Vildagliptin Dose Adjustment with Metformin
No dose adjustment is needed for vildagliptin when combined with metformin in patients with normal renal function, but vildagliptin requires dose reduction to 50 mg once daily (from the standard 100 mg daily) in patients with moderate or severe renal impairment (eGFR <50 mL/min/1.73m²), regardless of metformin use. 1, 2
Drug Interaction Considerations
- Vildagliptin and metformin can be coadministered without dose adjustment for either agent based on drug-drug interaction alone. 2
- Coadministration causes only minor pharmacokinetic changes: an 18% decrease in vildagliptin peak concentration and a 15% increase in metformin exposure, neither of which is clinically significant. 2
- The combination is well-tolerated with no serious adverse events related to the drug interaction itself. 2, 3
Renal Function-Based Dosing Algorithm
For Patients with eGFR ≥60 mL/min/1.73m²
- Use standard vildagliptin dosing of 50 mg twice daily (100 mg total daily dose). 1
- Continue metformin at standard doses without adjustment. 4
- Monitor renal function at least annually. 5
For Patients with eGFR 45-59 mL/min/1.73m²
- Reduce vildagliptin to 50 mg once daily. 1
- Continue current metformin dose but avoid increasing it; consider dose reduction in elderly patients or those with liver disease. 4
- Monitor renal function every 3-6 months. 4, 5
For Patients with eGFR 30-44 mL/min/1.73m² (Moderate Renal Impairment)
- Reduce vildagliptin to 50 mg once daily. 1
- Reduce metformin to half the maximum dose (maximum 1000 mg daily, typically 500 mg twice daily). 4
- Monitor renal function every 3-6 months. 4
For Patients with eGFR <30 mL/min/1.73m² (Severe Renal Impairment)
- Reduce vildagliptin to 50 mg once daily. 6, 1
- Discontinue metformin immediately—it is contraindicated. 4
- Vildagliptin remains effective and safe in this population, particularly when combined with insulin. 6
Clinical Efficacy in Renal Impairment
- Vildagliptin 50 mg once daily in patients with severe renal impairment (eGFR <30 mL/min/1.73m²) reduces HbA1c by approximately 0.9%, with 45% of patients achieving HbA1c <7.0%. 6
- The drug maintains comparable hypoglycemic risk to placebo and causes no weight gain, even in difficult-to-treat populations with longstanding diabetes and severe renal impairment. 6
Safety Profile with Metformin Combination
- In patients with mild renal impairment (eGFR 50-80 mL/min/1.73m²), vildagliptin as add-on to metformin shows lower rates of study discontinuation due to adverse events compared to thiazolidinediones. 7
- Common adverse events include headache and rash, but serious adverse events are rare (1.6-2.4%). 7
- The combination does not increase hypoglycemia risk and is weight-neutral. 6, 3
Critical Monitoring Requirements
- Assess renal function before initiating vildagliptin and adjust dose accordingly. 1
- For patients on metformin with eGFR <60 mL/min/1.73m², monitor renal function every 3-6 months. 4, 5
- Implement "sick day rules" to temporarily stop metformin during acute illness that could cause acute kidney injury. 5
- Monitor vitamin B12 levels in patients on metformin for >4 years. 4, 5
Common Pitfalls to Avoid
- Do not continue standard vildagliptin dosing (100 mg daily) in patients with any degree of renal impairment (eGFR <50 mL/min/1.73m²)—always reduce to 50 mg once daily. 1
- Do not continue metformin when eGFR falls below 30 mL/min/1.73m²—this is an absolute contraindication due to lactic acidosis risk. 4
- Do not assume that because vildagliptin and metformin can be combined without interaction-based dose adjustment, renal function-based adjustments are unnecessary—they are mandatory. 1, 2