title: Comparative cardiovascular safety of glucagon-like peptide-1 receptor agonists versus other antidiabetic drugs in routine care: a cohort study.
abstract: To evaluate the comparative cardiovascular disease (CVD) safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in head-to-head comparisons with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulphonylureas or insulin, when added to metformin, as used in 'real-world' patients with type 2 diabetes mellitus (T2DM).
  
  
  
  Within a large US commercial health plan database linked to laboratory test results, we identified three pairwise 1 : 1 propensity-score-matched cohorts of patients with T2DM aged ≥18 years treated with metformin who initiated a GLP-1 RA or a comparator, i.e. DPP-4 inhibitor (n = 35 534), second-generation sulphonylureas (n = 28 138) or insulin (n = 47 068), between 2005 and 2013. We examined the association between drug initiation and a composite CVD endpoint, comprising hospitalizations for acute myocardial infarction, unstable angina, stroke or coronary revascularization.
  
  
  
  During the course of 1 year, there were 13.9 and 13.7 CVD events per 1000 person-years among propensity-score-matched initiators of GLP-1 RAs versus DPP-4 inhibitors [hazard ratio (HR) 1.02; 95% confidence interval (CI) 0.84-1.24]; and 12.1 versus 14.0 events among initiators of GLP-1 RAs versus sulphonylureas (HR 0.86; 95% CI 0.69-1.08). The effect estimates for GLP-1 RAs versus insulin were sensitive to the adjustment for glycated haemoglobin, after which the HR was 1.01 (95% CI 0.73-1.41). Results were robust across several sensitivity analyses, including an as-treated analysis considering up to 8.7 years of follow-up.
  
  
  
  This large study, performing head-to-head comparisons of GLP-1 RAs with other antidiabetic agents in real-world patients, provides estimates of relative safety precise enough to exclude large differences in CVD risk and adds further understanding to results from recent clinical trials.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Patorno
authors.affiliation: Divisions of Cardiovascular and Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Everett
authors.affiliation: Clinical Research, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Goldfine
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Glynn
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Gopalakrishnan
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.|Division of Rheumatology, Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Kim
mesh_terms: D000328:Adult; D000789:Angina, Unstable / Q000453:epidemiology*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D009204:Myocardial Revascularization / Q000706:statistics & numerical data*; D057216:Propensity Score; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D020521:Stroke / Q000453:epidemiology*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D008687:Metformin; D013453:Sulfonylurea Compounds; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C517652:hemoglobin A1c protein, human
keywords: DPP-4 inhibitor; GLP-1 analogue; cardiovascular disease; insulin therapy; pharmaco-epidemiology; sulphonylureas