Abstract Background Diabetes mellitus accelerates atherosclerotic plaque progression, yet the comparative efficacy of glucose-lowering agents in mitigating this risk remains unclear. This study evaluates the differential effects of major antidiabetic drug classes on plaque progression in diabetic patients. Methods A retrospective cohort of patients undergoing serial coronary computed tomography angiography (CCTA) at our hospital (August 2011–May 2023) was analyzed. We included 885 diabetic patients (3,540 vessels) and performed Cox regression analyses at both patient- and vessel-levels. Outcomes included plaque progression defined by maximal stenosis (MAX), segment involvement score (SIS), and segment stenosis score (SSS). Adjusted models accounted for covariates including age, sex, and cardiovascular risk factors. Results At the vessel level, adjusted analyses demonstrated significant risk reduction with GLP-1 agonists (HR 0.52, 95% CI 0.36–0.77; p0.001), metformin (HR 0.77, 95% CI 0.59–0.99; p=0.039), and SGLT-2 inhibitors (HR 0.76, 95% CI 0.58–0.99; p=0.040) compared to DPP-4 inhibitors, while TZDs showed no benefit (HR 0.98, p=0.91). At the patient level, GLP-1 agonists consistently reduced plaque progression across MAX (HR 0.34, p=0.002), SIS (HR 0.34, p0.001), and SSS (HR 0.41, p0.001) outcomes. SGLT-2 inhibitors trended toward benefit in SSS (adjusted HR 1.23, p=0.055), whereas DPP-4 inhibitors were associated with increased MAX progression (HR 1.34, p=0.051). Conclusion GLP-1 agonists exhibited the strongest association with attenuated atherosclerotic plaque progression in diabetic patients, independent of glycemic control. Metformin and SGLT-2 inhibitors also demonstrated modest protective effects, while DPP-4 inhibitors and TZDs showed limited efficacy. These findings underscore the importance of drug-specific strategies in cardiovascular risk management for diabetes.
Zhang et al. (2025) studied this question.