Can you take Mounjaro (tirzepatide) and Januvia (sitagliptin) together?

Tirzepatide and Sitagliptin Should Not Be Used Together

You should not take Mounjaro (tirzepatide) and Januvia (sitagliptin) together as they have overlapping mechanisms of action and combining them is not recommended in clinical guidelines. 1

Why These Medications Cannot Be Combined

1. Mechanism of Action Conflict:

   • Tirzepatide (Mounjaro) is a dual GIP/GLP-1 receptor agonist 2
   • Sitagliptin (Januvia) is a DPP-4 inhibitor that increases endogenous GLP-1 levels 3
   • Both medications ultimately work through the incretin pathway, making their combination redundant and not supported by evidence

2. Guideline Recommendations:

   • Current diabetes management guidelines specifically advise against combining agents from the incretin classes (GIP/GLP-1 RAs, GLP-1 RAs, and DPP-4 inhibitors) with each other 1
   • The 2024 DCRM guidelines state: "do not combine agents from the incretin classes (GIP/GLP-1 RAs, GLP-1 RAs, and dipeptidyl peptidase 4 [DPP4] inhibitors) with each other" 1

Appropriate Medication Combinations with Tirzepatide

If you're currently taking tirzepatide (Mounjaro), these medications can be appropriately combined with it:

• Metformin: First-line therapy that works well with tirzepatide 1
• SGLT2 inhibitors: Can be combined with tirzepatide for additional benefits in patients with heart failure or chronic kidney disease 1, 4
• Insulin: Can be used with tirzepatide in some cases, though dose adjustments may be needed due to increased hypoglycemia risk 4

Appropriate Medication Combinations with Sitagliptin

If you're currently taking sitagliptin (Januvia), these medications can be appropriately combined with it:

• Metformin: Standard combination therapy 3
• Thiazolidinediones: Can be combined with sitagliptin 3
• SGLT2 inhibitors: Can provide complementary benefits 1
• Insulin: May be used together with appropriate dose adjustments 1

Clinical Considerations

Efficacy

• Tirzepatide is significantly more potent for both glucose control and weight loss than DPP-4 inhibitors like sitagliptin 5
• In clinical trials, tirzepatide demonstrated superior A1C reduction compared to GLP-1 receptor agonists like semaglutide, with reductions of up to 2.30 percentage points 5

Safety

• Both medications individually have low risks of hypoglycemia when used without insulin 4, 3
• Combining them would not provide additional benefits but could increase the risk of adverse effects
• Tirzepatide's most common side effects are gastrointestinal (nausea, diarrhea, decreased appetite) 2, 5

What To Do If You're Currently Taking Both

If you are currently taking both medications:

1. Do not stop either medication abruptly
2. Consult your healthcare provider immediately to adjust your medication regimen
3. Your provider will likely recommend discontinuing one of the medications, typically the sitagliptin, as tirzepatide is more potent for glucose control and weight management 5

Alternative Approaches

For patients with type 2 diabetes requiring multiple medications:

• Tirzepatide + metformin + SGLT2 inhibitor: Powerful combination for patients with cardiovascular or kidney disease 1
• Sitagliptin + metformin + SGLT2 inhibitor: Alternative combination if tirzepatide is not tolerated 1
• Basal insulin + either medication: Can be considered for patients with significantly elevated blood glucose 1

Remember that medication choices should be guided by your specific health conditions, A1C levels, and treatment goals. Always consult with your healthcare provider before making any changes to your diabetes medication regimen.