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Purpose <p>The comparative effects of non-insulin glucose-lowering therapies on coronary plaque progression in type 2 diabetes (T2DM) remain unclear. This study aimed to evaluate the impact of five major classes of non-insulin therapies on the progression of coronary atherosclerosis using serial coronary computed tomography angiography (CCTA).</p> Material and methods <p>This was a retrospective, registry-based cohort study analyzing 880 serial CCTA scans from patients with T2DM enrolled in the TOCCATA (Tomography of Coronary Artery Plaque and Treatment) registry. Patients were stratified based on their prescribed therapy: metformin (n = 357), dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 97), glucagon-like peptide-1 receptor agonists (GLP-1 RAs, n = 88), sodium-glucose cotransporter-2 inhibitors (SGLT2i, n = 258), and thiazolidinediones (TZDs, n = 80). The primary endpoints were vessel-level stenosis progression and changes in patient-level plaque scores, including the Maximum coronary stenosis score (MAXS), segment involvement score (SIS), and segment stenosis score (SSS). Multivariable Cox regression models, adjusted for relevant covariates, were used for the analysis.</p> Results <p>GLP-1 RAs were associated with the most significant reduction in vessel-level stenosis progression (adjusted Hazard Ratio [HR] 0.68, 95% Confidence Interval [CI]: 0.49–0.95, p = 0.024). This therapy class also consistently inhibited patient-level plaque progression across all scores (MAXS: HR 0.34, p = 0.002; SIS: HR 0.34, p &lt; 0.001; SSS: HR 0.41, p &lt; 0.001).In contrast, SGLT2i showed no significant effect on stenosis progression (HR 0.99, 95% CI: 0.82–1.19, p = 0.90) or SSS progression (HR 1.23, 95% CI: 1.00–1.52, p = 0.055). DPP-4 inhibitors showed a trend toward increased stenosis progression (HR 1.31, 95% CI: 1.01–1.69, p = 0.039). Metformin and TZDs had neutral effects on plaque progression.</p> Conclusion <p>In this real-world cohort of patients with type 2 diabetes, GLP-1 receptor agonists were associated with significantly slower coronary plaque progression compared to other glucose-lowering therapies. Other therapies, including SGLT2i, demonstrated no similar protective effects. These findings suggest that GLP-1 receptor agonists may offer particular benefits for patients with advanced atherosclerosis and underscore the potential value of CCTA in informing personalized therapeutic decisions in type 2 diabetes management.</p> Graphical abstract <p></p>

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Comparison of non-insulin glucose-lowering therapies on coronary atherosclerotic plaque progression in diabetes

  • 期刊论文

  • 发表日期：

    2026年7月24日

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  • Ran Liu,
  • Junyan Zhang,
  • Zhongxiu Chen,
  • Wenyu Huang,
  • Wanjiang Li,
  • Lin Shen,
  • Yujia Cai,
  • Yuting Lei,
  • Minggang Zhou,
  • Chen Li,
  • Li Rao,
  • Hongmei Yan,
  • Kaiyue Diao,
  • Yong He

摘要

Purpose

The comparative effects of non-insulin glucose-lowering therapies on coronary plaque progression in type 2 diabetes (T2DM) remain unclear. This study aimed to evaluate the impact of five major classes of non-insulin therapies on the progression of coronary atherosclerosis using serial coronary computed tomography angiography (CCTA).

Material and methods

This was a retrospective, registry-based cohort study analyzing 880 serial CCTA scans from patients with T2DM enrolled in the TOCCATA (Tomography of Coronary Artery Plaque and Treatment) registry. Patients were stratified based on their prescribed therapy: metformin (n = 357), dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 97), glucagon-like peptide-1 receptor agonists (GLP-1 RAs, n = 88), sodium-glucose cotransporter-2 inhibitors (SGLT2i, n = 258), and thiazolidinediones (TZDs, n = 80). The primary endpoints were vessel-level stenosis progression and changes in patient-level plaque scores, including the Maximum coronary stenosis score (MAXS), segment involvement score (SIS), and segment stenosis score (SSS). Multivariable Cox regression models, adjusted for relevant covariates, were used for the analysis.

Results

GLP-1 RAs were associated with the most significant reduction in vessel-level stenosis progression (adjusted Hazard Ratio [HR] 0.68, 95% Confidence Interval [CI]: 0.49–0.95, p = 0.024). This therapy class also consistently inhibited patient-level plaque progression across all scores (MAXS: HR 0.34, p = 0.002; SIS: HR 0.34, p < 0.001; SSS: HR 0.41, p < 0.001).In contrast, SGLT2i showed no significant effect on stenosis progression (HR 0.99, 95% CI: 0.82–1.19, p = 0.90) or SSS progression (HR 1.23, 95% CI: 1.00–1.52, p = 0.055). DPP-4 inhibitors showed a trend toward increased stenosis progression (HR 1.31, 95% CI: 1.01–1.69, p = 0.039). Metformin and TZDs had neutral effects on plaque progression.

Conclusion

In this real-world cohort of patients with type 2 diabetes, GLP-1 receptor agonists were associated with significantly slower coronary plaque progression compared to other glucose-lowering therapies. Other therapies, including SGLT2i, demonstrated no similar protective effects. These findings suggest that GLP-1 receptor agonists may offer particular benefits for patients with advanced atherosclerosis and underscore the potential value of CCTA in informing personalized therapeutic decisions in type 2 diabetes management.

Graphical abstract