Ann Med. 2025 Dec;57(1):2594355. doi: 10.1080/07853890.2025.2594355. Epub 2025 Nov 30.
ABSTRACT
BACKGROUND: Statins reduce cardiovascular risk but may increase new-onset type 2 diabetes mellitus (NO-T2DM). Ezetimibe, a cholesterol absorption inhibitor, is often added to statins to improve lipid control, yet its impact on NO-T2DM remains uncertain.
OBJECTIVE: This systematic review evaluated moderate-intensity statin plus ezetimibe dual therapy versus high-intensity statin monotherapy for NO-T2DM risk.
METHODS: Five databases were searched to identify eligible studies. Random-effects meta-analyses generated pooled relative risks (RR) quantifying the effect of ezetimibe plus moderate-intensity statins on NO-T2DM. The Attributable Risk Fraction (ARF) was quantified utilizing the pooled estimate.
RESULTS: Ten observational studies and four clinical trials were included. In four cohort studies, ezetimibe plus moderate-intensity statin compared to high-intensity statin monotherapy was significantly linked to 18% reduced risk of NO-T2DM (pooled RR: 0.82; 95% CI: 0.77-0.87; I2 = 0.0%; p < 0.001). In three methodologically similar studies, compared to moderate-intensity statin monotherapy, adding ezetimibe to moderate-intensity statin dual therapy showed non-statistically (p > 0.05) significant 4% increased risk of NO-T2DM development (pooled RR: 1.04; 95% CI: 0.94-1.14, I2= 0.0%). Compared with patients receiving high-intensity statin therapy, 22% of NO-T2DM cases could potentially be averted with dual therapy (moderate-intensity statin plus ezetimibe). In four studies involving 5,072 patients on high-intensity statins who developed NO-T2DM, 1,115 patients (812-1,420) could have been prevented with ezetimibe plus moderate-intensity statin dual therapy.
CONCLUSION: Incorporating ezetimibe with moderate-intensity statins, rather than relying solely on high-intensity statins, may reduce the risk of NO-T2DM in patients with dyslipidemia and elevated cardiovascular disease risk.
PROSPERO REGISTRATION NUMBER: CRD42024518630.
PMID:41320800 | DOI:10.1080/07853890.2025.2594355