Diabetes Patients May Need Higher Doses of DPP4 Inhibitors

Patients with type 2 diabetes may need higher doses of dipeptidyl peptidase-4 (DPP4) inhibitors, according to a recent study.

In their study, the researchers analyzed data from 65 individuals involved in crossover studies that randomly assigned participants to either sitagliptin at 100 mg per day or sitagliptin at 200 mg or matching placebos. A total of 27 participants with type 2 diabetes and hypertension and 38 healthy controls were included in the studies. Fasting blood samples were obtained at baseline and 60 to 180 minutes after the administration of sitagliptin or placebo. DPP4 activity and antigen during placebo and sitagliptin and percent DPP4 inhibition during sitagliptin were assessed as the primary outcomes.
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Compared with healthy controls, sitagliptin at 100 mg per day was less effective at inhibiting DPP4 activity in individuals with type 2 diabetes and hypertension. Sitagliptin at 100 mg per day was not as effective as single dose sitagliptin at 200 mg in health controls. DPP4 activity during sitagliptin was associated with DPP4 genotypes rs2909451 TT and rs759717.

In addition, multivariable analyses showed DPP4 activity during sitagliptin was associated with type 2 diabetes with hypertension, sitagliptin dose, age, baseline systolic blood pressure, DPP4 activity during placebo, and rs2909451 genotype.

“Sitagliptin is less effective in inhibiting DPP4 in individuals with T2DM and hypertension than in healthy controls,” the researchers concluded. “Higher doses of DPP4 inhibitors may be required in patients with the metabolic syndrome.”

—Melissa Weiss

Reference:

Wilson JR, Shuey MM, Brown NJ, Devin JK. Hypertension and type 2 diabetes are associated with decreased inhibition of dipeptidyl peptidase-4 by sitagliptin [published online August 1, 2017]. J Clin Endocrinol Metab. https://doi.org/10.1210/js.2017-00312.