Role of treatments for diabetes and hyperlipidaemia in risk and mortality of primary and secondary brain tumours

BackgroundIn vivo and observational studies suggest anti-hyperlipidaemic and -diabetic medications (fibrates and glitazones respectively) may have a role in primary prevention and progression of brain tumours by targeting PPAR- and -{gamma}, respectively. MethodsWe conducted a case-control and clinical cohort study within the UK Clinical Practice Research Datalink. We identified adults (aged 18 years+) with primary or secondary brain tumours diagnosed between 2000-2016 prescribed either fibrates or glitazones and identified four controls based on age, sex and drug exposure duration. Multivariable logistic regression analysis estimated an association between drug exposure and brain tumour status. Coxs survival models were used to look at risk of mortality. Results1,916 cases were prescribed a fibrate and 445 cases a glitazone. Our analyses showed little evidence of an association between fibrates and either risk or mortality of brain tumours (adjusted odds ratio for ever exposed PPAR- 0.98, 95% CI: 0.77, 1.23; adjusted hazard ratio for ever exposed 0.91; 95% CI: 0.76, 1.09). We observed a reduced risk with a per-year increase in exposure duration for glitazones (adjusted odds ratio 0.88, 95% CI: 0.81, 0.96, P=0.002) but no major mortality benefit (adjusted hazard ratio 0.99, 95% CI: 0.80, 1.23). ConclusionsOur results suggest longer duration exposure to glitazones is associated with a reduced risk of primary and secondary brain tumours but no large effect on mortality. We failed to find any strong evidence of a protective effect on risk or mortality for fibrate exposure. Further studies are required for replication and to provide more precise effect estimates. Key PointsO_LIRepurposing existing drugs that target PPAR- and -{gamma} receptors may have a role in prevention and progression of brain tumours. C_LIO_LIWe observed a reduced risk between duration of glitazones and both primary and secondary brain tumours but no major reduction on mortality C_LIO_LIWe observed no major reduction of risk or mortality with fibrates C_LIO_LIFuture studies need to be undertaken to ensure replication and obtain more precise estimates C_LI Importance of StudyThe incidence of brain tumours appears to be increasing with a growing impact on years of life lost. Therapeutic options are limited, either for primary prevention or to prevent mortality of disease once developed. We investigated whether two commonly prescribed families of drugs (fibrates and glitazones) could offer potential drug-repurposing options in reducing brain tumour incidence or progression as informed by previous in vivo and observational studies. Our analyses suggest that glitazones are associated with a decreased brain tumour risk. These results can help guide future research into drug re-repurposing for brain tumour treatment.