Is sitagliptin (Januvia) 25mg once daily an appropriate substitute for Jardiance (empagliflozin) 25mg once daily to maintain the same blood glucose levels?

Sitagliptin 25 mg is NOT an appropriate substitute for Jardiance 25 mg

Sitagliptin 25 mg once daily cannot maintain the same blood glucose levels as empagliflozin (Jardiance) 25 mg, and more importantly, you would be eliminating critical cardiovascular and renal protective benefits that empagliflozin provides. 1

Key Differences in Efficacy and Outcomes

Glycemic Control

• SGLT2 inhibitors like empagliflozin have "high to very high" glucose-lowering efficacy, while DPP-4 inhibitors like sitagliptin have only "intermediate" efficacy 1
• Sitagliptin monotherapy reduces HbA1c by approximately 0.5-0.8% 2, 3, which is generally less than what empagliflozin achieves at 25 mg daily
• The 25 mg dose of sitagliptin you're proposing is a reduced dose used only for severe renal impairment (eGFR 15-29 mL/min/1.73 m²) 1, not for standard glycemic control, making it even less effective

Critical Cardiovascular and Renal Benefits Lost

This is the most important consideration:

• Empagliflozin provides proven cardiovascular mortality reduction and heart failure benefits that sitagliptin does not offer 1
• Empagliflozin provides proven renal protection, slowing eGFR decline and reducing albuminuria 1
• Sitagliptin shows "neutral" effects on cardiovascular outcomes, heart failure, and renal outcomes 1
• If the patient was prescribed Jardiance 25 mg, there was likely a clinical indication beyond glucose control alone (cardiovascular disease, heart failure, or chronic kidney disease) 1

Mechanism of Action Differences

These medications work through completely different mechanisms:

• Empagliflozin: Blocks glucose reabsorption in the kidney, causing glucose excretion in urine, with additional hemodynamic and metabolic benefits 1
• Sitagliptin: Enhances incretin hormone activity to stimulate insulin secretion in a glucose-dependent manner 2, 4

You cannot expect equivalent glucose control from fundamentally different mechanisms, especially at a reduced sitagliptin dose. 1

Clinical Algorithm for Discontinuing Empagliflozin

If empagliflozin must be discontinued, the appropriate substitute depends on why it's being stopped:

If stopping due to side effects (e.g., genital infections, volume depletion):

• First choice: GLP-1 receptor agonist (dulaglutide, liraglutide, or semaglutide) - provides cardiovascular and renal benefits similar to SGLT2 inhibitors 1
• Second choice: Another SGLT2 inhibitor (dapagliflozin or canagliflozin) if the side effect was specific to empagliflozin 1

If stopping due to renal function decline:

• Continue empagliflozin if eGFR ≥20 mL/min/1.73 m² for ongoing cardiovascular and renal protection, even though glucose-lowering efficacy diminishes 1
• Switch to GLP-1 receptor agonist if empagliflozin must be stopped 1

If stopping due to cost or access issues:

• Advocate for patient assistance programs for empagliflozin or alternative SGLT2 inhibitors first 1
• GLP-1 receptor agonist remains the preferred alternative 1

Why Sitagliptin Should NOT Be the Choice

Sitagliptin would only be appropriate as add-on therapy if the patient needs additional glucose lowering while continuing empagliflozin 1, not as a replacement. The 2025 ADA guidelines clearly position DPP-4 inhibitors as having neutral effects on the outcomes that matter most: mortality, cardiovascular events, heart failure, and renal progression 1.

Common Pitfall to Avoid

Do not make medication substitutions based solely on glucose-lowering equivalence. Modern diabetes management prioritizes cardiovascular and renal outcomes over HbA1c reduction alone 1. Switching from an SGLT2 inhibitor to a DPP-4 inhibitor eliminates proven mortality and morbidity benefits, even if glucose levels appear similar 1.