Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Adding DPP-4 Inhibitors to Metformin Therapy

What are clinical outcomes on patients with T2D?

Publish date:: November 17, 2015

In patients with type 2 diabetes, adding dipeptidyl peptidase-4 (DPP-4) inhibitors to metformin therapy was associated with lower risks for all-cause death, major adverse cardiovascular events (MACEs), ischemic stroke, and hypoglycemia when compared with sulfonylureas, according to a study of patients with type 2 diabetes aged 20 years and older. A total of 10,089 propensity score-matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined and results included:

• DPP-4 inhibitors were associated with lower risks for all-cause death (HR, 0.63), MACEs (HR, 0.68), ischemic stroke (HR, 0.64), and hypoglycemia (HR, 0.43) compared with sulfonylureas as add-on therapy to metformin.

• DPP-4 inhibitors had no effect on risks for myocardial infarction and hospitalization for heart failure.

Citation: Ou SM, Shih CJ, Chao PW, et al. Effects on clinical outcomes of adding dipeptidyl peptidase-4 inhibitors versus sulfonylureas to metformin therapy in patients with type 2 diabetes mellitus. Ann Inter Med. 2015;163:663-672. doi:10.7326/M15-0308.

Commentary: This is an excellent example of a “real-world study” using an observational design to answer an important real-world question. Metformin is the recommended first-line therapy for type 2 diabetes, but questions remain as to the optimal choice of the next agent to add. The most commonly used class of medication after metformin remains the sulfonylureas, though they cause weight gain and a high risk of hypoglycemia, which has been linked to adverse cardiovascular (CV) outcomes.¹ The DPP-4 class is weight-neutral, and carries a low risk of hypoglycemia, and so may offer important advantages as the next choice of medication after metformin. This observational trial used a large comprehensive insurance database to compare outcomes of all patients started on a sulfonylurea vs those started on a DPP-4 and convincingly showed an important benefit in decreasing CV outcomes in patients on DPP-4 medications. —Neil Skolnik, MD

1. McCoy R, Shah ND, Van Houton HK, Wermers RA, Ziegenfuss JY, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care 2012;35:1897–1901.

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