What insulin dose adjustments are recommended for a 53-year-old female with type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, and diabetic neuropathy, currently on insulin glargine (long-acting insulin) 50 units subcutaneously twice daily and insulin aspart (rapid-acting insulin) 30 units subcutaneously three times daily, who is initiating tirzepatide (glucagon-like peptide-1 receptor agonist) and has a hemoglobin A1c (HbA1c) level of 12.5%?

Insulin Dose Adjustment When Initiating Tirzepatide

Reduce total daily insulin dose by approximately 20% immediately when starting tirzepatide to prevent hypoglycemia. 1, 2

Specific Dose Adjustments for This Patient

Basal Insulin (Insulin Glargine)

• Current dose: 50 units subcutaneously twice daily (100 units total daily)
• New dose: Reduce to 40 units twice daily (80 units total daily) 1, 2
• This represents a 20% reduction in total basal insulin 1, 2

Prandial Insulin (Insulin Aspart)

• Current dose: 30 units three times daily with meals (90 units total daily)
• New dose: Reduce to 24 units three times daily with meals (72 units total daily) 1, 2
• This represents a 20% reduction in total prandial insulin 1, 2

Discontinue Sitagliptin

• Stop sitagliptin (DPP-4 inhibitor) before starting tirzepatide 1
• GLP-1 receptor agonists and DPP-4 inhibitors should not be used together 1

Critical Monitoring Requirements

Immediate Monitoring (First 4 Weeks)

• Monitor blood glucose 4-7 times daily: fasting, pre-meal, and 2-hour post-meal readings 1, 2
• Check for hypoglycemia (glucose <70 mg/dL) requiring immediate additional dose reduction 1, 2
• If hypoglycemia occurs, reduce the corresponding insulin component by an additional 10-20% immediately 1, 2, 3

Ongoing Adjustments

• Expect further insulin reductions of 10-20% with each tirzepatide dose escalation (from 2.5 mg to 5 mg to 7.5 mg weekly) 2
• Reassess insulin requirements every 2-4 weeks during tirzepatide titration 2
• As glucose levels improve, continue reducing insulin rather than maintaining or increasing doses 2

Evidence Supporting This Approach

Guideline-Based Rationale

The American College of Cardiology explicitly recommends reducing total daily insulin dose by approximately 20% when initiating GLP-1 receptor agonists with demonstrated cardiovascular benefit to prevent hypoglycemia 1. This reduction should occur immediately with the first dose, not gradually 1, 2.

Clinical Trial Data

In the SURPASS-6 trial, tirzepatide added to basal insulin in patients with type 2 diabetes resulted in superior glycemic control compared to adding prandial insulin, with significantly lower hypoglycemia rates (0.4 vs 4.4 events per patient-year) 4. Real-world data from 62 patients with type 1 diabetes showed that tirzepatide reduced total daily insulin requirements from 81.9 units to 57.6 units (approximately 30% reduction) while improving time-in-range from 31% to 61% 5.

Foundation Therapy Considerations

Continue metformin unless contraindicated 1, 6, 2. Metformin remains the foundation of type 2 diabetes therapy even when using insulin and GLP-1 receptor agonists, as it reduces total insulin requirements and provides complementary glucose-lowering effects 1, 6.

Common Pitfalls to Avoid

Do Not Delay Insulin Reduction

The 20% insulin dose reduction must occur immediately with the first tirzepatide dose, not after observing glucose trends 1, 2. Delaying this reduction significantly increases hypoglycemia risk 1, 2.

Do Not Ignore Mild Hypoglycemia

Glucose levels of 54-70 mg/dL signal the need for additional insulin dose reduction, even if asymptomatic 2, 3. This patient has diabetic neuropathy, which may reduce symptomatic awareness of hypoglycemia 3.

Do Not Continue Escalating Insulin

If glucose levels improve with tirzepatide, reduce insulin further rather than maintaining current doses 2. The goal is to leverage tirzepatide's glucose-lowering effect while minimizing insulin requirements 4.

Anticipate Gastrointestinal Side Effects

Tirzepatide commonly causes nausea (14-26%), diarrhea (11-15%), and vomiting (5-13%) 4, 7. Start at the lowest dose (2.5 mg weekly) and uptitrate every 4 weeks as tolerated 1, 7. Recommend small portion sizes for meals to mitigate nausea 1.

Expected Outcomes

With appropriate insulin dose reduction and tirzepatide initiation, this patient can expect:

• HbA1c reduction of 2.0-2.5% from current 12.5% to approximately 10.0-10.5% within 12-16 weeks 4, 7
• Weight loss of 9-12 kg over 52 weeks 4, 7
• Reduced hypoglycemia risk compared to insulin intensification alone 4
• Further insulin dose reductions of 30-50% as tirzepatide is titrated to therapeutic doses 5

Sample Order

New Insulin Regimen (effective immediately upon tirzepatide initiation):

• Insulin glargine 40 units subcutaneously twice daily
• Insulin aspart 24 units subcutaneously three times daily with meals
• Discontinue sitagliptin 100 mg daily
• Continue current metformin dose (if on metformin)
• Tirzepatide 2.5 mg subcutaneously once weekly

Monitoring:

• Check blood glucose fasting, before each meal, and 2 hours after largest meal daily for first 4 weeks
• Contact provider if glucose <70 mg/dL for immediate insulin dose adjustment
• Follow-up in 2-4 weeks for insulin dose reassessment