SGLT2 Inhibitors Show Promise in Reducing Heart Plaque Build-up in Diabetes Patients: Study

The findings published in Cardiovascular Diabetology offer insights into the potential mechanisms underlying the observed cardioprotective effects of SGLT2i in previous cardiovascular outcome trials (CVOTs).

Sodium-glucose cotransporter-2 inhibitor (SGLT2i) is a novel oral drug for T2D treatment with demonstrated cardiovascular benefits in recent years. The medications are known for their glucose-lowering effects by promoting urinary glucose excretion. Previous studies in apolipoprotein E knockout mice have revealed that SGLT2i is linked with attenuated progression of atherosclerosis. Yet, it remains uncertain whether this effect extends to patients with type 2 diabetes mellitus and coronary atherosclerosis in real-world settings.

Against the above background, Tianhao Zhang, Capital Medical University, Beijing, China, and colleagues performed a longitudinal CCTA cohort study among type 2 diabetes patients with coronary atherosclerosis to assess the effects of SGLT2i on the progression of coronary atherosclerosis.

For this purpose, the researchers screened T2D patients who underwent ≥ 2 CCTA examinations using coronary computed tomography angiography (CCTA) at their center between 2019 and 2022.

Eligible patients had multiple study plaques, defined as non-obstructive stenosis at baseline and without intervention during consecutive CCTAs. Exclusion criteria included a CCTA time interval of fewer than 12 months, prior use of SGLT2 inhibitors, or initiation/discontinuation of SGLT2 inhibitors during consecutive CCTAs. PV and PAV were quantified for each study plaque using CCTA plaque analysis software. Patients and their plaques were categorized based on SGLT2 inhibitor therapy and compared using 1:1 propensity score matching (PSM) analysis.

The study revealed the following findings:

· The study included 236 patients (mean age 60.5 ± 9.5 years; 69.1% male) with 435 study plaques (diameter stenosis ≥ 50%, 31.7%).

· Following SGLT2i treatment for a median duration of 14.6 months, overall, non-calcified, and low-attenuation PV and PAV were significantly decreased, while calcified PV and PAV were increased.

· Reductions in overall PV, non-calcified PV, overall PAV, and non-calcified PAV were significantly greater in SGLT2i-treated than non-SGLT2i-treated plaques.

· PSM analysis showed that SGLT2i treatment was associated with higher reductions in overall PV (− 11.77 mm3 versus 4.33 mm3), non-calcified PV (− 16.96 mm3 versus − 1.81 mm3), overall PAV (− 2.83% versus 3.36%), and non-calcified PAV (− 4.60% versus 0.70%).

· The findings remained consistent when assessing annual changes in overall and compositional PV and PAV.

· Multivariate regression models demonstrated that SGLT2i therapy was associated with attenuated progression of overall or non-calcified PV or PAV, even after adjusting for cardiovascular risk factors, medications, and baseline overall or non-calcified PV or PAV, respectively.

· The effect of SGLT2i on attenuating non-calcified plaque progression was consistent across subgroups.

"The study involving T2DM patients showed that SGLT2i therapy significantly regressed coronary overall PV and PAV, primarily driven by a marked reduction in the non-calcified plaque component," the researchers concluded.

Reference:

Zhang, T., Gao, X., Chen, T. et al. Longitudinal assessment of coronary plaque regression related to sodium–glucose cotransporter-2 inhibitor using coronary computed tomography angiography. Cardiovasc Diabetol 23, 267 (2024). https://doi.org/10.1186/s12933-024-02368-y