Regulatory Decision Summary for Synjardy

Empagliflozin and metformin are approved anti hyperglycemic medications for adults with Type 2 diabetes mellitus and are already indicated for co-administration to improve glycemic control when metformin alone is inadequate, at a maximum daily dose of 25 milligrams (mg) for empagliflozin and 2550 mg of metformin.

The FDC of empagliflozin/metformin tablets is proposed at different dosage strengths which fit within the already proposed dosage (5mg or 12,5 mg of empagliflozin, each dose with 500 mg, 850 mg or 1000 mg metformin).

Bioequivalence was established for the empagliflozin/metformin FDC tablet at all proposed marketed strengths.

A relative bioavailability study confirmed that the overall systemic exposure to empagliflozin was similar between twice daily (BID) and once daily (QD) dosing, with similar pharmacodynamic effects to inhibit renal reabsorption of glucose.

A Phase 2B trial supported BID dosing of empagliflozin as an add-on therapy to metformin. Statistically significant improvements in the primary efficacy endpoint (reduction in HbA1c) and secondary efficacy endpoints (such as reduction in fasting plasma glucose) were observed.

The safety profile of Synjardy tablets is consistent with the safety profiles of its individual components (diabetic ketoacidosis, kidney injury, volume depletion, elevated hemoglobin and hematocrit, genital mycotic infections and urinary tract infections for empagliflozin; hypoglycemia and lactic acidosis for metformin). Risk is mitigated with appropriate labelling.

The overall benefit-harm-uncertainty risk is favourable.