Journal Article

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

Pollak, Michael N, Platt, Robert W, Azoulay, Laurent, Yin, Hui, Yu, Oriana H Y, Hicks, Blánaid M

2016

Overview

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.

• Publisher: BMJ Publishing Group LTD
• Subject: Aged / Bias / Breast cancer / Breast Neoplasms - chemically induced / Breast Neoplasms - epidemiology / Cancer therapies / Clinical medicine / Cohort analysis / Cohort Studies / Diabetes / Diabetes mellitus / Diabetes Mellitus, Type 2 - drug therapy / Dipeptidyl-Peptidase IV Inhibitors - adverse effects / Dipeptidyl-Peptidase IV Inhibitors - therapeutic use / Epidemiology / Family medical history / Female / Fibroblasts / Glucagon / Glucagon-like peptide 1 / Glucagon-Like Peptide 1 - analogs & derivatives / Glucose / Growth factors / Health risk assessment / Humans / Hypoglycemic Agents - adverse effects / Hypoglycemic Agents - therapeutic use / Hypotheses / Insulin / Latency / Mammography / Middle Aged / Population / Population studies / Population-based studies / Practice research / Prescription drugs / Risk Factors / Time Factors / Tumors / United Kingdom - epidemiology / Weight control