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Resolving drug effects from class effects among drugs for type 2 diabetes mellitus: more support for cardiovascular outcome assessments

M. Odette Gore, Darren K. McGuire
DOI: http://dx.doi.org/10.1093/eurheartj/ehr019 ehr019 First published online: 6 April 2011

This editorial refers to ‘Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study’, by T.K. Schramm et al. doi:10.1093/eurheartj/ehr077

As illustrated most recently by the controversy surrounding the myocardial infarction risk associated with rosiglitazone,1 substantial uncertainty remains regarding the effects of different glucose-lowering drug classes and, importantly, different drugs within each class on cardiovascular (CV) risk and mortality outcomes in patients with type 2 diabetes (T2DM). In the setting of the ongoing proliferation of anti-hyperglycaemic therapeutic classes and formulations with myriad therapeutic options for the treatment of T2DM presently available,2 this uncertainty has prompted regulatory agencies in both Europe and the USA to reassess the approval process for new T2DM medications, with changes focused primarily on excluding with a specified degree of statistical certainty incremental CV risk prior to new drug approval.3 Long-term randomized clinical outcome trials with both new and presently available medications are recommended, but not mandated. In the absence of definitive CV risk assessment from randomized trials for presently available drug classes and individual drugs within each class, critical analyses of existing databases are both imperative and informative.

In this context, Schramm et al. have now reported the results of a nationwide registry-based observational analysis of clinical outcomes associated with various insulin secretagogues each compared with metformin.4 While this is not the first study to evaluate outcomes with these drug classes comparatively, the observations are among the most robust published based on the very large sample of patients with drug choices largely free of selection bias, sufficient numbers of events ascertained to yield substantial statistical power to analyse outcomes for each insulin secretagogue individually, with additional stratification by history of previous myocardial infarction. The overall results …

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