title: Glucagon-like peptide-1 receptor agonists and heart failure in type 2 diabetes: systematic review and meta-analysis of randomized and observational studies.
abstract: BACKGROUND
  The effect of glucagon-like peptide-1(GLP-1) receptor agonists on heart failure remains uncertain. We therefore conducted a systematic review to assess the possible impact of GLP-1 agonists on heart failure or hospitalization for heart failure in patients with type 2 diabetes.
  
  
  METHODS
  We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov to identify randomized controlled trials (RCTs) and observational studies that addressed the effect of GLP-1 receptor agonists in adults with type 2 diabetes, and explicitly reported heart failure or hospitalization for heart failure. Two paired reviewers screened reports, collected data, and assessed the risk of bias. We pooled data from RCTs and observational studies separately, and used the GRADE approach to rate the quality of evidence.
  
  
  RESULTS
  We identified 25 studies that were eligible for our review; 21 RCTs (n = 18,270) and 4 observational studies (n = 111,029). Low quality evidence from 20 RCTs suggested, if anything, a lower incidence of heart failure between GLP-1 agonists versus control (17/7,441 vs. 19/4,317; odds ratio (OR) 0.62, 95 % confidence interval (CI) 0.31 to 1.22; risk difference (RD) 19 fewer, 95 % CI 34 fewer to 11 more per 1000 over 5 years). Three cohort studies comparing GLP-1 agonists to alternative agents provided very low quality evidence that GLP-1 agonists do not increase the incidence of heart failure. One RCT provided moderate quality evidence that GLP-1 agonists were not associated with hospitalization for heart failure (lixisenatide vs placebo: 122/3,034 vs. 127/3,034; adjusted hazard ratio 0.96, 95 % CI 0.75 to 1.23; RD 4 fewer, 95 % CI 25 fewer to 23 more per 1000 over 5 years) and a case-control study provided very low quality evidence also suggesting no association (GLP-1 agonists vs. other anti-hyperglycemic drugs: 1118 cases and 17,626 controls, adjusted OR 0.67, 95 % CI 0.32 to 1.42).
  
  
  CONCLUSIONS
  The current evidence suggests that GLP-1 agonists do not increase the risk of heart failure or hospitalization for heart failure among patients with type 2 diabetes.
authors.affiliation: Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Sheyu
authors.initials: S
authors.lastname: Li
authors.affiliation: Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Liu
authors.affiliation: West China school of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Deng
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.|Department of Anesthesia, McMaster University, Hamilton, ON, Canada.|The Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Busse
authors.affiliation: Norwegian Knowledge Centre for the Health Services, Oslo, Norway.|Department of Medicine, Innlandet Hospital Trust, Gjøvik, Norway.
authors.forename: Per Olav
authors.initials: PO
authors.lastname: Vandvik
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Wong
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.|Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, Canada.
authors.forename: Zahra N
authors.initials: ZN
authors.lastname: Sohani
authors.affiliation: Department of Hygiene and Dietetics, Jagiellonian University Medical College, Krakow, Poland.|Systematic Reviews Unit-Polish Cochrane Branch, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Malgorzata M
authors.initials: MM
authors.lastname: Bala
authors.affiliation: Internal Medicine Unit, Hospital Clinico FUSAT, Rancagua, Chile.
authors.forename: Lorena P
authors.initials: LP
authors.lastname: Rios
authors.affiliation: Department of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: German
authors.initials: G
authors.lastname: Malaga
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.|Department of Anesthesia, McMaster University, Hamilton, ON, Canada.|Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, USA.|Department of Anaesthesia & Pain Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Shanil
authors.initials: S
authors.lastname: Ebrahim
authors.affiliation: Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan, China.
authors.forename: Jiantong
authors.initials: J
authors.lastname: Shen
authors.affiliation: Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan, China.
authors.forename: Longhao
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan, China.
authors.forename: Pujing
authors.initials: P
authors.lastname: Zhao
authors.affiliation: The Second Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Qunfei
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Medical Administration, 363 Hospital, Chengdu, Sichuan, China.
authors.forename: Yingqiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.|Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
authors.affiliation: Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan, China. sunx79@hotmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D064887:Observational Studies as Topic; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: Glucagon-like peptide-1 receptor; Heart failure; Meta-analysis; Systematic review; Type 2 diabetes