Lower Risk of Type 2 Diabetes Mellitus With PCSK9 Inhibitors Compared With Other Lipid-Lowering Agents Among Patients...

The purpose of this paper is to compare the risk of incident type 2 diabetes mellitus (T2DM) among patients with hyperlipidaemia treated with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors versus statins and other nonstatin lipid-lowering agents.

This target trial emulation study used a retrospective, propensity score-matched cohort design based on the TriNetX Global Collaborative Network. Adults (≥ 18 years) with hyperlipidaemia diagnosed between January 2015 and December 2024 were included. Patients with preexisting diabetes, malignancy, or death during follow-up were excluded. Three active-comparator analyses compared PCSK9 inhibitors with statins, ezetimibe and fenofibrates under a per-protocol framework. Propensity score matching (1:1) balanced demographics, comorbidities, BMI, lipid profiles and healthcare utilization. Incident T2DM was identified using ICD-10 codes and analysed. Multiple sensitivity analyses including intention-to-treat analysis were performed. In the main analysis model, PCSK9 inhibitor use was associated with a significantly lower risk of incident T2DM than statins (HR 0.815; 95% CI 0.764-0.869), ezetimibe (HR 0.919, 95% CI 0.867-0.974), and fenofibrates (HR 0.517; 95% CI 0.493-0.542). Findings were consistent across subgroups and sensitivity analyses. No significant difference was observed between different PCSK9 inhibitor modalities.

In this large-scale real-world cohort, PCSK9 inhibitors were associated with a lower risk of new-onset T2DM compared with other lipid-lowering therapies, supporting their metabolic safety and clinical use in patients at risk for diabetes.