What is the recommended titration schedule for empagliflozin (Jardiance) and semaglutide (Ozempic) in patients with type 2 diabetes?

Titration Schedule for Empagliflozin and Semaglutide in Type 2 Diabetes

For patients with type 2 diabetes, empagliflozin should be initiated at 10 mg once daily without need for titration, while semaglutide should be started at 0.25 mg once weekly and titrated gradually to 1 mg over 8 weeks.

Empagliflozin (Jardiance) Titration

• Initiate 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 2
• If additional glycemic control is needed, the dose 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 1

Renal Considerations for Empagliflozin

• For patients with eGFR ≥45 mL/min/1.73 m², no dose adjustment is required 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 1, 2
• Empagliflozin is contraindicated in patients with severe renal impairment (eGFR <20 mL/min/1.73 m²) or those on dialysis 1, 2

Special Considerations for Empagliflozin

• When initiating empagliflozin, consider reducing or stopping sulfonylureas/glinides or reducing total daily insulin dose by approximately 20% to prevent hypoglycemia 2
• Discontinue empagliflozin at least 3 days before planned surgery to prevent postoperative ketoacidosis 1, 2
• Monitor for genital mycotic infections and urinary tract infections, which occur more frequently with SGLT2 inhibitors 1

Semaglutide (Ozempic) Titration

• Initiate semaglutide at 0.25 mg subcutaneously once weekly for 4 weeks 3
• After 4 weeks on the 0.25 mg dose, increase to 0.5 mg once weekly 3
• If additional glycemic control is required, can increase to 1 mg once weekly after 4 weeks of treatment with the 0.5 mg dose 3
• Semaglutide can be administered at any time of day, with or without meals 3

Renal Considerations for Semaglutide

• No dosage adjustments are required for semaglutide based on renal function 3
• Semaglutide can be used in patients with renal impairment, including those with end-stage renal disease 3

Special Considerations for Semaglutide

• The gradual dose escalation of semaglutide is designed to minimize gastrointestinal side effects, which are the most common adverse events 4, 5
• Gastrointestinal disorders, most commonly nausea, are the most frequently reported adverse events with semaglutide, occurring in up to 47% of patients 4
• If a patient experiences significant gastrointestinal side effects, consider maintaining the current dose before increasing to the next dose level 5

Combination Therapy Considerations

• When using both medications together, follow the individual titration schedules for each medication 6, 7
• The combination of semaglutide and empagliflozin has shown complementary effects on glycemic control and weight reduction 4, 6
• Semaglutide has demonstrated superior HbA1c reduction compared to SGLT2 inhibitors, with an estimated treatment difference of -0.49 percentage points 4
• When initiating combination therapy, monitor closely for potential additive effects on volume status and blood pressure 6, 7

Common Pitfalls to Avoid

• Failing to follow the gradual titration schedule for semaglutide can lead to increased gastrointestinal side effects and potential discontinuation 4, 5
• Initiating empagliflozin in patients with severe renal impairment (eGFR <20 mL/min/1.73 m²) is not recommended 1, 2
• Not adjusting concomitant diabetes medications (especially insulin or sulfonylureas) when starting either medication increases hypoglycemia risk 2
• Forgetting to discontinue empagliflozin before surgical procedures increases ketoacidosis risk 1, 2