Can Patients Take Jardiance and Januvia Together?
Yes, patients can safely take Jardiance (empagliflozin) and Januvia (sitagliptin) together—this combination is well-established, pharmacologically complementary, and does not require dose adjustments for either medication. 1, 2
Pharmacokinetic Safety and Drug Interactions
No clinically significant drug-drug interactions exist between empagliflozin and sitagliptin. A randomized crossover study in healthy volunteers demonstrated that coadministration did not meaningfully alter the area under the curve (AUC) or maximum plasma concentrations (Cmax) of either drug, with geometric mean ratios remaining within acceptable bioequivalence ranges. 2
Both medications can be administered at their standard doses without adjustment: empagliflozin 10-25 mg once daily and sitagliptin 100 mg once daily (or dose-adjusted for renal function). 1, 2
Complementary Mechanisms of Action
Empagliflozin (SGLT2 inhibitor) works by blocking renal glucose reabsorption, promoting urinary glucose excretion independent of insulin, while also providing cardiovascular and renal protective benefits. 3, 4
Sitagliptin (DPP-4 inhibitor) enhances glucose-dependent insulin secretion by increasing endogenous GLP-1 levels and inhibiting glucagon secretion, working through an insulin-dependent mechanism. 1, 4
The combination provides additive glucose-lowering effects because the mechanisms target different pathophysiologic defects in type 2 diabetes—renal glucose handling versus incretin enhancement. 1, 4
Clinical Benefits of Combination Therapy
Low hypoglycemia risk: Both agents have minimal intrinsic hypoglycemia risk when used together, as neither directly stimulates insulin secretion in a glucose-independent manner. 1, 4
Cardiovascular and renal protection: Empagliflozin provides proven cardiovascular mortality reduction and heart failure benefits, while sitagliptin has demonstrated cardiovascular safety (unlike saxagliptin, which increases heart failure risk). 1, 3
Weight and blood pressure benefits: Empagliflozin promotes modest weight loss (approximately 2 kg) and blood pressure reduction (systolic approximately 4 mmHg), while sitagliptin remains weight-neutral. 1, 3
Renal Function Considerations
Sitagliptin requires dose reduction based on eGFR: Reduce to 50 mg daily if eGFR 30-44 mL/min/1.73m², and to 25 mg daily if eGFR <30 mL/min/1.73m². 1
Empagliflozin can be initiated if eGFR ≥25 mL/min/1.73m² but should not be started if eGFR <25 mL/min/1.73m². Note that empagliflozin's glucose-lowering efficacy decreases with declining renal function, though cardiovascular and renal benefits persist. 1, 3
Monitor renal function at baseline and at least annually if eGFR ≥60 mL/min/1.73m², or every 3-6 months if eGFR 30-59 mL/min/1.73m². 1
Safety Monitoring and Common Pitfalls
Counsel patients on daily genital hygiene to reduce the risk of mycotic genital infections associated with empagliflozin, which occur more frequently in women. 1, 3
Monitor for volume depletion and euglycemic diabetic ketoacidosis, particularly in patients with poor oral intake, on diuretics, or with intercurrent illness. 1
If the patient is also taking insulin or sulfonylureas, be aware that hypoglycemia risk increases—consider reducing insulin doses by 10-20% or discontinuing/reducing sulfonylureas when initiating this combination. 5, 1
Clinical Positioning
This combination is appropriate as dual therapy in patients not controlled on metformin alone, or as triple therapy when added to metformin. 6, 4
DPP-4 inhibitors like sitagliptin are well-tolerated in hospitalized patients with mild-to-moderate hyperglycemia (glucose <180 mg/dL), though routine use of SGLT2 inhibitors in the hospital is not recommended due to ketoacidosis risk. 5
The combination is particularly valuable in patients with established cardiovascular disease or chronic kidney disease, where empagliflozin provides additional organ protection beyond glucose lowering. 1