Endocrine Abstracts

Background: The PCSK9 inhibitors (PCSKi), evolocumab and alirocumab, were approved by NICE in 2016, and have since proved to be efficacious in lowering LDL-C. Yet little is known about their long-term adverse effects. Genetic studies have shown patients with PCSK9 loss-of-function variants are at increased risk of T2DM. Similarly, analyses of an adverse event database found increased reports of PCSK9i-related hyperglycaemia. Meta-analyses have suggested that PCSK9i increase fasting blood glucose and HbA1c; but have not shown increased incidence of new-onset diabetes, a result that was attributed to the short duration of the follow-up.

Aims: To establish whether long-term use of PCSK9i a) maintains LDL-C reductions b) is associated with increased HbA1c and new-onset diabetes.

Methods: This was a retrospective audit of non-diabetic, lipid clinic patients, initiated on PCSK9i between June 2016 to November 2020 at UHB Trust. HbA1c and LDL-C laboratory values were analysed for 1-5 years following initiation.

Results: Spearman’s correlation showed % LDL-C change was unaffected by duration of PCSK9i treatment (n=135, r=0.0493, 95% CI: -0.126 to 0.221, P=0.2850). Overall mean reduction in LDL-C was -59.4%, over a mean duration of 4.45 years. Paired t-tests showed pre/post LDL-C changes were significant for evolocumab, and alirocumab. A mixed-effects model for repeated measures data was used to investigate an association between duration of PCSK9i therapy and HbA1c. Cumulative increases in HbA1c from second to fifth year were found for evolocumab, but not alirocumab, and the increase was significant at five years of treatment (mean difference between HbA1c before evolocumab vs. after 5 years: -2.456, CI: -3.788 to -1.124, P=0.0002). The incidence of new-onset diabetes in patients on PCSK9i was 1.48% during follow-up.

Conclusion: PCSK9 inhibitor treatment sustained significant reductions in LDL-C over the long-term. At five years of treatment, evolocumab, but not alirocumab, was found to significantly increase HbA1c.