title: Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: A systematic review and network meta-analysis.
abstract: OBJECTIVE
  To evaluate current evidence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood pressure, heart rate, and hypertension in patients with type 2 diabetes.
  
  
  METHODS
  Medline, Embase, the Cochrane library, and the website www.clinicaltrials.gov were searched on April 5th, 2014. Randomized-controlled trials with available data were included if they compared GLP-1RAs with placebo and traditional antidiabetic drugs in patients with type 2 diabetes with duration ≥ 12 weeks. Weighted mean difference for blood pressure and heart rate, odds ratio (OR) for hypertension were calculated by random-effect model. Network meta-analysis was performed to supplement direct comparisons.
  
  
  RESULTS
  Sixty trials with 14 treatments were included. Compared with placebo, insulin, and sulfonylureas, GLP-1RAs decreased systolic blood pressure with range from -1.84 mmHg (95% CI: -3.48 to -0.20) to -4.60 mmHg (95% CI: -7.18 to -2.03). Compared with placebo, a reduction in diastolic blood pressure was detected significantly only for exenatide-10 μg-twice-daily (-1.08 mmHg, 95% CI: -1.78 to -0.33). Exenatide (2 mg once weekly), liraglutide 1.2 mg once daily), and liraglutide (1.8 mg once daily) increased heart rate by 3.35 (95% CI: 1.23-5.50), 2.06 (95% CI: 0.43, 3.74), and 2.35 (95% CI: 0.94-3.76) beats/min versus placebo. This effect was evident compared with active control (range: 2.22-3.62). No significant association between incident hypertension and GLP-1RAs was detected, except for the association between exenatide-10 μg-twice-daily and sulfonylureas (OR, 0.40, 95% CI: 0.16, 0.82).
  
  
  CONCLUSIONS
  GLP-1RAs were associated with modest reduction on blood pressure, a slight increase in heart rate, yet no significant association with hypertension. Further investigation to explore mechanisms is warranted.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, 38 Xueyuan Road, Haidian District, Beijing 100191, China; Department of Preventive Medicine, College of Medicine, Shihezi University, Shihezi 832002, China. Electronic address: siyan-zhan@bjmu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.affiliation: National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Xi-Cheng District, Beijing 100050, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Preventive Medicine, College of Medicine, Shihezi University, Shihezi 832002, China.
authors.forename: Shuxia
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of orthopedics, Tianjin Fifth Central Hospital, Tianjing 300450, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, 38 Xueyuan Road, Haidian District, Beijing 100191, China; Shantou-Oxford Clinical Research Unit, Shantou University Medical College, Guangdong 515041, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, 38 Xueyuan Road, Haidian District, Beijing 100191, China; Department of statistics, Graduate School of Arts and Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Lishi
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Xiaochi
authors.initials: X
authors.lastname: Quan
authors.affiliation: Department of Endocrinology and Metabolism, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Linong
authors.initials: L
authors.lastname: Ji
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Siyan
authors.initials: S
authors.lastname: Zhan
mesh_terms: D001794:Blood Pressure / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D000069450:Liraglutide / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D014688:Venoms / Q000627:therapeutic use; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D013453:Sulfonylurea Compounds; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: Blood pressure; GLP-1 receptor agonists; Heart rate; Hypertension; Network meta-analysis; Type 2 diabetes