Can a patient take Januvia (Sitagliptin) with Mounjaro (Tirzepatide)?

Can a Patient Take Januvia with Mounjaro?

No, combining Januvia (sitagliptin) with Mounjaro (tirzepatide) is not recommended because these medications have overlapping mechanisms of action that provide minimal additional glycemic benefit, and guidelines specifically advise against combining DPP-4 inhibitors with GLP-1 receptor agonists. 1

Why This Combination Should Be Avoided

Overlapping Mechanisms of Action

• Januvia (sitagliptin) is a DPP-4 inhibitor that increases insulin secretion and reduces glucagon secretion in a glucose-dependent manner 2
• Mounjaro (tirzepatide) is a dual GIP/GLP-1 receptor agonist that works through similar pathways—stimulating insulin secretion and reducing glucagon secretion in a glucose-dependent manner 3, 4
• The American Diabetes Association explicitly recommends selecting the most effective single agent rather than combining medications with overlapping mechanisms, as adding a DPP-4 inhibitor like sitagliptin to a GLP-1 receptor agonist provides minimal additional glycemic benefit 1

Superior Efficacy of Tirzepatide Alone

• Tirzepatide demonstrates substantially greater glucose-lowering efficacy than DPP-4 inhibitors, with HbA1c reductions of 1.87% to 2.59% compared to the 0.4% to 0.9% reduction seen with DPP-4 inhibitors 5, 2
• In the SURPASS-2 trial, tirzepatide achieved greater glycemic control and weight loss than semaglutide 1 mg, which itself is more potent than any DPP-4 inhibitor 3, 5
• Adding sitagliptin to tirzepatide would not meaningfully improve outcomes and only increases medication burden, cost, and potential side effects 1

Clinical Decision-Making Algorithm

If the Patient Is Currently on Both Medications:

Step 1: Assess Current Glycemic Control

• Check the most recent HbA1c level 1
• If HbA1c is at target (typically <7% for most patients), discontinue the sitagliptin and continue tirzepatide alone 1

Step 2: If HbA1c Is Above Target

• First, optimize the tirzepatide dose before considering any additional agents 1
• Tirzepatide is available in 5 mg, 10 mg, and 15 mg doses—ensure the patient is on an adequate dose 5
• Discontinue sitagliptin as it provides negligible additional benefit 1

Step 3: If Additional Glycemic Control Is Needed After Optimizing Tirzepatide

• Consider adding medications with complementary mechanisms of action 1:
  • Metformin (if not already on it)—first-line agent with proven cardiovascular benefits 2
  • SGLT2 inhibitors—provide cardiovascular and renal protection with complementary glucose-lowering effects 2
  • Basal insulin—if significant insulin deficiency is present 2

If Considering Starting This Combination:

Do not initiate both medications together. Instead:

• Start with tirzepatide alone, as it has superior efficacy for both glucose lowering and weight reduction 3, 4, 5
• Tirzepatide monotherapy achieved HbA1c reductions up to 2.59% and weight loss up to 12.9 kg in clinical trials 5
• Reserve combination therapy for agents with complementary mechanisms if tirzepatide alone is insufficient 1

Safety Considerations

Gastrointestinal Side Effects

• Both medications can cause gastrointestinal side effects (nausea, vomiting, diarrhea), and combining them may theoretically increase this risk 2, 3
• Tirzepatide's gastrointestinal side effects are dose-dependent and similar to GLP-1 receptor agonists 3, 4

Hypoglycemia Risk

• When used without insulin or sulfonylureas, both medications have minimal hypoglycemia risk 2, 5
• However, the combination provides no additional benefit to justify any potential increased risk 1

Special Population Considerations

Patients with Obesity

• Tirzepatide alone provides substantial weight loss benefits (16.5% to 22.4% body weight reduction in the SURMOUNT-1 trial), far exceeding what DPP-4 inhibitors offer (which are weight-neutral) 4, 2
• Adding sitagliptin would not enhance weight loss and is therefore not indicated 1

Patients with Cardiovascular Disease

• For patients with established cardiovascular disease, tirzepatide or other GLP-1 receptor agonists are preferred over DPP-4 inhibitors due to superior cardiovascular outcomes 1
• DPP-4 inhibitors have shown cardiovascular safety but no cardiovascular benefit in outcome trials 2
• The combination does not improve cardiovascular outcomes 1

Patients with Renal Impairment

• Tirzepatide can be used across the spectrum of renal function 2
• If a DPP-4 inhibitor were needed (which it is not in combination with tirzepatide), sitagliptin requires dose adjustment when eGFR <45 mL/min/1.73 m² 6

Common Pitfalls to Avoid

• Do not continue "legacy" medications without reassessing their necessity—if a patient was on sitagliptin before starting tirzepatide, the sitagliptin should be discontinued 1
• Do not assume "more is better"—combining medications with overlapping mechanisms increases cost and pill burden without meaningful clinical benefit 1
• Do not add sitagliptin if tirzepatide is not achieving target HbA1c—instead, optimize the tirzepatide dose or add an agent with a complementary mechanism 1

Bottom Line

Discontinue Januvia (sitagliptin) if the patient is taking Mounjaro (tirzepatide). The combination provides minimal additional benefit and is not supported by clinical guidelines. If additional glucose lowering is needed beyond optimized tirzepatide therapy, consider adding metformin, an SGLT2 inhibitor, or basal insulin—all of which have complementary mechanisms of action and proven benefits. 1, 2