PCSK9 Inhibition and Risk of Diabetes: Should We Worry?

Purpose of Review Since the clinical benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors occurs in a setting of reducing low-density lipoprotein-cholesterol (LDL-C) to unprecedentedly low levels, it becomes of interest to investigate possible adverse effects pertaining to the risk of new-onset diabetes (NOD). Recent Findings nWhile safety results reported in either meta-analyses or cardiovascular outcome trials FOURIER (with evolocumab) and ODYSSEY (with alirocumab) did not rise the incidence of NOD, Mendelian randomization analyses were almost concordant in showing an increased risk of NOD. This evidence was in line with post-marketing safety reports highlighting that evolocumab and alirocumab were primarily related to mild hyperglycaemia rather than diabetes, with most of the hyperglycaemic events occurring during the first 6 months of treatment. Summary Considering the different nature of genetic studies and of randomized controlled trials, with careful monitoring of patients, particularly in the earlier phases of treatment, and the identification of those more susceptible to develop NOD, treatment with PCSK9 inhibitors should be of minimal concern.

Automated summary

Considering the clinical benefit of PCSK9 inhibitors in reducing LDL-C to unprecedentedly low levels, it is important to investigate the possible adverse effects and the risk of new-onset diabetes. Recent studies have shown that while the safety results did not indicate an increase in the incidence of new-onset diabetes, Mendelian randomization analyses were almost consistent in showing an increased risk. Overall, with careful monitoring of patients and identification of those more susceptible to develop diabetes, treatment with PCSK9 inhibitors should be of minimal concern.