PCSK9 Inhibitors: Are They OK for Diabetes Patients?

The newer cholesterol drugs known as PCSK9 inhibitors get dramatic results in patients who cannot take statins or for whom they don’t work. But physicians have raised concerns about prescribing PCSK9 drugs to patients with diabetes.

Writing in an editorial comment piece in The Lancet: Diabetes & Endocrinology, Jooho Lee and Robert Hegele said the concerns range from potential worsening of glycemia to “unanticipated adverse outcomes” even though in the phase 2 and phase 3 studies of the cholesterol-lowering drugs about 23% of the participants had type 2 diabetes.

So far there have been no such reported problems in people with diabetes using PCSK9 drugs but the authors point out that when statins were new it took years before clinicians saw an associated risk of new-onset diabetes.

“Should we hedge our bets regarding diabetes risk with PCSK9 inhibitors? “ they asked.

The writers cite a study by Amand Schmidt and colleagues who looked at four PCSK9 single nucleotide polymorphisms (SNPs) and assessed 550,000 genotyped patients. The phenotypes included those related to fasting glucose, HbA1c, bodyweight and how they related to the odds ratio of having type 2 diabetes.

They found that when people lose the function of PCSK9 due to inherited genetic traits, they also had an increased risk of type 2 diabetes.

There appears to be a link. “PCSK9 variants that reduce LDL cholesterol and risk of coronary heart disease are associated with slightly increased risk of diabetes and related traits,” they wrote.

Extrapolating from that finding “suggests that pharmacological inhibition of PCSK9, as with pharmacological inhibition of HMG-CoA reductase by statins, might increase diabetes risk,” Lee and Hegele wrote.

That could be a premature conclusion, they noted, and it is also possible that diabetes risk in carriers of the PCSK9 variant is cumulative, and that a short exposure to PCSK9 inhibiting drugs would likely not be harmful.

“With the data available, we cannot yet say whether diabetes risk would result from all forms of PCSK9 inhibition,” they concluded, but vigilance is the recommended course as large, long-term PCSK9 studies’ outcomes progress over the next few years.

Their article is entitled “PCSK9 inhibition and diabetes: turning to Mendel for clues.”