No effect of PCSK9 inhibitor alirocumab on the incidence of diabetes in a pooled analysis from 10 ODYSSEY Phase 3 studies

Analysis found no evidence of an effect of alirocumab on transition to new-onset diabetes in 3448 subjects without diabetes at baseline with a follow-up period of 6–18 months, compared to either placebo or ezetimibe. Longer follow-up is needed to conclusively rule out an effect.

An editorial notes that these results are reassuring but there are limitations to the findings:

 

• Statin-associated diabetes risk was only accepted as robust after meta-analysis of mutiple trials- such meta-analyses accumulated >4000 incident diabetes cases, whereas the present analysis includes only 214 such events and over much shorter follow-up (6–18 months).

 

• Most of data from alirocumab studies came on top of maximally tolerated statin treatment and, if there are overlapping mechanisms by which statins and PCSK9 inhibitors increase diabetes risk, these may be masked by the design of the current trials.

 

• Study did not examine changes in weight or other metabolic parameters such as insulin, reported to be altered by statins.

 

• Currently only limited and contradictory genetic data for PCSK9 variants and diabetes risk exist.

 

It adds that ultimately, the results of several ongoing large-scale cardiovascular endpoint trials testing PCSK9 inhibitors in tens of thousands of patients over several years and reported over the next few years will be pivotal since these will also report treatments effects on diabetes risk.