Can You Take Januvia and Farxiga Together?
Yes, Januvia (sitagliptin) and Farxiga (dapagliflozin) can be safely taken together and this combination is explicitly supported by clinical trial data and FDA labeling. 1
Evidence for Combination Use
The FDA label for dapagliflozin specifically describes a clinical trial evaluating dapagliflozin in combination with sitagliptin, demonstrating this is an approved and studied combination. 1 In this 24-week placebo-controlled trial of 452 patients, dapagliflozin 10 mg plus sitagliptin 100 mg (with or without metformin) provided statistically significant improvements in HbA1c, fasting plasma glucose, and body weight compared to sitagliptin alone. 1
Complementary Mechanisms of Action
These two medications work through entirely different mechanisms, making them ideal combination partners:
Sitagliptin (DPP-4 inhibitor): Increases endogenous GLP-1 levels by preventing its breakdown, enhancing glucose-dependent insulin secretion and inhibiting glucagon secretion 2
Dapagliflozin (SGLT2 inhibitor): Promotes urinary glucose excretion by inhibiting renal glucose reabsorption, independent of insulin 2
Clinical Benefits of the Combination
Glycemic control: The combination provides additive glucose-lowering effects through complementary pathways. 1, 3 Real-world data from 358 Indian patients showed significant HbA1c reduction from 8.9% to 7.2% after 12 weeks of dapagliflozin-sitagliptin combination therapy. 3
Low hypoglycemia risk: Neither medication stimulates insulin secretion in a glucose-independent manner, so hypoglycemia risk remains low when used together without sulfonylureas or insulin. 2
Cardiovascular and renal protection: SGLT2 inhibitors like dapagliflozin provide proven cardiovascular and kidney benefits independent of glucose lowering, which DPP-4 inhibitors do not compromise. 2
Weight and blood pressure: Dapagliflozin promotes modest weight loss and blood pressure reduction, while sitagliptin is weight-neutral. 2, 1
Dosing Considerations
Standard dosing: Sitagliptin 100 mg once daily plus dapagliflozin 10 mg once daily is the typical regimen. 1
Renal adjustments required:
- Sitagliptin: Reduce to 50 mg daily if eGFR 30-44 mL/min/1.73m²; reduce to 25 mg daily if eGFR <30 mL/min/1.73m² 2
- Dapagliflozin: Can initiate at 10 mg daily if eGFR ≥25 mL/min/1.73m²; do not initiate if eGFR <25 mL/min/1.73m² (though may continue if already established for heart failure/kidney benefits until dialysis) 2
Safety Monitoring
Renal function: Check eGFR at baseline and monitor at least annually if eGFR ≥60 mL/min/1.73m², or every 3-6 months if eGFR 30-59 mL/min/1.73m². 2
SGLT2 inhibitor-specific risks:
- Genital mycotic infections (6% vs 1% placebo): Counsel on daily genital hygiene 2
- Volume depletion: Monitor for hypovolemia, especially in patients on diuretics 2
- Euglycemic diabetic ketoacidosis: Educate patients to discontinue during acute illness and seek immediate care for nausea, vomiting, or abdominal pain 2
DPP-4 inhibitor considerations: Sitagliptin has shown cardiovascular safety (no increased risk) in outcome trials, unlike saxagliptin which increases heart failure risk. 2
Common Pitfalls to Avoid
Do not avoid this combination due to concerns about "polypharmacy": The mechanisms are complementary and the combination is evidence-based. 1, 3
Do not discontinue dapagliflozin for initial eGFR dip: An initial decline of 3-5 mL/min/1.73m² is expected and hemodynamically mediated, with long-term nephroprotective benefits. 2
Do not withhold SGLT2 inhibitors waiting for "target HbA1c": Cardiovascular and renal benefits are independent of glucose lowering and should be initiated based on comorbidities (heart failure, CKD, cardiovascular disease), not just glycemic control. 2
Implement sick day protocol: Instruct patients to temporarily discontinue dapagliflozin during acute illness, dehydration, or reduced oral intake to minimize ketoacidosis and volume depletion risks. 2