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Meta-Analysis
. 2025 Dec;57(1):2594355.
doi: 10.1080/07853890.2025.2594355. Epub 2025 Nov 30.

Ezetimibe and the risk of new-onset type 2 diabetes: a systematic review and meta-analysis

Areej S Albawa'neh  1 , Mais N Alqasrawi  1 , Zeina N Al-Mahayri  2 , Amal Albawaana  3 , Gamila Ahmed  4 , Rami H Al-Rifai  5 , Bassam R Ali  1   6
Affiliations
Meta-Analysis

Ezetimibe and the risk of new-onset type 2 diabetes: a systematic review and meta-analysis

Areej S Albawa'neh et al. Ann Med. 2025 Dec.

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.

Keywords: Statins; T2DM; diabetes mellitus; ezetimibe; lipids.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
PRISMA flow diagram for studies selection.
Figure 2.
Figure 2.
Forest plot of the risk of new-onset type 2 diabetes mellitus associated with moderate-intensity statin plus ezetimibe therapy compared with moderate-intensity statin monotherapy. Squares represent individual study relative risks (RRs) with 95% confidence intervals (CIs); square size reflects study weight. The diamond indicates the pooled RR (random-effects model), and the horizontal bar shows the 95% CI. No heterogeneity was observed (I2 = 0.0%, p = .835).
Figure 3.
Figure 3.
Forest plot showing the pooled relative risk of new-onset type 2 diabetes mellitus in patients receiving moderate-intensity statin therapy combined with ezetimibe compared with high-intensity statin monotherapy. Squares represent study-specific relative risks (RRs) with 95% confidence intervals (CIs); square size reflects study weight. The diamond indicates the pooled RR (random-effects model), with a 95% CI. No heterogeneity was observed (I2 = 0.0%, p = .670).
See this image and copyright information in PMC

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