How long should DPP-4 inhibitors be discontinued before starting GLP-1 analogues?

Discontinuation of DPP-4 Inhibitors Before Starting GLP-1 Analogues

DPP-4 inhibitors should be discontinued at least three half-lives before starting GLP-1 receptor agonists, which typically means stopping the DPP-4 inhibitor on the same day you start the GLP-1 analogue. 1

Rationale for Discontinuation

DPP-4 inhibitors and GLP-1 receptor agonists work through related but different mechanisms in the incretin pathway:

• DPP-4 inhibitors block the breakdown of endogenous GLP-1, increasing levels of active GLP-1 hormone
• GLP-1 receptor agonists directly activate GLP-1 receptors at pharmacological levels

There is no clinical benefit to using both medications simultaneously because:

1. The mechanisms overlap - both ultimately increase GLP-1 receptor activation
2. GLP-1 receptor agonists provide superior glycemic control and weight loss compared to DPP-4 inhibitors 2
3. Using both medications increases cost without providing additional benefit

Practical Recommendations

Timing of Discontinuation

• Stop the DPP-4 inhibitor when initiating the GLP-1 receptor agonist
• No washout period is required between stopping DPP-4 inhibitors and starting GLP-1 analogues
• The American Diabetes Association guidelines do not specify a required washout period between these medication classes 3

Medication-Specific Considerations

• For patients transitioning from DPP-4 inhibitors to GLP-1 receptor agonists, expect improved glycemic control and weight loss following the switch 2
• When starting GLP-1 receptor agonists, follow standard dose titration protocols to minimize gastrointestinal side effects:
  • Start with the lowest dose
  • Titrate up gradually according to product-specific guidelines
  • Monitor for nausea, vomiting, and diarrhea

Special Considerations

Perioperative Management

If a patient is scheduled for surgery after starting a GLP-1 receptor agonist:

• GLP-1 receptor agonists should be stopped for at least three half-lives before surgery to minimize aspiration risk 1
• For long-acting GLP-1 RAs (e.g., semaglutide): stop 3 weeks before surgery
• For short-acting GLP-1 RAs (e.g., liraglutide): stop 3-5 days before surgery

Monitoring After Transition

• Monitor glycemic control closely after transitioning from DPP-4 inhibitor to GLP-1 receptor agonist
• Expect improved glycemic control and potential weight loss with GLP-1 receptor agonists
• Be vigilant for gastrointestinal side effects, which are more common with GLP-1 receptor agonists than with DPP-4 inhibitors

Pitfalls to Avoid

• Do not continue DPP-4 inhibitors alongside GLP-1 receptor agonists as this provides no additional benefit and increases medication costs
• Do not expect immediate maximal efficacy from GLP-1 receptor agonists - full effect may take several weeks as dose is titrated
• Do not overlook the need for proper patient education regarding injection technique and management of potential gastrointestinal side effects when transitioning to injectable GLP-1 analogues

In summary, when transitioning from a DPP-4 inhibitor to a GLP-1 receptor agonist, simply discontinue the DPP-4 inhibitor when starting the GLP-1 analogue, with no required washout period between the two medication classes.