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

Abstract

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.

Sitagliptin reduces plaque macrophage content and stabilises arteriosclerotic lesions in Apoe −/− mice

“…For example, sitagliptin monotherapy significantly decreases triacylglycerol as well as NEFA levels and increases HDLcholesterol in patients with type 2 diabetes [11]. Furthermore, a significant decrease in systolic blood pressure could be shown with sitagliptin in non-diabetic patients with mild to moderate hypertension [12].…”

Cardiovascular Effects of Dipeptidyl Peptidase-4 Inhibitors: From Risk Factors to Clinical Outcomes

“…Nevertheless, sitagliptin has some more specific data. It produced small but statistically significant reductions of 2-3 mmHg in 24-hour ambulatory BP measurements in nondiabetic patients with mild to moderate hypertension 64 . Sitagliptin also lowered systolic BP without reducing body mass index, independent of the blood glucose reduction, in Japanese hypertensive patients with T2DM 67 .…”

“…Overall, DPP-4 inhibition may contribute to a small reduction in BP, although the effect was less marked than with GLP-1 receptor agonists (exenatide, liraglutide) [63][64][65] . In most phase 2-3 trials with DPP-4 inhibitors, no consistent effect on BP (systolic BP : −0.1; 95% CI −1.2 to +0.8 mmHg) has been recorded 66 .…”

“…Impaired insulin secretion Increased (glucose-dependent) insulin secretion 39 Increased glucagon levels Decreased (glucose-dependent) glucagon levels 39 Increased hepatic glucose production Decreased hepatic glucose production 39 Hyperglycemia Reduction in fasting and postprandial glycemia 50,51 Reduction in HbA1c 21,42 Body weight excess Weight neutrality (or small reduction) 21,27 Elevated blood pressure Modest reduction or no change in blood pressure 62,64,67 Dyslipidemia Reduction in postprandial lipemia 74,76,77,79 Mild improvement in fasting lipid profile 81 Silent inflammation Reduction in inflammatory markers (hs-CRP, IL-6, IL-18) 85,86 Oxidative stress Reduction in nitrotyrosine 53,86 Endothelial dysfunction Improved flow-mediated dilation 78,93,94 Platelet hyperactivity Reduction of platelet aggregation 99 …”

Incorporating Incretin-Based Therapies Into Clinical Practice: Differences Between Glucagon-Like Peptide 1 Receptor Agonists and Dipeptidyl Peptidase 4 Inhibitors

“…In a study of 19 patients with mild-tomoderate hypertension but without DM who were taking stable antihypertensive medication, 5 days of sitagliptin produced significant but small reductions in 24-hour systolic BP (-2.0 to -2.2 mm Hg) and diastolic BP (-1.6 to -1.8 mm Hg) compared with placebo (P<.05). 83 Saxagliptin or placebo was added to metformin therapy for 24 weeks in 743 patients with type 2 DM. Mean changes in fasting lipid levels were reported to be the same in the saxagliptin and metformin group compared with the placebo and metformin group.…”