Cinti Francesca, Morciano Cassandra, Guarneri Andrea, Cappannoli Luigi, Sorice GianPio, Gugliandolo Shawn, Capece Umberto, Splendore Amelia, Avolio Adriana, Mezza Teresa, Iozzo Patricia, Pontecorvi Alfredo, Calcagni Maria Lucia, Burzotta Francesco, D'Amario Domenico, Crea Filippo, Leccisotti Lucia, Giaccari Andrea
Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy.
Unità di Medicina Nucleare, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Cardiovasc Diabetol. 2025 Aug 31;24(1):351. doi: 10.1186/s12933-025-02912-4.
Cardiovascular (CV) outcome trials have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce CV mortality in type 2 diabetes (T2DM). We previously found that 4 weeks of SGLT2i treatment increased coronary flow reserve (CFR) by 30% and reduced epicardial adipose tissue (EAT) thickness by 19% in T2DM patients with stable coronary artery disease (CAD). However, long-term effects remain unclear. This pilot study aimed to assess the long-term impact of dapagliflozin on CFR and EAT thickness in T2DM patients with CAD.
Patients with T2DM and stable CAD were enrolled in the DAPAHEART trial, a single-center, 4-week, randomized (1:1 dapagliflozin 10 mg vs. placebo), double-blind, controlled study. At the end of the trial, placebo group patients also transitioned to dapagliflozin. CFR and EAT thickness were measured at baseline, after 4 weeks, and after 4 years using N-ammonia PET/CT.
CFR increased 34.4% after 4 years (from 2.15 ± 0.19 at baseline to 2.85 ± 0.26, p = 0.001) with 29.18% reduction in EAT thickness (p = 0.03). BMI decreased in all patients (p = 0.001), but changes in BMI and EAT thickness were not significantly correlated (R= 0.0662; p = 0.5), suggesting a weight-independent effect of dapagliflozin on EAT.
The 30% CFR improvement seen after 4 weeks of dapagliflozin persisted at 4 years, together with a significant reduction in EAT thickness, possibly explaining CFR improvement. Similar results in the placebo group after treatment strongly support a causal relationship and underscore the long-term CV benefits of dapagliflozin and its role in reducing CV risk in T2DM patients.
心血管结局试验表明，钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）可降低2型糖尿病（T2DM）患者的心血管死亡率。我们之前发现，在患有稳定冠状动脉疾病（CAD）的T2DM患者中，4周的SGLT2i治疗可使冠状动脉血流储备（CFR）增加30%，并使心外膜脂肪组织（EAT）厚度降低19%。然而，长期影响仍不清楚。这项前瞻性研究旨在评估达格列净对患有CAD的T2DM患者CFR和EAT厚度的长期影响。
患有T2DM和稳定CAD的患者参加了DAPAHEART试验，这是一项单中心、为期4周的随机（1:1达格列净10mg与安慰剂）、双盲、对照研究。在试验结束时，安慰剂组患者也改用达格列净。使用N-氨PET/CT在基线、4周后和4年后测量CFR和EAT厚度。
4年后CFR增加了34.4%（从基线时的2.15±0.19增加到2.85±0.26，p=0.001），EAT厚度降低了29.18%（p=0.03）。所有患者的体重指数（BMI）均下降（p=0.001），但BMI和EAT厚度的变化无显著相关性（R=0.0662；p=0.5），这表明达格列净对EAT的影响与体重无关。
达格列净治疗4周后CFR提高30%的效果在4年后持续存在，同时EAT厚度显著降低，这可能解释了CFR的改善。治疗后安慰剂组的类似结果有力地支持了因果关系，并强调了达格列净的长期心血管益处及其在降低T2DM患者心血管风险中的作用。
