Prognostic outcomes of SGLT2 inhibitors versus metformin in patients with type 2 diabetes and acute myocardial infarction

Background Although SGLT2 inhibitors (SGLT2i) and metformin are first-line treatments for T2DM, evidence comparing their cardiovascular outcomes in patients with acute myocardial infarction (AMI) remains limited. Purpose This study aimed to compare the major clinical outcomes after acute myocardial infarction between diabetic patients treated with SGLT2i and those treated with metformin. Methods Data were derived from a multicenter retrospective study across 82 hospitals in China. We enrolled patients with a confirmed diagnosis of T2DM who were hospitalized for AMI between January 2010 and March 2024, and were treated with either SGLT2i or metformin. Patients who received both medications, had severe renal disease, malignancy, severe heart failure (Killip class≥3), or were under 18 years of age were excluded. The main outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), including cardiac death, cerebral infarction, myocardial infarction, and revascularization, and net adverse clinical events (NACE), which is a composite of all-cause death, cerebral infarction, myocardial infarction, revascularization, and bleeding events. Secondary outcomes included individual components of MACCE and NACE. Inverse probability of treatment weighting (IPTW) was used to adjust for differences in clinical characteristics between the two groups. Multivariable Cox regression analyses were performed before and after weighting to evaluate the prognostic impact of different hypoglycemic agents. Results The final study population comprised 12,950 patients, of whom 7,641 were treated with metformin (Table 1). The metformin group had a higher proportion of female patients (37.7% vs. 32.1%), a slightly older mean age (64.53 ± 15.27 vs. 63.14 ± 11.90 years), and higher prevalences of cerebrovascular comorbidity. Before adjustment, the SGLT2i group had significantly lower rates of one-year MACCE and NACE than the metformin group. All baseline variables achieved balance after IPTW (all SMD < 0.1). Following adjustment, compared with the metformin group, the SGLT2i group had a reduced risk of one-year MACCE (adjusted hazard ratio [aHR] 0.79, 95% confidence interval [CI] 0.72–0.85, p < 0.001) and NACE (aHR 0.81, 95% CI 0.75–0.87, p < 0.001). However, there was no significant difference in bleeding risk between the two hypoglycemic agents (p > 0.05, Table 2). Conclusions In patients with type 2 diabetes mellitus and acute myocardial infarction, the use of SGLT2 inhibitors (SGLT2i) within a broader glucose-lowering regimen was associated with a lower risk of one-year MACCE and NACE, without a higher bleeding risk, when compared with the use of metformin. These findings suggest that SGLT2i may offer superior cardiovascular and survival benefits in this clinical setting.