: Are there any serious side effects I should be aware of?
A: Yes, rare but serious side effects include a severe pancreatic condition, allergic reactions, kidney problems, and a specific genital infection. Seek immediate medical help if these occur.
Q5: Can I take this medication if I’m pregnant or breastfeeding?
A: It’s generally not recommended. Consult your doctor.
Q6: What other medications might interact with this combination?
A: Medications like insulin, water pills, and alcohol can interact. Inform your doctor about all your medications.
Q7: Should I continue taking this medication if my blood sugar improves?
A: Do not stop without talking to your doctor, as stopping suddenly can cause your blood sugar to rise again.
Q8: What if I have mild or moderate liver problems?
A: You likely won’t need a dose adjustment, but your doctor should be aware of your liver condition.
Q9: What lifestyle changes should I make while on this medication?
A: Healthy eating, regular exercise, and weight management remain crucial for managing your diabetes even while taking medication.
