title: Glucagon-like peptide-1 analogues and risk of breast cancer in women with type 2 diabetes: population based cohort study using the UK Clinical Practice Research Datalink.
abstract: OBJECTIVE
  To determine whether the use of glucagon-like peptide-1 (GLP-1) analogues, compared with the use of dipeptidylpeptidase-4 (DPP-4) inhibitors, is associated with an increased risk of incident breast cancer in patients with type 2 diabetes.
  
  
  METHODS
  Population based cohort study.
  
  
  METHODS
  Clinical Practice Research Datalink, UK.
  
  
  METHODS
  44 984 women aged at least 40 years, who were newly treated with glucose lowering drugs between 1 January 2007 and 31 March 2015, with follow-up until 31 March 2016.
  
  
  METHODS
  Time varying use of GLP-1 analogues compared with use of DPP-4 inhibitors, with exposures lagged by one year for latency purposes. Time dependent Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% confidence intervals of incident breast cancer associated with use of GLP-1 analogues overall, by cumulative duration of use, and time since initiation.
  
  
  RESULTS
  The cohort was followed for a mean of 3.5 years (standard deviation 2.2), with 549 incident events of breast cancer recorded (crude incidence 3.5 (95% confidence interval 3.3 to 3.8) per 1000 person years). Overall, compared with use of DPP-4 inhibitors, use of GLP-1 analogues was not associated with an increased risk of breast cancer (incidence 4.4 v 3.4 per 1000 person years; hazard ratio 1.40 (95% confidence interval 0.91 to 2.16)). Hazard ratios gradually increased with longer durations of use, with a peak between two to three years of GLP-1 use (2.66 (95% confidence interval 1.32 to 5.38)), and returned closer to the null after more than three years of use (0.98 (0.24 to 4.03)). A similar pattern was observed with time since initiation of GLP-1 analogues.
  
  
  CONCLUSIONS
  In this population based cohort study, use of GLP-1 analogues was not associated with an overall increased risk of breast cancer. Although it is not possible to rule out a tumour promoter effect, the observed duration-response associations are likely the result of a transient increase in detection of breast cancers in GLP-1 analogue users.
authors: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montréal H3T 1E2, Canada.|Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal.
authors: Blánaid M
authors: BM
authors: Hicks
authors: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montréal H3T 1E2, Canada.
authors: Hui
authors: H
authors: Yin
authors: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montréal H3T 1E2, Canada.|Division of Endocrinology, Jewish General Hospital.
authors: Oriana H Y
authors: OH
authors: Yu
authors: Gerald Bronfman Department of Oncology, McGill University.|Segal Cancer Center, Lady Davis Institute for Medical Research, Jewish General Hospital.
authors: Michael N
authors: MN
authors: Pollak
authors: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montréal H3T 1E2, Canada.|Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal.|Department of Pediatrics, McGill University.|Research Institute of the McGill University Health Centre, Montreal.
authors: Robert W
authors: RW
authors: Platt
authors: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montréal H3T 1E2, Canada laurent.azoulay@mcgill.ca.|Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal.|Gerald Bronfman Department of Oncology, McGill University.
authors: Laurent
authors: L
authors: Azoulay
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D052216:Glucagon-Like Peptide 1