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Polypharmacy with GLP1-RA and DPP-4 Inhibitors

PSA for people with Type 2 Diabetes on both glucagon-like peptide-1 receptor agonists (GLP1-RA) and a dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitors)


I often see new patients in my clinic who are taking both. This is not only ineffective, but it is also expensive. Both types of medication target the incretin system. Endogenous (internally produced) incretin works to stimulate glucose-dependent insulin production, suppress appetite, and inhibit glucose secretion. This hormone response is blunted in people with type 2 diabetes, therefore both drug classes can be valuable treatment options for someone with type 2 diabetes.


The drug class GLP1-RA’s act as incretin mimetics while DPP-4 inhibitors inhibit the breakdown of incretin.


Based on their mechanism of action, you would think that it may be helpful to take them together. However, this is not the case. Though endogenous DPP-4 inhibits the breakdown of endogenous incretin, it cannot break down GLP1-RA/incretin mimetics. Taking a DPP4-inhibitor with a GLP1-RA is therefore ineffective.


Other reasons to avoid taking these classes together:

  • Polypharmacy or treating a patient with multiple medications for the same condition. Though in type 2 diabetes, this is often necessary, it increases patient burden and non-adherence.

  • Cost: both these drug classes are expensive and not available in generic form.

  • Combination is not approved by FDA nor recommended by ADA

  • Increased risk for side effects: both medication have similar adverse event profiles


If you are taking both a GLP1-RA and DPP-4 inhibitor, please bring this up to your clinician. GLP1-RAs are often the preferred drug class due to their superior A1c reduction, weight reduction, and cardiovascular benefits, but it is, of course, patient dependent!


Available GLP1-RA:

  • Liraglutide (Victoza)

  • Dulaglutide (Trulicity)

  • Exenatide (Byetta, Bydureon, Bcise)

  • Semaglutide (Ozempic, Rybelsus)


Available DPP-4 inhibitors:

  • Sitagliptin (Januvia)

  • Linagliptin (Tradjenta)

  • Alogliptin (Nesina)

  • Saxagliptin (Onglyza)



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