Effects of sodium-glucose cotransporter 2 inhibitors on coronary microvascular dysfunction in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

Coronary microvascular dysfunction (CMD) is an important contributor to myocardial ischemia and adverse cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). Although sodium-glucose cotransporter 2 (SGLT2) inhibitors provide established cardiovascular benefits, their effects on coronary microvascular function remain uncertain. Therefore, we performed a systematic review and meta-analysis to synthesize the available evidence. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to January 16, 2026. Randomized controlled trials (RCTs), cohort studies, and pre–post studies were included. The primary outcome was coronary flow reserve (CFR), while secondary outcomes included resting and stress myocardial blood flow (MBF) and angiography-derived coronary microcirculatory resistance (AMR). Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random-effects models. Eleven studies involving 687 participants (7 RCTs, 2 cohort studies, and 2 pre–post studies) were included. In between-group analyses, SGLT2 inhibitors did not significantly improve CFR in RCTs (SMD 0.16; 95% CI − 0.13 to 0.45; P = 0.267), whereas a significant improvement was observed in the cohort study (SMD 0.69; 95% CI 0.28 to 1.09; P = 0.001). In within-group analyses, CFR increased significantly following treatment with SGLT2 inhibitors in RCTs (SMD 0.35 95% CI 0.06 to 0.64; P = 0.020) and the cohort studies (SMD 2.29; 95% CI 1.79 to 2.79; P < 0.001), but not in pre–post studies (SMD 0.41; 95% CI − 1.66 to 2.48; P = 0.696). Exploratory subgroup analyses suggested that treatment effects might vary according to SGLT2 inhibitors type and treatment duration; however, these findings were based on limited data and should be interpreted with caution. Resting and stress MBF did not change significantly in either between-group or within-group analyses (all P > 0.05). Only one study evaluated AMR and reported a reduction following SGLT2 inhibitors treatment, although the evidence remains limited. Sensitivity analyses supported the robustness of the pooled estimates, and no evidence of publication bias was detected. Current evidence does not demonstrate a significant improvement in CFR with SGLT2 inhibitors compared with control in RCTs. Although within-group analyses suggested improvements in CFR after SGLT2 inhibitors treatment, these findings should be interpreted cautiously because they were not consistently supported by between-group comparisons. Exploratory subgroup findings and the limited evidence for AMR require confirmation. Overall, SGLT2 inhibitors may have the potential to improve coronary microvascular function, but larger, well-designed RCTs are needed to establish their effects.