Introduction and Objective: Statins are first-line lipid-lowering agents but increase the risk of incident diabetes mellitus (DM). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are an alternative, though real-world data on their diabetogenic risk are limited. We compared incident DM risk among users of PCSK9i and other lipid-lowering therapies.Methods: Using the TriNetX Global Collaborative Network, we identified patients aged ≥50 years with hyperlipidemia and no baseline DM. PCSK9i users were compared against statin, ezetimibe, or fenofibrate users. Propensity score matching balanced demographics, healthcare utilization, and comorbidities. The 5-year incident DM risk was evaluated using Cox proportional hazards models and Kaplan-Meier analysis.Results: After matching, 20,138, 23,650, and 27,025 pairs were analyzed for the statin, ezetimibe, and fenofibrate comparisons, respectively (mean age 64.4years; 49.3% female). PCSK9i use was associated with a significantly lower risk of incident DM compared with statins (HR 0.803, 95% CI: 0.754-0.855), ezetimibe (HR 0.891, 95% CI: 0.842-0.943), and fenofibrates (HR 0.523, 95% CI: 0.499-0.548).Conclusion: PCSK9i therapy is associated with a lower risk of incident DM compared to conventional lipid-lowering agents. These findings suggest PCSK9i may be a metabolically favorable lipid-lowering option for older patients at high risk for diabetes.
C. Hsu: None. S. Lo: None. N. Nigam: None. Y. Tu: None. H. Bhanderi: None. S. Gau: None.
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