How do you initiate Xultophy (insulin degludec/liraglutide) in a patient already on 50 units of degludec (insulin degludec)?

Initiating Xultophy in a Patient Already on 50 Units of Degludec

When transitioning from 50 units of insulin degludec to Xultophy (IDegLira), start Xultophy at 16 dose steps (16 units degludec/0.6 mg liraglutide) and discontinue the standalone degludec, then titrate upward based on fasting glucose targets. 1

Transition Strategy

The key principle is that Xultophy is not a unit-for-unit conversion from basal insulin alone. You must start at the recommended initial dose regardless of prior insulin dose:

• Discontinue the 50 units of degludec completely 1
• Start Xultophy at 16 dose steps once daily (equivalent to 16 units degludec + 0.6 mg liraglutide) 1
• This represents a significant reduction in basal insulin dose, but the addition of liraglutide provides complementary glucose-lowering through multiple mechanisms 2

Rationale for This Approach

The fixed-ratio combination provides synergistic effects that allow for lower insulin doses while achieving superior glycemic control:

• IDegLira achieves better A1C reduction than basal insulin alone at equivalent or lower insulin doses without increased hypoglycemia risk 2
• In clinical trials, patients on basal insulin who switched to IDegLira achieved A1C reductions of 1.9% versus 0.9% with insulin alone, despite using equivalent final insulin doses (around 45 units) 2
• The liraglutide component contributes distinct glucose-lowering effects beyond what insulin provides, justifying the lower starting insulin dose 2

Titration Protocol

After initiating at 16 dose steps, uptitrate progressively:

• Increase by 2 dose steps every 3-4 days based on fasting plasma glucose readings 1
• Target fasting glucose of 4-5 mmol/L (72-90 mg/dL) 2
• Maximum dose is 50 dose steps per day (50 units degludec + 1.8 mg liraglutide) 1
• The final insulin dose in IDegLira is typically similar to or lower than the previous basal insulin dose alone 2

Medication Adjustments

When initiating Xultophy, adjust other diabetes medications:

• Continue metformin 3
• Discontinue or reduce sulfonylureas to minimize hypoglycemia risk 3
• Discontinue DPP-4 inhibitors (contraindicated with GLP-1 agonists) 3
• Discontinue any standalone GLP-1 agonist if previously prescribed 3

Expected Clinical Outcomes

Patients transitioning to Xultophy can expect:

• Superior glycemic control: 49.4% of patients achieve A1C <7% without hypoglycemia or weight gain versus 7.2% with basal-bolus insulin 4
• Weight loss of approximately 2.7 kg rather than weight gain seen with insulin intensification 2
• Reduced hypoglycemia risk, particularly nocturnal hypoglycemia 4, 2
• Lower gastrointestinal side effects compared to full-dose liraglutide alone, though nausea may occur in approximately 6.5% of patients 2, 5

Critical Pitfalls to Avoid

Do not attempt unit-for-unit conversion from 50 units degludec to 50 dose steps of Xultophy initially—this would expose the patient to excessive liraglutide (1.8 mg) without proper titration, significantly increasing gastrointestinal side effects 1, 2

Do not continue standalone degludec alongside Xultophy—the combination product contains degludec, and dual therapy would cause insulin overdosing 1

Monitor closely during the first 2-4 weeks as the insulin dose is effectively reduced from 50 to 16 units initially; some patients may experience transient hyperglycemia requiring faster uptitration 2

Alternative Consideration

If the patient has previously failed GLP-1 agonist therapy due to gastrointestinal intolerance, Xultophy may still be appropriate since the liraglutide dose is lower and titrated gradually, resulting in better GI tolerability 6, 2. However, if severe GI intolerance occurred previously, consider alternative intensification strategies such as adding prandial insulin instead 3.