Can I use Januvia (Sitagliptin) with Ozempic (Semaglutide)?

Combining Januvia (Sitagliptin) with Ozempic (Semaglutide) is Not Recommended

You should not use Januvia (sitagliptin) together with Ozempic (semaglutide) as there is no added glucose-lowering benefit beyond using semaglutide alone, and this combination is specifically not recommended in clinical guidelines. 1

Mechanism of Action and Overlap

Both medications work through similar pathways:

• Ozempic (semaglutide) is a GLP-1 receptor agonist that directly stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner 1
• Januvia (sitagliptin) is a DPP-4 inhibitor that prevents the breakdown of natural GLP-1, indirectly increasing GLP-1 levels 1

Using both medications together is redundant since they both ultimately increase GLP-1 signaling.

Evidence Against Combination

The American Diabetes Association's 2025 Standards of Care explicitly states:

"We do not recommend using GLP-1 RAs (or the dual GIP and GLP-1 RA) together with a DPP-4 inhibitor as there is no added glucose-lowering benefit beyond that of the GLP-1 RA alone." 1

This recommendation is based on the understanding that:

1. GLP-1 RAs like semaglutide provide more potent glucose-lowering effects than DPP-4 inhibitors 1
2. The American College of Cardiology consensus statement also notes: "GLP-1RA should not be coadministered with DPP4 inhibitors given that they both work through GLP-1 signaling and have not been approved for use together." 1

Comparative Efficacy

Clinical trials have directly compared these medication classes:

• The PIONEER 3 trial showed that oral semaglutide 7mg and 14mg provided significantly greater HbA1c reductions than sitagliptin 100mg (-0.3% and -0.5% greater reductions, respectively) 2
• The SUSTAIN 2 trial demonstrated that once-weekly injectable semaglutide was superior to sitagliptin for both glycemic control and weight reduction 3

Alternative Approaches

If you're currently on Januvia and considering Ozempic:

• Switch to Ozempic: Replace Januvia with Ozempic for better glycemic control and additional benefits (weight loss, cardiovascular protection) 1
• Continue current therapy: If Januvia is working well and you prefer to avoid injectable medication

Special Considerations

• Renal function: Both medications can be used in reduced kidney function, though dose adjustments may be needed for sitagliptin when eGFR is <45 mL/min/1.73m² 1
• Cardiovascular disease: Semaglutide has demonstrated cardiovascular benefits, while sitagliptin has shown cardiovascular safety but no benefit 1
• Side effects: Semaglutide commonly causes gastrointestinal side effects (nausea, vomiting), while sitagliptin is generally better tolerated 1

Monitoring and Follow-up

If switching from Januvia to Ozempic:

• Start with the lowest dose of semaglutide (0.25mg weekly) and titrate slowly to minimize GI side effects 1
• Monitor for nausea, vomiting, and hypoglycemia, especially if also on insulin or sulfonylureas 1
• Be aware that semaglutide has been associated with diabetic retinopathy complications in some patients with pre-existing retinopathy 1

Remember that medication changes should always be done under medical supervision to ensure appropriate dosing and monitoring.