From the Research
There is currently no strong evidence that Repatha (evolocumab), a PCSK9 inhibitor, causes insulin resistance. While some earlier concerns existed about PCSK9 inhibitors potentially affecting glucose metabolism based on genetic studies, clinical trials and post-marketing surveillance have not demonstrated a significant impact on insulin sensitivity or diabetes risk 1. Repatha works by blocking PCSK9 proteins, allowing more LDL receptors to remain on liver cells, which helps remove LDL cholesterol from the bloodstream. This mechanism differs from statins, which have been associated with a small increased risk of diabetes.
Some studies have investigated the effects of other lipid-lowering agents on glucose metabolism, such as ezetimibe, which has been shown to improve glucose metabolism in patients with insulin resistance 2, 3. However, these findings are not directly applicable to Repatha, and the available evidence suggests that Repatha does not significantly alter insulin sensitivity 4, 5.
The most recent and highest quality study on Repatha, the FOURIER trial and its extension FOURIER-OLE, demonstrated that evolocumab significantly reduces the incidence of major cardiovascular adverse events, with a monotonic relationship between the reduction in clinical events and the diminution of LDL-c levels, even down to the lowest concentrations 1. The safety profile of evolocumab was excellent, also in patients with very low LDL-c levels.
Patients taking Repatha should continue regular monitoring of blood glucose levels as part of standard care, especially if they have pre-existing diabetes or risk factors, but the medication itself is not considered to significantly alter insulin sensitivity. The benefit of substantial LDL cholesterol reduction with Repatha generally outweighs any theoretical concerns about glucose metabolism for patients requiring intensive lipid-lowering therapy. Key points to consider include:
- Repatha's mechanism of action is distinct from statins and does not appear to increase diabetes risk
- Clinical trials have not demonstrated a significant impact on insulin sensitivity or diabetes risk
- Regular monitoring of blood glucose levels is still necessary, especially for patients with pre-existing diabetes or risk factors
- The benefit of LDL cholesterol reduction with Repatha outweighs theoretical concerns about glucose metabolism.