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
Menée au Royaume-Uni sur une cohorte de 44 984 patientes atteintes d'un diabète de type 2 traité par hypoglycémiant entre 2007 et 2015 (âge : supérieur ou égal à 40 ans ; durée moyenne de suivi : 3,5 ans), cette étude évalue, par rapport à l'utilisation d'inhibiteurs de la dipeptidylpeptidase-4, l'association entre l'utilisation d'analogues au GLP-1 (glucagon-like peptide-1) et le risque de cancer du sein
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.
BMJ 2016