Which medications should be discontinued or adjusted when titrating Mounjaro (tirzepatide)?

From the Guidelines

When titrating Mounjaro (tirzepatide), medications such as insulin, sulfonylureas, and meglitinides should be adjusted or discontinued to prevent hypoglycemia and other adverse effects.

Medications Requiring Adjustment or Discontinuation

• Insulin: doses should be reduced by 20-50% when initiating tirzepatide, with further adjustments based on blood glucose monitoring 1
• Sulfonylureas: may need dose reduction or discontinuation, especially when tirzepatide doses exceed 5 mg weekly 1
• Meglitinides: should be used cautiously with potential dose reductions 1
• SGLT2 inhibitors: can generally be continued but may require monitoring for dehydration and genital infections 1
• Medications that slow gastric emptying: should be evaluated as tirzepatide also delays gastric emptying, potentially affecting medication absorption 1
• Oral medications with narrow therapeutic indices: may require more frequent monitoring due to potential absorption changes 1

Rationale for Adjustments

The adjustments are necessary because tirzepatide, a dual GIP and GLP-1 receptor agonist, enhances insulin secretion and slows gastric emptying, which can potentiate hypoglycemia risk when combined with other glucose-lowering medications and alter the pharmacokinetics of certain drugs 1.

Key Considerations

• Monitor blood glucose levels closely when adjusting medications during tirzepatide titration 1
• Be aware of the potential for dehydration and genital infections when continuing SGLT2 inhibitors with tirzepatide 1
• Evaluate the need for dose adjustments of medications that slow gastric emptying, such as opioids and anticholinergics, when used with tirzepatide 1

From the FDA Drug Label

When initiating MOUNJARO, consider reducing the dose of concomitantly administered insulin secretagogues (e.g., sulfonylureas) or insulin to reduce the risk of hypoglycemia [see Warnings and Precautions (5.3)]. MOUNJARO delays gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with MOUNJARO. Monitor patients on oral medications dependent on threshold concentrations for efficacy and those with a narrow therapeutic index (e.g., warfarin) when concomitantly administered with MOUNJARO. Advise patients using oral hormonal contraceptives to switch to a non-oral contraceptive method, or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation with MOUNJARO.

The medications that should be discontinued or adjusted while Mounjaro is being titrated are:

• Insulin secretagogues (e.g., sulfonylureas): consider reducing the dose to reduce the risk of hypoglycemia
• Insulin: consider reducing the dose to reduce the risk of hypoglycemia
• Oral medications with a narrow therapeutic index (e.g., warfarin): monitor patients when concomitantly administered with MOUNJARO
• Oral hormonal contraceptives: advise patients to switch to a non-oral contraceptive method, or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation with MOUNJARO 2

From the Research

Medications to be Discontinued or Adjusted

When titrating Mounjaro (tirzepatide), the following medications should be discontinued or adjusted:

• Insulin: The dosage of insulin may need to be adjusted when initiating or titrating Mounjaro, as the combination of these medications can increase the risk of hypoglycemia 3
• Sulfonylureas: Medications such as glipizide may need to be discontinued or adjusted due to the increased risk of hypoglycemia when used in combination with Mounjaro 4
• Other glucose-lowering medications: The dosage of other glucose-lowering medications, such as metformin, may need to be adjusted when initiating or titrating Mounjaro, as the combination of these medications can increase the risk of hypoglycemia or other adverse effects 5, 6, 7

Considerations for Medication Adjustment

When adjusting medications during Mounjaro titration, the following considerations should be taken into account:

• Glycemic control: The patient's glycemic control should be closely monitored, and adjustments made to minimize the risk of hypoglycemia or hyperglycemia 3
• Adverse effects: The patient should be monitored for adverse effects, such as nausea, diarrhea, and vomiting, and adjustments made to minimize these effects 5, 3
• Renal function: The patient's renal function should be closely monitored, as Mounjaro may affect renal function, particularly when used in combination with other medications 7