What is the recommended initial dose of Glyxambi (empagliflozin and linagliptin) for a patient at the clinic?

Initial Dosing of Glyxambi (Empagliflozin/Linagliptin)

For patients starting Glyxambi therapy, the recommended initial dose is 10 mg empagliflozin/5 mg linagliptin taken once daily, which is the lowest available dose. 1

Rationale for Starting at Lowest Dose

Starting at the lowest dose of Glyxambi is supported by several key considerations:

1. Cardiovascular Risk Reduction: The American College of Cardiology recommends initiating SGLT2 inhibitors with demonstrated cardiovascular benefit at the lowest available dose. There is no evidence of a graded dose response regarding cardiovascular outcomes, so the lowest dose (10 mg for empagliflozin) provides optimal cardiovascular protection. 2

2. Safety Profile: Starting at the lowest dose minimizes potential side effects while still providing clinical benefits. The combination therapy has been shown to be well-tolerated with a safety profile similar to the individual components. 3, 4

3. Glycemic Efficacy: Even at the lowest dose, the combination of empagliflozin 10 mg/linagliptin 5 mg provides significant HbA1c reduction (-1.08%) compared to either component alone. 3

4. Renal Considerations: For patients with renal impairment, lower doses are particularly important. Empagliflozin is not recommended for glycemic control in patients with eGFR <45 mL/min/1.73 m², making the lower dose more appropriate for patients with borderline renal function. 2

Dosing Algorithm

• Initial dose: Empagliflozin 10 mg/Linagliptin 5 mg once daily
• Timing: Take in the morning with or without food
• Dose adjustment: No dose titration is needed for cardiovascular risk reduction
• Alternative dosing: Higher dose (Empagliflozin 25 mg/Linagliptin 5 mg) may be considered only if additional glycemic control is needed after 12 weeks

Monitoring After Initiation

• Assess renal function within first few weeks of therapy
• Monitor for genital mycotic infections, particularly in women
• Watch for signs of volume depletion, especially if patient is on diuretics
• Monitor for rare but serious side effects such as diabetic ketoacidosis

Special Considerations

• Renal Function: For patients with eGFR 30-59 mL/min/1.73 m², maintain at lowest dose (10 mg empagliflozin component) 2
• Cardiovascular Disease: The 10 mg dose of empagliflozin is sufficient for cardiovascular protection 2
• Combination with Other Medications: If patient is on sulfonylureas or insulin, consider reducing their doses by approximately 20% when starting Glyxambi to prevent hypoglycemia 2

Clinical Evidence

Multiple clinical trials support starting with the lowest dose combination:

• In a 52-week study, empagliflozin 10 mg/linagliptin 5 mg provided substantial HbA1c reduction (-1.08%) with 57.8% of patients achieving HbA1c <7% at 24 weeks 3
• A meta-analysis of 6 randomized controlled trials showed that the 10 mg/5 mg combination led to significantly greater reductions in HbA1c compared to either drug alone, with a similar safety profile 4
• The fixed-dose combination reduces regimen complexity and may enhance medication adherence 5

Potential Pitfalls to Avoid

• Avoid starting at higher doses unless specifically indicated for glycemic control, as cardiovascular benefits are achieved at the lowest dose
• Do not initiate in patients with eGFR <30 mL/min/1.73 m² 2
• Discontinue at least 3 days before planned surgery to prevent postoperative ketoacidosis 2
• Use caution in patients with prior history of genital mycotic infections

By starting with the lowest available dose of Glyxambi (10 mg empagliflozin/5 mg linagliptin), you optimize the benefit-risk profile while still achieving significant glycemic control and cardiovascular protection for your patients.