Do you stop Trajenta (Linagliptin) when starting a patient on Ozempic (Semaglutide)?

Should You Stop Trajenta (Linagliptin) When Starting Ozempic (Semaglutide)?

Yes, you should stop Trajenta (linagliptin) when starting Ozempic (semaglutide) because GLP-1 receptor agonists and DPP-4 inhibitors should not be prescribed in combination. 1

Why These Medications Should Not Be Combined

DPP-4 inhibitors (like Trajenta) and GLP-1 receptor agonists (like Ozempic) work through overlapping mechanisms and should not be used together. 1 Here's the reasoning:

• DPP-4 inhibitors work by preventing the breakdown of endogenous GLP-1, thereby increasing its levels in the body 2
• GLP-1 receptor agonists directly activate GLP-1 receptors with pharmacologic doses of GLP-1 analogs 1
• Combining these agents provides no additional glycemic benefit and only increases medication burden and cost 1

Clinical Approach When Transitioning

When adding Ozempic to a patient currently on Trajenta, follow this approach:

Step 1: Assess Current Glycemic Control

• If the patient is meeting glycemic targets on Trajenta, you can safely discontinue it when adding Ozempic, as the GLP-1 receptor agonist will provide superior glucose-lowering efficacy 1
• If not meeting targets, discontinuing Trajenta while adding Ozempic will likely improve control, as GLP-1 receptor agonists are more potent than DPP-4 inhibitors 2

Step 2: Discontinue Trajenta

• Stop linagliptin completely when initiating semaglutide 1
• No tapering is required for DPP-4 inhibitors 2

Step 3: Initiate Ozempic with Proper Titration

• Start semaglutide at 0.25 mg once weekly and titrate gradually to minimize gastrointestinal side effects 3
• Continue metformin if the patient is on it, as metformin should be continued when adding other agents 1

Step 4: Adjust Other Medications if Needed

• If the patient is on insulin or sulfonylureas, consider dose reduction to prevent hypoglycemia when adding Ozempic 1, 3
• For patients on insulin or sulfonylureas currently meeting glycemic targets, it may be necessary to reduce doses of these medications (not metformin) to facilitate safe addition of the GLP-1 receptor agonist 1

Important Caveats

Hypoglycemia Risk

• DPP-4 inhibitors have minimal hypoglycemia risk when used alone, but this increases when combined with insulin secretagogues 2, 4
• GLP-1 receptor agonists also have low hypoglycemia risk alone, but risk increases when combined with insulin or sulfonylureas 1, 3

Renal Considerations

• Linagliptin requires no dose adjustment in renal impairment (a unique advantage among DPP-4 inhibitors) 2, 5, 4
• Semaglutide also requires no dose adjustment in renal impairment, including end-stage renal disease 3

Why Choose Ozempic Over Trajenta

The decision to add Ozempic likely reflects prioritizing:

• Superior cardiovascular benefits with GLP-1 receptor agonists compared to DPP-4 inhibitors 1, 2
• Greater weight loss with GLP-1 receptor agonists versus weight-neutral DPP-4 inhibitors 2, 6
• More potent glucose-lowering (HbA1c reduction of 1.0-1.5% with GLP-1 RAs vs 0.4-0.9% with DPP-4 inhibitors) 2

Common Pitfall to Avoid

Do not continue both medications thinking you'll get additive benefit. The KDIGO 2020 guidelines explicitly state that GLP-1 receptor agonists should not be used in combination with DPP-4 inhibitors 1. This combination wastes resources and exposes patients to unnecessary medication burden without clinical benefit.