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
BMJ 2016; 355 doi: https://doi.org/10.1136/bmj.i5340 (Published 20 October 2016) Cite this as: BMJ 2016;355:i5340
- Blánaid M Hicks, postdoctoral fellow1 2,
- Hui Yin, statistician1,
- Oriana H Y Yu, endocrinologist1 3,
- Michael N Pollak, professor of oncology4 5,
- Robert W Platt, professor of biostatistics1 2 6 7,
- Laurent Azoulay, associate professor of epidemiology and oncology1 2 4
- 1Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montréal H3T 1E2, Canada
- 2Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal
- 3Division of Endocrinology, Jewish General Hospital
- 4Gerald Bronfman Department of Oncology, McGill University
- 5Segal Cancer Center, Lady Davis Institute for Medical Research, Jewish General Hospital
- 6Department of Pediatrics, McGill University
- 7Research Institute of the McGill University Health Centre, Montreal
- Correspondence to: L Azoulay laurent.azoulay{at}mcgill.ca
- Accepted 23 September 2016
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.
Design Population based cohort study.
Setting Clinical Practice Research Datalink, UK.
Participants 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.
Main outcomes and measures 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.
Footnotes
Contributors: All authors conceived and designed the study, analysed and interpreted the data, and critically revised the manuscript for important intellectual content. LA acquired the data. BMH, HY, RWP, and LA did the analyses. BMH wrote the manuscript and all authors participated in the interpretation of the results and critical revision of the manuscript. LA is the guarantor.
Funding: This study was funded by a foundation grant from the Canadian Institutes of Health Research. The sponsor had no influence on design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the Canadian Institutes of Health Research for the submitted work; RWP holds the Albert Boehringer I chair and is the recipient of a Chercheur-National career award from the Fonds de Recherche du Quebec-Santé (FRQS; Quebec Foundation for Health Research); RWP also reports personal fees from Pfizer, Novartis, Abbvie, and Amgen, outside the submitted work; LA is the recipient of a Chercheur-Boursier career award from the FRQS; all other authors have no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The study protocol was approved by the independent scientific advisory committee of the Clinical Practice Research Datalink (protocol number 16_096R) and by the research ethics board of Jewish General Hospital, Montreal, Quebec, Canada.
Data sharing: No additional data available.
The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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