What insulin regimen adjustment is recommended when increasing Trulicity (dulaglutide) from 0.75 mg to 1.5 mg in a patient on Lispro (insulin lispro) and Glargine (insulin glargine)?

Insulin Regimen Adjustment When Increasing Trulicity from 0.75 mg to 1.5 mg

When increasing Trulicity (dulaglutide) from 0.75 mg to 1.5 mg in a patient on Lispro 30 U with meals and Glargine 50 U twice daily, reduce the total daily insulin dose by 25-30%.

Rationale for Insulin Reduction

Dulaglutide is a once-weekly GLP-1 receptor agonist that improves glycemic control by enhancing glucose-dependent insulin secretion, reducing glucagon secretion, and slowing gastric emptying. When increasing the dose from 0.75 mg to 1.5 mg:

• The higher dose of dulaglutide provides greater glucose-lowering efficacy 1
• This increased efficacy necessitates a reduction in insulin dosage to prevent hypoglycemia
• Clinical evidence shows that dulaglutide 1.5 mg has superior glycemic control compared to the 0.75 mg dose 2

Specific Insulin Adjustment Recommendations

Basal Insulin (Glargine) Adjustment:

• Reduce glargine by 25-30% of current dose
• Current dose: 50 U AM + 50 U PM = 100 U total
• New dose: Approximately 35-40 U AM and 35-40 U PM (total 70-75 U)

Prandial Insulin (Lispro) Adjustment:

• Reduce lispro by 25-30% of current dose
• Current dose: 30 U with meals (90 U total)
• New dose: Approximately 20-22 U with meals (60-66 U total)

Implementation Strategy

1. First Week After Dose Increase:

   • Implement the insulin reduction immediately when increasing Trulicity to 1.5 mg
   • Monitor blood glucose more frequently (before meals and at bedtime)

2. Subsequent Adjustments:

   • Assess fasting glucose levels to guide further basal insulin adjustments
   • Target fasting glucose of 90-150 mg/dL 3
   • If 50% of fasting glucose readings are above target, increase glargine by 2 units
   • If more than 2 fasting readings per week are below 80 mg/dL, decrease glargine by 2 units

3. Prandial Insulin Titration:

   • Adjust lispro doses based on post-meal glucose patterns
   • Consider further reductions if post-meal hypoglycemia occurs

Monitoring and Safety Considerations

• Hypoglycemia Risk: The combination of dulaglutide with insulin significantly increases hypoglycemia risk compared to dulaglutide alone 4
• Glucose Monitoring: More frequent monitoring is essential during the first 2-4 weeks after dose adjustment
• Gastrointestinal Side Effects: Be aware that increasing dulaglutide dose may temporarily worsen nausea, vomiting, or diarrhea 4

Important Clinical Considerations

• Dulaglutide requires no dosage adjustments for renal impairment, making it advantageous over some other diabetes medications 1
• The AWARD-4 trial demonstrated that dulaglutide 1.5 mg with prandial insulin provided better glycemic control than basal-bolus insulin regimens 4
• If hypoglycemia persists despite insulin reduction, consider further decreasing insulin doses rather than reducing the dulaglutide dose
• Maintain metformin if the patient is currently taking it, as it works synergistically with dulaglutide and insulin 1

Common Pitfalls to Avoid

• Insufficient insulin reduction: Failing to reduce insulin enough when increasing dulaglutide can lead to hypoglycemia
• Overbasalization: Watch for signs of excessive basal insulin (high bedtime-to-morning glucose differential ≥50 mg/dL) 1
• Delayed adjustment: Don't wait for hypoglycemia to occur before reducing insulin doses
• Ignoring weight effects: Monitor for weight changes, as dulaglutide promotes weight loss while insulin can cause weight gain 1

By following this structured approach to insulin reduction when increasing Trulicity from 0.75 mg to 1.5 mg, you can optimize glycemic control while minimizing the risk of hypoglycemia.