Inclisiran May Pose Lower Diabetes Risk than Atorvastatin, Study Suggests

A new review and meta-analysis published in Frontiers in Pharmacology indicates that inclisiran (Leqvio), a novel small interfering RNA (siRNA) treatment, may have a lower risk of causing new-onset diabetes (NOD) compared to the widely used statin, atorvastatin (Lipitor). This finding is particularly significant because while statins are highly effective at lowering cholesterol, their impact on glycemic control and a potential link to NOD has been a known clinical consideration.

Comparing LDL-C Therapies and Diabetes Risk

Inclisiran is a subcutaneous injection used as an adjunct to diet and statin therapy to reduce low-density lipoprotein cholesterol (LDL-C) and, in turn, cardiovascular risk. It works by inhibiting the production of PCSK9, a protein that breaks down LDL receptors on the liver. The efficacy of inclisiran has been established in clinical trials, and its favorable safety profile regarding liver and muscle function has made it a promising alternative for patients who struggle with statin-related side effects.

However, a known side effect of statin therapy is its impact on glycemic control, with some studies showing an increased risk of NOD by up to 46%. This new study sought to clarify the comparative risk of inclisiran.

Study Methodology and Key Findings

The investigators performed a comprehensive analysis using two primary data sources: the FDA Adverse Event Reporting System (FAERS) database and a meta-analysis of 16 randomized controlled trials (RCTs) involving nearly 300,000 patients. They compared the risk of NOD among patients treated with inclisiran, atorvastatin, and evolocumab (a PCSK9 inhibitor).

The key findings were as follows:

FAERS Analysis: The pharmacovigilance analysis of the FAERS database found a strong positive association between atorvastatin and reports of type 2 diabetes. In contrast, inclisiran showed no statistically significant association with NOD.
Meta-Analysis: The meta-analysis further supported this finding, showing that the incidence of NOD was significantly higher in the atorvastatin groups (4.80%) compared to the placebo groups (4.74%). There were no statistically significant differences in NOD incidence between the inclisiran, evolocumab, and placebo groups.
Reticular Meta-Analysis: A more advanced analysis confirmed a higher incidence of NOD with atorvastatin compared to inclisiran, evolocumab, and placebo. The differences among inclisiran, evolocumab, and placebo were insignificant, suggesting that neither inclisiran nor evolocumab increases the risk of NOD.

Clinical Implications and Future Research

While the study has limitations, such as the unstandardized nature of the FAERS database, the combined evidence suggests a lower risk of NOD with inclisiran compared to atorvastatin. The study authors concluded that while inclisiran is a relatively new drug and requires larger, long-term follow-up studies, these initial findings are promising.

For pharmacists and healthcare providers, this information is crucial for patient counseling. It provides confidence that inclisiran can be used to effectively lower LDL-C and improve cardiovascular risk without increasing the incidence of NOD. However, it is still recommended that glycemic parameters be monitored during treatment.