Disclosure belangen NHG spreker (Potentiële) belangenverstrengeling Jetty A. Overbeek is a PhD student at the VUmc and is an employee of the PHARMO Institute for Drug Outcomes Research Voor bijeenkomst mogelijk relevante relaties met bedrijven The PHARMO Institute for Drug Outcomes Research is an independent research institute and performs financially supported studies for government and related healthcare authorities and several pharmaceutical companies Sponsoring of onderzoeksgeld Honorarium of andere (financiële) vergoeding Aandeelhouder Andere relatie, namelijk … Not applicable

Risk of dipeptidyl-peptidase-4 (DPP-4) inhibitors on site-specific cancer A systematic review and meta-analysis Jetty A. Overbeek, Marina Bakker, Amber A.W.A. van der Heijden, Myrthe P.P. van Herk-Sukel, Ron M.C. Herings, Giel Nijpels

Background DPP-4 inhibitors ► Type 2 Diabetes Mellitus DPP-4 involved in many physiological processes Concerns about pancreatic safety, especially pancreatic cancer In 2014, the Food and Drug Administration (FDA) & European Medicines Agency (EMA) did not yet reach a final conclusion regarding the possible relationship

Methods & Results Methods Results PubMed and EMBASE, Jan 2005 - Apr 2017 Inclusion criteria: DPP-4 inhibitor vs. placebo/other oral antidiabetic drug Original study (randomised controlled trials (RCTs) & observational) ≥1 site-specific cancer as outcome ≥52 weeks follow-up 25 studies included; 12 RCTs & 13 observational Sample size ranged from: 29 to 71,137 (DPP-4 inhibitors) 30 to 3,934,676 (comparators) Mean age ranged from 52 to 76 years Follow-up ranged from: 52 to 156 weeks (RCTs) 1.1 to 6.6 years (cohort studies) The databases PubMed and EMBASE were searched between Jan 2005 and June 2016 to identify intervention studies regarding DPP-4i and cancer risk. Studies were included if they reported on at least one cancer outcome and had a follow-up of at least one year after start drug use. Methodological quality of the studies was assessed and screening full-text assessment and data-extraction was performed. Sensitivity analyses were performed including studies with high quality.

Results RCTs Observational studies

Conclusion No association between DPP-4 inhibitors and an increased short-term risk of site-specific cancer Limitations Low number of studies Relatively short follow-up Methodological quality was low This meta-analysis shows that the use of DPP-4 inhibitors is not associated with an increased short-term risk of site-specific cancer compared to use of other non-insulin antidiabetic drugs. The number of included studies per cancer type was low and many studies suffered from methodological limitations. Duration of the included studies was relatively short and the effect of DPP-4 inhibitors on different cancer types remains unknown. More sound studies with long follow-up are necessary to truly assess the impact of DPP-4 inhibitors on risk of different types of cancer.