The use of GLP-1 analogues was not associated with an overall increased risk of breast cancer in a population based cohort study, in the BMJ.

Data were obtained from the UK Clinical Practice Research Datalink on 44,984 women, aged 40 or over, who were newly treated with glucose lowering drugs between the beginning of January 2007 and the end of March 2015. (2007 was the year that the first DPP-4 inhibitor and GLP-1 agonist were licensed in the UK.) The cohort was followed up until the end of March 2016. Patients were considered unexposed to a diabetes therapy until they had been taking it for a year.

Patients were required to have at least a year of medical history on the database before their first prescription of hypoglycaemic drugs. Patients being treated with insulin were excluded as this was suggestive of advanced disease. Women with gestational diabetes and polycystic ovaries were also excluded, to ensure that all metformin prescriptions were for established diabetes.

The cohort was followed for a mean of 3.5 years. There were 549 incident diagnoses of breast cancer recorded; crude incidence 3.5 (95% CI: 3.3-3.8) cases/1,000 person years.

Overall, compared with the 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 1,000 person years; hazard ratio (HR) 1.4 (95% CI: 0.91-2.16).

HRs gradually rose with duration of GLP-1 analogue use, with a peak at 2-3 years; HR 2.66 (95% CI: 1.32-5.38) and returned closer to the null after more than three years’ use HR 0.98 (95% CI: 0.24-4.23).

The study authors conclude: ‘In this population based study, the use of GLP-1 analogues was not associated with an overall increased risk of breast cancer, providing some reassurance to patients and clinicians. While the observed duration-response associations might be compatible with a tumour promotor effect, they are likely a result of a transient increase in detection of breast cancers in GLP-1 analogue users.’

This study is consistent with the recently published LEADER trial, a prospective study of the GLP-1 analogue liraglutide.1 This also showed a transient increase in breast cancer detection in early treatment and no overall excess mortality over longer follow-up. The main endpoint of the LEADER study was to show that cardiovascular outcomes were improved, and this was demonstrated.

Dr Matthew Lockyer

Hicks MB, Yin H, Yu OHY et al. 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:i5340