Combining Januvia (Sitagliptin) with Trulicity (Dulaglutide)
Yes, Januvia (sitagliptin) can be used with Trulicity (dulaglutide), but this combination is not recommended because it provides no additional clinical benefit and increases cost and pill burden without improving outcomes.
Why This Combination Should Be Avoided
Mechanism of Action Overlap
- Both medications work through the incretin pathway, making their combination redundant 1, 2.
- Sitagliptin is a DPP-4 inhibitor that prevents the breakdown of endogenous GLP-1, while dulaglutide is a GLP-1 receptor agonist that directly activates GLP-1 receptors 3, 4, 5.
- The ADA explicitly recommends discontinuing DPP-4 inhibitors before starting GLP-1 receptor agonists because the GLP-1 agonist provides superior glycemic control and cardiovascular benefits 1.
Clinical Evidence Against Combination
- In head-to-head trials, dulaglutide demonstrated superior efficacy to sitagliptin when added to metformin, with greater HbA1c reductions 2.
- Dulaglutide provides proven cardiovascular benefits with a hazard ratio of 0.88 for MACE reduction, benefits not demonstrated with sitagliptin 6, 7.
- No clinical trials support adding sitagliptin to dulaglutide therapy, and the incretin effect is already maximally stimulated by the GLP-1 receptor agonist 2, 5.
The Correct Approach: Choose Trulicity Over Januvia
When to Prioritize Trulicity
- For patients with established atherosclerotic cardiovascular disease, GLP-1 receptor agonists like dulaglutide are preferred over DPP-4 inhibitors due to proven MACE reduction 6, 8.
- For patients with chronic kidney disease (eGFR <60 mL/min/1.73m² or albuminuria ≥30 mg/g), dulaglutide requires no dose adjustment and provides kidney protection, while sitagliptin requires dose reduction 6.
- For patients needing weight loss, dulaglutide (especially 1.5 mg weekly) consistently reduces body weight, while sitagliptin is weight-neutral 2, 5.
Dosing Adjustments When Switching
- Discontinue sitagliptin when initiating dulaglutide 1.
- Start dulaglutide at 0.75 mg subcutaneously once weekly, with option to increase to 1.5 mg weekly for additional glycemic control 5.
- If the patient is on a sulfonylurea or insulin, reduce sulfonylurea dose by 50% or basal insulin by 20% when starting dulaglutide to prevent hypoglycemia 1.
Renal Dosing Considerations
Sitagliptin Limitations
- Requires dose reduction to 50 mg daily with eGFR 30-45 mL/min/1.73m² and to 25 mg daily with eGFR <30 mL/min/1.73m² 6.
Dulaglutide Advantages
- No dose adjustment required regardless of kidney function, making it simpler and more effective in CKD patients 6.
- Can be used in patients with eGFR as low as 2 mL/min/1.73m² 8.
Common Pitfalls to Avoid
Don't Continue Both Medications
- The most common error is continuing sitagliptin when adding dulaglutide "just to be safe" - this provides no benefit and increases costs 1, 2.
- The GLP-1 receptor agonist supersedes the DPP-4 inhibitor in the treatment algorithm 8, 1.
Monitor for GI Side Effects
- Dulaglutide causes nausea, vomiting, and diarrhea in a significant proportion of patients, similar to other GLP-1 agonists 2, 5.
- Start at the lowest dose (0.75 mg weekly) and titrate slowly to mitigate gastrointestinal symptoms 1.