Answer:

The 2019 ADA Standards of Care (Fig 9.1) and the ADA/EASD Consensus report (Fig 8) recommend that when you initiate the GLP1RA, you should stop the DPP4I.  There is no benefit to using both drugs together.

Background:

The newer standards of care recommend that providers consider using GLP1RAs or SGLT2Is in patients with Established ASCVD, based on positive effects from the cardiovascular outcome trials in patients with established ASCVD (with specific agents).  These two classes are also recommended for patients with CKD and/or Heart Failure (with a preference for SGTL2I).  GLP1RAs and SGLT2Is are also preferred for patients that need to minimize weight gain, promote weight loss with a low risk of hypoglycemia.  For these reasons, many patients would benefit from taking a GLP1RA instead of a DPP4I.  Although DPP4I are oral, once daily, with high tolerability, they have no evidence of reduction in CVD events and are less efficacious overall.  However, the patient must be willing to change to injectable therapy.

Rationale:

Both drugs work in the incretin system.  The mechanism of action of DPP4I is to prevent the breakdown of endogenous GLP1.  Studies have shown that DPP4I do not extend the duration or change the amount of exogenously injected GLP1RA.  Also, many patients with Type 2 diabetes lack sufficient endogenous GLP1 production, which accounts for the limited efficacy of the DPP4I class.    Therefore, there is no evidence to support combination therapy.  Stopping the DPP4i will decrease pill burden, costs, and potential for additive risks (both classes have a warning for pancreatitis).

1.     Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) [published online October 5, 2018]. Diabetes Care. doi:10.2337/dci18-0033

2.     ADA.  Standards of Medical Care in Diabetes – 2019. Diabetes Care 2019 Jan; 42(supp1): S1-193. http://care.diabetesjournals.org/content/42/Supplement_1

3.     Bahathiq AO. Treatment of type 2 diabetes, GLP-1 Agonist and a DPP-4 Inhibitor. Journal of Proteomics Enzymology. 2018;7(1). https://www.scitechnol.com/peer-review/treatment-of-type-2-diabetes-glp1-agonist-and-a-dpp4-inhibitor-YBRX.php?article_id=7243. Published March 2, 2018. Accessed January 29, 2019.

4.     Nauck MA, Kahle M, Baranov O, et al. Addition of a dipeptidyl peptidase-4 inhibitor, sitagliptin, to ongoing therapy with the glucagon-like peptide-1 receptor agonist liraglutide: A randomized controlled trial in patients with type 2 diabetes. Diabetes Obes Metab 2017;19(2): 200-207.