SGLT2i use improves prognosis in T2D patients with coronary ischaemia

Use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduces 3-year risks of major adverse cardiac events (MACE) and all-cause mortality in patients with type 2 diabetes (T2D) and coronary ischaemia, irrespective of the completeness of revascularization, researchers from the University of Hong Kong (HKU) have reported.

“Patients with T2D and coronary ischaemia face an exceptionally elevated risk, and achievement of complete revascularization within this population can be challenging,” the researchers wrote. [Diabetes Metab J 2025;doi:10.4093/dmj.2025.0200]

Although guidelines of the American Diabetes Association and European Society of Cardiology recommend SGLT2i treatment in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), “SGLT2i’s real-world effectiveness in patients with T2D and coronary ischaemia, especially those at residual risk due to incomplete revascularization, remains unclear,” the researchers noted. [Diabetes Care 2025;48(Suppl 1):S27-S49; Eur Heart J 2023;44:4043-4140] “Compared with ASCVD patients, those with coronary artery disease with definite coronary functional ischaemia have a higher risk of cardiovascular [CV] events and mortality.”

In the current retrospective cohort study, the researchers evaluated 3-year clinical outcomes stratified by revascularization status and SGLT2i use in 671 patients (mean age, 69 years; male, 73 percent) with T2D and coronary ischaemia based on coronary angiography (CAG) conducted at Queen Mary Hospital between January 2014 and December 2016 as well as retrospective CAG-derived fractional flow reserve (caFFR) analysis.

Among the 671 patients included, 206 (30.7 percent) were SGLT2i users (ie, use of dapagliflozin or empagliflozin for ≥90 consecutive days during follow-up, irrespective of prior exposure). Complete revascularization of all major coronary artery lesions or segments exhibiting evidence of ischaemia on CAG or caFFR, irrespective of anatomical severity, was achieved in 484 patients (72.1 percent) after percutaneous coronary intervention, with no difference in rates between SGLT2i users and nonusers.

Reduced MACE & all-cause mortality at 3 years

Over a mean follow-up duration of 36 months, the primary endpoint of MACE (CV mortality, nonfatal MI, and heart failure [HF] hospitalization) occurred in significantly fewer SGLT2i users vs nonusers, translating to a 56.7 percent reduction in risk with SGLT2i (8.3 vs 17.8 percent; hazard ratio [HR], 0.433; 95 percent confidence interval [CI], 0.249–0.711; p=0.002).

The risk reduction in MACE with SGLT2i use vs nonuse was driven by a 75.6 percent risk reduction in CV mortality (1.5 vs 5.8 percent; HR, 0.244; 95 percent CI, 0.058–0.690; p=0.020) and a 56.6 percent risk reduction in HF hospitalization (5.3 vs 11.8 percent; HR, 0.434; 95 percent CI, 0.215–0.795; p=0.011). Nonfatal MI did not differ significantly between SGLT2i users and nonusers (2.4 vs 4.1 percent; HR, 0.592; 95 percent CI, 0.193–1.472; p=0.297).

All-cause mortality, a secondary endpoint, was likewise reduced significantly among SGLT2i users vs nonusers (6.3 vs 16.3 percent; HR, 0.360; 95 percent CI, 0.191–0.625; p<0.001) at 3 years.

Benefits irrespective of revascularization extent

“In this study, the rate of incomplete revascularization was high, at 27.9 percent, due to the complexity of coronary artery lesions in patients with T2D and the untreated ischaemic lesions identified using angiographic FFR,” the researchers pointed out. “This highlights the need for adjunctive pharmacological strategies to mitigate residual risk.”

Notably, SGLT2i’s effects in reducing MACE and all-cause mortality in the study’s high-risk population were not affected by the extent of revascularization, with benefits observed in both the complete and incomplete revascularization subgroups (p_interaction=0.804 for MACE; p_interaction=0.730 for all-cause mortality).

“In both the complete and incomplete revascularization subgroups, SGLT2i use was independently associated with MACE [reduction], with HR of 0.500 [95 percent CI, 0.245–0.947; p=0.042] and 0.351 [95 percent CI, 0.124–0.844; p=0.030], respectively, after adjustment for confounding factors,” the researchers reported.

Dual Tx strategy to mitigate residual risk

“While complete revascularization remains a cornerstone of managing coronary ischaemia due to its association with lower residual plaque burden and improved long-term outcomes, achieving complete revascularization is often hindered by complex lesion morphology and comorbidities,” the researchers explained.

They therefore proposed a dual strategy of pursuing complete revascularization where feasible and initiating SGLT2i early in patients with T2D and coronary ischaemia. “[This] offers a pragmatic approach to mitigating residual risk in this high-risk population,” they suggested.

“Even when complete revascularization cannot be achieved, SGLT2i offer robust CV protection, significantly improving survival outcomes. These agents provide a vital safety net when structural risks in the blood vessels persist,” said last author Professor Kai-Hang Yiu of the Department of Medicine, HKU, at a recent press conference.

Integrating caFFR with dual Tx

According to the researchers, some functionally important coronary artery blockages that appear mild on CAG may be overlooked in the absence of detailed functional assessment.

“Our study shows that functional assessment using caFFR allows clinicians to accurately identify blockages that truly cause ischaemia. This is crucial for achieving optimal revascularization in patients with T2D,” explained Yiu.