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Effects of dipeptidyl peptidase-4 inhibitors on blood pressure in patients with type 2 diabetes

A systematic review and meta-analysis

Zhang, Xiaodana; Zhao, Qingyub

doi: 10.1097/HJH.0000000000000782

This review was undertaken to assess the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on blood pressure (BP) in patients with type 2 diabetes (T2DM). We searched three main databases (PubMed, Web of Science, and Scopus) for relevant articles. Randomized controlled trials which reported BP changes from baseline to study endpoint in patients with T2DM receiving treatment of DPP-4 inhibitors were included for analysis. Random effects models were used to measure the mean differences with 95% confidence intervals (CIs). Fifteen trials involving 5636 participants were identified. When compared with placebo or nontreatment, DPP-4 inhibitors achieved greater reductions for both SBP (mean difference, −3.04 mmHg; 95% CI, −4.37 to −1.72; P < 0.00001) and DBP (mean difference, −1.47 mmHg; 95% CI, −1.79 to −1.15; P < 0.00001). But the BP-lowering effects of sodium-glucose cotransporter 2 inhibitors were more significant than those of DPP-4 inhibitors for both SBP (mean difference, 4.44 mmHg; 95% CI, 2.67–6.22; P < 0.00001) and DBP (mean difference, 2.15 mmHg; 95% CI, 1.08–3.21; P < 0.00001). No significant differences in BP changes were shown between DPP-4 inhibitors with other antidiabetic agents including glucagon-like peptide 1 receptor agonists, pioglitazone, sulphonylureas, metformin, and α-glucosidase inhibitors. DPP-4 inhibitors may exert modest BP-lowering effects compared with placebo or nontreatment for patients with T2DM, but no significant BP improvement was seen with this drug class when compared with other antidiabetic medications.

aDepartment of Endocrinology, The Second Affiliated Hospital of Guangzhou Medical University

bIntensive Care Unit, Sun Yat-sen University Cancer Center, Guangzhou, China

Correspondence to Qingyu Zhao, Intensive Care Unit, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510060, China. Tel: +86 20 87343577; e-mail:

Abbreviations: ACE, angiotensin-converting enzyme; BP, blood pressure; CI, confidence interval; DPP-4, dipeptidyl peptidase-4; EXAMINE, The Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care; FPG, fasting plasma glucose; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HbA1c, glycated hemoglobin; MD, mean difference; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SAVOR-TIMI, The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarcation; SD, standard deviation; SGLT-2, sodium-glucose cotransporter 2; T2DM, type 2 diabetes; TECOS, The Trial Evaluating Cardiovascular Outcomes with Sitagliptin; TZD, thiazolidinedione

Received 18 July, 2015

Revised 5 September, 2015

Accepted 24 September, 2015

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