What to do if a patient's Hemoglobin A1c (HbA1c) levels drop while taking 2.5 mg of Mounjaro (tirzepatide)?

Expected A1C Reduction with Mounjaro 2.5 mg

The 2.5 mg dose of Mounjaro (tirzepatide) is intended solely for treatment initiation and is not designed to achieve glycemic control—you should not expect meaningful A1C reduction at this dose. 1

Dosing Strategy and A1C Expectations

Initial Dosing Phase

• Mounjaro must be started at 2.5 mg once weekly for the first 4 weeks to minimize gastrointestinal adverse reactions (nausea, diarrhea, vomiting), not for glucose lowering 1
• After this 4-week initiation period, the dose should be increased to 5 mg once weekly, which is the first therapeutic dose 1

Expected A1C Reductions by Dose

Based on the FDA label and clinical trial data, the following A1C reductions can be anticipated when tirzepatide is added to existing therapy:

• 5 mg dose: Approximately 2.1% reduction in A1C from baseline 1, 2
• 10 mg dose: Approximately 2.3-2.4% reduction in A1C from baseline 1, 2
• 15 mg dose: Approximately 2.3-2.4% reduction in A1C from baseline 1, 2

Dose Escalation Algorithm

• Start at 2.5 mg weekly for 4 weeks (initiation only) 1
• Increase to 5 mg weekly after 4 weeks 1
• If additional glycemic control is needed after at least 4 weeks on current dose, increase in 2.5 mg increments 1
• Maximum dose is 15 mg once weekly 1

Clinical Context and Comparisons

Superiority Over Other Agents

When added to basal insulin (insulin glargine) with or without metformin:

• Tirzepatide 10 mg achieved 83% of patients reaching A1C <7% compared to 49% with insulin glargine alone 1
• Tirzepatide 15 mg achieved 85% of patients reaching A1C <7% compared to 49% with insulin glargine alone 1
• When added to insulin glargine, tirzepatide 10-15 mg reduced A1C by 1.5% more than placebo at 40 weeks 2

Weight Loss Benefits

Unlike most diabetes medications, tirzepatide produces substantial weight loss:

• 5 mg dose: Mean weight loss of 6.4 kg 1
• 10 mg dose: Mean weight loss of 8.9 kg 1
• 15 mg dose: Mean weight loss of 10.6 kg 1

Important Clinical Considerations

Gastrointestinal Adverse Events

• The 2.5 mg starting dose is specifically designed to reduce GI side effects that occur in 11-26% of patients (nausea, diarrhea, vomiting) 1, 2
• These symptoms are typically mild to moderate and improve with continued use 2

Hypoglycemia Risk

• Tirzepatide has very low hypoglycemia risk when used alone or with metformin 2
• When combined with insulin, hypoglycemia rates are significantly lower than with prandial insulin (0.4 vs 4.4 events per patient-year) 3
• If patient is on sulfonylureas, consider dose reduction when initiating tirzepatide to minimize hypoglycemia risk 4

Discontinuation Effects

• If tirzepatide is discontinued, A1C re-elevation and weight regain occur relatively early (within 2-4 months), suggesting need for continuous therapy 5
• This emphasizes that the 2.5 mg dose should only be used for the initial 4-week period before escalation 5

Racial Differences

• Asian patients may experience more gastrointestinal adverse events but greater weight loss compared to non-Asian patients 6
• Non-Asian patients may achieve better glycemic control at the same doses 6