What additional medication can be added to Tresiba (insulin degludec) for a patient with an elevated Hemoglobin A1C (HbA1C) level?

Adding Medication to Tresiba for A1C of 10%

For a patient on Tresiba (insulin degludec) with an A1C of 10%, add a GLP-1 receptor agonist (preferably liraglutide 1.8 mg daily) as the first-line additional agent, or add metformin if not already prescribed. 1

Immediate Treatment Intensification Required

With an A1C of 10%, this represents severe hyperglycemia requiring urgent treatment intensification. 1, 2

First Priority: Add GLP-1 Receptor Agonist

If the patient is not already on a GLP-1 RA, this is your primary add-on therapy. 1

• Liraglutide is the preferred GLP-1 RA based on the most convincing cardiovascular benefit data, titrated to 1.8 mg daily for optimal effect 1
• GLP-1 RAs provide significant A1C reduction (approximately 1.0-1.5% reduction) when added to basal insulin 1
• These agents offer weight loss rather than weight gain, a critical advantage over intensifying insulin alone 3
• Start at the lowest dose and up-titrate slowly to the maximal tolerated dose to minimize gastrointestinal side effects 1
• Fixed-ratio combination products (basal insulin + GLP-1 RA) are available and appropriate if formulary allows 1

Second Priority: Ensure Metformin is Maximized

If not already prescribed, add metformin as it should be the foundation of therapy. 3

• Metformin combined with insulin reduces insulin requirements by approximately 17% and improves A1C by an additional 0.74% 4
• Start metformin at 500-1000 mg daily and titrate to 2000 mg daily (1000 mg twice daily) for maximal effect 3, 5
• Metformin also reduces total cholesterol and improves the overall cardiovascular risk profile 4

Third Priority: Consider SGLT2 Inhibitor

If cardiovascular disease or heart failure is present, add an SGLT2 inhibitor (empagliflozin 10 mg daily preferred). 1

• Empagliflozin is the preferred SGLT2 inhibitor based on cardiovascular outcome data 1
• No dose titration needed for cardiovascular benefit; start at 10 mg daily 1
• SGLT2 inhibitors reduce both major adverse cardiovascular events and heart failure risk 1
• These agents provide additional A1C reduction of 0.5-0.7% when added to insulin 6
• Monitor for genital mycotic infections and educate about euglycemic diabetic ketoacidosis risk 1

Optimize Basal Insulin Dosing

Before adding prandial insulin, ensure Tresiba is adequately dosed. 1, 3

• Assess current Tresiba dose; maximum should not exceed approximately 0.5 units/kg/day to avoid overbasalization 3
• If fasting blood glucose remains elevated despite adequate basal insulin, increase Tresiba by 2 units every 3 days until fasting glucose reaches target (<130 mg/dL) 1, 2
• Check for clinical signals of overbasalization: elevated bedtime-to-morning glucose differential, hypoglycemia, or high glucose variability 1

When to Add Prandial Insulin

Only add prandial insulin if A1C remains above goal after optimizing basal insulin and adding GLP-1 RA. 1

• Start with one dose of rapid-acting insulin (aspart, lispro, or glulisine) with the largest meal 1
• Initial dose: 4 units or 10% of basal insulin dose 1, 3
• Titrate by increasing 1-2 units or 10-15% twice weekly based on postprandial glucose readings 1, 3
• If A1C <8% when adding prandial insulin, consider lowering basal dose by 4 units or 10% to prevent hypoglycemia 1

Critical Monitoring and Safety

Reassess treatment every 3-6 months to avoid therapeutic inertia. 1

• For any hypoglycemia: determine cause and reduce corresponding insulin dose by 10-20% 1, 3
• Prescribe glucagon for emergent hypoglycemia when intensifying insulin therapy 1
• Provide comprehensive education on self-monitoring of blood glucose, hypoglycemia recognition and treatment, and medication administration 1

Cost and Patient Preference Discussion

Before initiating GLP-1 RA or SGLT2 inhibitor, discuss out-of-pocket costs as these are expensive medications. 1

• Review potential side effects, drug-drug interactions, and safety issues clearly 1
• Elicit patient preferences and concerns about injectable versus oral medications 1
• Consider generic options when available to reduce cost burden 1