How to manage consistent hyperglycemia in a patient on Lispro (insulin lispro) and Tresiba (insulin degludec)?

Management of Persistent Hyperglycemia on Lispro and Tresiba

When hyperglycemia persists despite treatment with insulin lispro (rapid-acting) and Tresiba (insulin degludec, long-acting basal), you must systematically increase both basal and prandial insulin doses while ensuring proper timing and technique, rather than continuing inadequate doses of either component. 1

Immediate Assessment and Dose Adjustment Algorithm

Step 1: Verify Current Insulin Doses and Timing

Check if basal insulin (Tresiba) is adequate:

• If fasting glucose ≥180 mg/dL: Increase Tresiba by 4 units every 3 days 1
• If fasting glucose 140-179 mg/dL: Increase Tresiba by 2 units every 3 days 1
• Target fasting glucose: 80-130 mg/dL 1

Critical threshold to recognize: Once Tresiba exceeds 0.5 units/kg/day and approaches 1.0 units/kg/day without achieving glycemic control, the problem is likely insufficient prandial coverage rather than inadequate basal insulin 1, 2

Step 2: Optimize Prandial Insulin (Lispro) Coverage

For persistent hyperglycemia with blood glucose in the 200s mg/dL:

• This indicates BOTH inadequate basal coverage AND insufficient mealtime insulin 1
• Increase lispro dose by 1-2 units (or 10-15%) before each meal every 3 days based on pre-meal and 2-hour postprandial readings 1
• In hyperglycemic patients (glucose >180 mg/dL), administer lispro 15 minutes BEFORE meals rather than at mealtime to optimize postprandial control 3

Step 3: Rule Out Contributing Factors

Corticosteroid use:

• Steroids cause afternoon and evening hyperglycemia with peak effects 7-9 hours after dosing 2
• If on dexamethasone or prednisone: Add NPH insulin 0.3 units/kg/day (give 2/3 in morning, 1/3 in early evening) to existing regimen 2
• Insulin requirements decline rapidly when steroids are stopped 2

Medication interactions:

• Atypical antipsychotics, corticosteroids, diuretics, estrogens, thyroid hormones, and sympathomimetics all reduce insulin effectiveness 4
• Increase insulin doses and monitoring frequency when these drugs are co-administered 4

Step 4: Ensure Foundation Therapy

Verify metformin use (for Type 2 diabetes):

• Metformin should be continued unless contraindicated, even when intensifying insulin therapy 1, 2
• This remains the foundation of Type 2 diabetes management 1

Specific Dosing Recommendations

If Currently Insulin-Naive or on Low Doses:

• Start with total daily dose of 0.3-0.5 units/kg/day 5
• Split 50/50 between basal (Tresiba) and prandial (lispro) 5
• For a 70 kg patient: approximately 21-35 units total daily (10-17 units Tresiba, 3-6 units lispro before each of 3 meals) 1

If Already on Insulin but Poorly Controlled:

• Increase basal insulin by 10-15% (approximately 4-6 units) 1
• Add or increase prandial insulin: start with 4 units before the largest meal or 10% of current basal dose 1
• Titrate both components systematically every 3 days 1

Critical Pitfalls to Avoid

Overbasalization:

• Continuing to escalate Tresiba beyond 0.5-1.0 units/kg/day without addressing postprandial hyperglycemia leads to suboptimal control and increased hypoglycemia risk 1
• Clinical signals: basal dose >0.5 units/kg/day, bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia episodes, high glucose variability 1

Improper lispro timing:

• In hyperglycemic patients, administering lispro at mealtime rather than 15 minutes before results in worse postprandial control 3
• Lispro administered 15-30 minutes pre-meal significantly reduces postprandial glucose excursion compared to mealtime dosing 3

Inadequate monitoring:

• Daily fasting glucose monitoring is essential during titration 1
• Check pre-meal and 2-hour postprandial glucose to guide prandial insulin adjustments 1

When to Consider Alternative Strategies

If basal insulin approaches 0.5-1.0 units/kg/day with controlled fasting glucose but elevated HbA1c:

• Add or intensify prandial insulin rather than further increasing basal insulin 1, 2
• Consider adding GLP-1 receptor agonist to minimize weight gain and hypoglycemia risk 1

For severe hyperglycemia (HbA1c ≥10%, glucose ≥300-350 mg/dL):

• Consider immediate basal-bolus regimen with higher starting doses (0.4-0.6 units/kg/day total) 1
• More aggressive titration may be warranted 2

Monitoring Requirements

• Check fasting glucose daily during active titration 1
• Monitor pre-meal and 2-hour postprandial glucose to guide prandial adjustments 1
• Reassess every 3 days during active titration, every 3-6 months once stable 1
• If hypoglycemia occurs, reduce dose by 10-20% and determine the cause 1