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Effect of Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, on Blood Pressure in Nondiabetic Patients With Mild to Moderate Hypertension

From Merck Research Laboratories, Rahway, New Jersey (Mr Mistry, Ms Maes, Dr Davies, Dr Gottesdiener, Dr Wagner, Dr Herman), and Clinical Pharmacology Associates, Miami, Florida (Dr Lasseter).

The effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on ambulatory blood pressure was assessed in nondiabetic patients with mild to moderate hypertension in a randomized, double-blind, placebo-controlled, 3-period crossover study. Nineteen patients on stable treatment with antihypertensive agent(s) received sitagliptin 100 mg b.i.d., 50 mg b.i.d., or placebo for 5 days, with at least a 7-day washout interval between periods. Twenty-four-hour ambulatory blood pressure, including systolic blood pressure, diastolic blood pressure, and mean arterial pressure, were monitored on days 1 and 5. Relative to placebo on day 1, the mean difference in 24-hour systolic blood pressure was -0.9 mm Hg (90% confidence interval: -2.9 to 1.1; P = .46) with sitagliptin 50 mg b.i.d. and -2.8 mm Hg (90% confidence interval: -4.9 to -0.8; P < .05) with 100 mg b.i.d. On day 5, the mean difference in 24-hour systolic blood pressure was -2.0 mm Hg (90% confidence interval: -3.5 to -0.4; P < .05) with 50 mg b.i.d. and -2.2 mm Hg (90% confidence interval: -3.7 to -0.6; P < .05) with 100 mg b.i.d. relative to placebo. For 24-hour diastolic blood pressure, there were no between-group differences in mean 24-hour diastolic blood pressure on day 1. On day 5, sitagliptin 50 mg and 100 mg b.i.d significantly (P < .05) lowered mean 24-hour diastolic blood pressure by -1.8 mm Hg (90% confidence interval: -2.8 to -0.8) and -1.6 mm Hg (90% confidence interval: -2.6 to -0.7), respectively, relative to placebo. Sitagliptin produced small but statistically significant reductions of 2 mm Hg to 3 mm Hg in 24-hour ambulatory blood pressure measurements acutely (day 1) and at steady state (day 5), and was generally well tolerated in nondiabetic patients with mild to moderate hypertension.

Key Words: DPP-4 • incretin • sitagliptin • blood pressure

Address for correspondence: Gary A. Herman, MD, Department of Experimental Medicine, Merck Research Laboratories, RY34-A400, 126 East Lincoln Avenue, Rahway, NJ 07065; e-mail: gary_herman{at}merck.com.

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