Titration Schedule for Empagliflozin and Semaglutide in Type 2 Diabetes

Initiation and Titration

The American College of Cardiology recommends initiating empagliflozin at 10 mg orally once daily, which provides optimal cardiovascular and glycemic benefits with a favorable safety profile 1, 2
No dose titration is required for cardiovascular or renal risk reduction benefits with empagliflozin 2
The American Diabetes Association suggests that if additional glycemic control is needed, the dose of empagliflozin may be increased to 25 mg once daily, though this provides only additional glucose-lowering benefits without additional cardiovascular protection 2
Empagliflozin can be taken at any time of day, with or without food, as recommended by the American College of Cardiology 1
Semaglutide should be initiated at 0.25 mg subcutaneously once weekly for 4 weeks, as recommended by the Mayo Clinic 4
After 4 weeks on the 0.25 mg dose, the dose of semaglutide should be increased to 0.5 mg once weekly, according to the Mayo Clinic 4
If additional glycemic control is required, the dose of semaglutide can be increased to 1 mg once weekly after 4 weeks of treatment with the 0.5 mg dose, as suggested by the Mayo Clinic 4

For patients with eGFR ≥45 mL/min/1.73 m², no dose adjustment is required for empagliflozin, according to the Journal of the American College of Cardiology 3, 1
For patients with eGFR <45 mL/min/1.73 m², empagliflozin is not recommended for glycemic control, though it may still be used for cardiovascular or renal benefits, as recommended by the American College of Cardiology 1, 2
Empagliflozin is contraindicated in patients with severe renal impairment (eGFR <20 mL/min/1.73 m²) or those on dialysis, according to the American College of Cardiology 1, 2
No dosage adjustments are required for semaglutide based on renal function, as recommended by the Mayo Clinic 4
Semaglutide can be used in patients with renal impairment, including those with end-stage renal disease, according to the Mayo Clinic 4

When initiating empagliflozin, consider reducing or stopping sulfonylureas/glinides or reducing total daily insulin dose by approximately 20% to prevent hypoglycemia, as recommended by the American Diabetes Association 2
Discontinue empagliflozin at least 3 days before planned surgery to prevent postoperative ketoacidosis, according to the American College of Cardiology 1, 2
Monitor for genital mycotic infections and urinary tract infections, which occur more frequently with SGLT2 inhibitors, as recommended by the American College of Cardiology 1
Not adjusting concomitant diabetes medications (especially insulin or sulfonylureas) when starting either medication increases hypoglycemia risk, according to the American Diabetes Association 2
Forgetting to discontinue empagliflozin before surgical procedures increases ketoacidosis risk, as recommended by the American College of Cardiology 1, 2