Our retrospective cohort study provides novel insights into the therapeutic role of empagliflozin in Chinese populations with obesity and T2DM, a population at elevated risk for adverse outcomes. Over a 6-month treatment period, empagliflozin demonstrated significant improvements in both cardiovascular and renal parameters, further supporting its role as a key therapeutic option in this high-risk subgroup.

Adverse events were infrequent in this study, with hypoglycemia occurring in 3.6%, urinary tract infections in 3.4%, and diabetic ketoacidosis in 1.8% of patients. These findings are comparable to other studies investigating the safety profile of empagliflozin [9]. Besides, our findings demonstrated a significant reduction in SBP and DBP after 6 months of empagliflozin treatment, following an initial increase in the first week. These results align with previous research showing the antihypertensive effects of empagliflozin, which contribute to its cardioprotective profile [9]. The incidence of MACE was 8.4%, with myocardial infarction occurring in 3.0%, stroke in 2.6%, and cardiovascular death in 2.8% of the patients. These rates are comparable to previous real-world studies evaluating SGLT2 inhibitors in patients with T2DM with a high cardiovascular risk profile. For example, a study focusing on patients with high cardiovascular risk reported a similar range of MACE incidence to ours [20]. Obesity is a well-established risk factor that worsens cardiovascular outcomes in individuals with T2DM, contributing to increased MACE rates in this population [21]. In this study, a significant reduction in body weight was observed during the 6-month treatment period (p < 0.001). This finding aligns with other studies showing the weight-reducing effects of SGLT2 inhibitors, which are particularly beneficial for patients with obesity. Weight loss, although relatively modest in percentage, contributes to improved metabolic and renal outcomes, which are crucial in this population [22].

Importantly, the multivariate analysis identified that higher HbA1c levels and elevated DBP were independently linked to an increased risk of MACE. These results indicate that, although empagliflozin provides cardiovascular benefits, optimizing glycemic control and blood pressure management remains critical in reducing cardiovascular risk in this high-risk population. Our findings are consistent with previous research underscoring the need for multifactorial interventions to mitigate cardiovascular risk in individuals with T2DM. For instance, elevated HbA1c levels have been proven to markedly raise the likelihood of MACE in patients with T2DM, particularly those undergoing coronary artery bypass grafting, where higher HbA1c levels correlated with increased risks of both MACE and mortality [23]. Similarly, elevated DBP has also been recognized as an independent risk factor for MACE in patients with T2DM and coronary artery disease [24].

In addition to its cardiovascular benefits, empagliflozin demonstrated significant renal protection in our cohort, as evidenced by improved eGFR and reduced serum creatinine levels. Notably, only 1% of patients with obesity and T2DM progressed to ESRD during the study period, which highlights empagliflozin’s potential to slow the progression of renal disease in this high-risk population. This finding is consistent with earlier studies supporting the nephroprotective properties of empagliflozin. For example, the EMPA-KIDNEY trial confirmed that empagliflozin substantially decreased the risk of kidney disease advancement and the development of ESRD in patients with CKD, with or without diabetes [25]. Similarly, real-world evidence from a study in Singapore demonstrated a 33% reduction in the risk of developing ESRD in patients treated with SGLT2 inhibitors, with empagliflozin showing a sustained risk reduction across various stages of CKD [26]. The reduction in albuminuria observed in our study further supports the renal benefits of empagliflozin, consistent with findings from previous research. For instance, the EMPA-REG OUTCOME trial reported that empagliflozin significantly reduced albuminuria by 25% and 32% in patients with baseline micro- and macroalbuminuria, respectively, with these reductions sustained over long-term treatment [22]. However, it is important to approach the renal effects of empagliflozin with caution, as some studies have reported no significant improvement in albuminuria, highlighting variability in the drug’s impact on proteinuria in different populations [11].

Our multivariate analysis identified that elevated albuminuria and lower eGFR were independently linked to an elevated risk of CKD progression, highlighting the importance of early identification and intervention for renal risk factors in individuals with obesity and T2DM. These findings are consistent with prior studies, which have demonstrated that elevated albuminuria is a significant predictor of renal function decline and CKD progression. For instance, a systematic review emphasized that albuminuria, alongside serum creatinine and eGFR, is a critical indicator of cardiorenal outcomes and kidney disease progression in patients with T2DM [27]. Additionally, albuminuria has been closely linked to accelerated CKD progression, particularly among those with reduced eGFR. In a real-world cohort of patients with T2DM, those presenting with severely increased albuminuria (UACR > 300 mg/dL) and eGFR between 30 and 59 mL/min/1.73 m2 exhibited a 65.1% greater likelihood of progressing to a more advanced CKD stage compared to those with normal albuminuria [28].

Many studies have already explored the cardiovascular and renal effects of empagliflozin in patients with T2DM, including the landmark EMPA-REG OUTCOME trial, which demonstrated significant benefits in a broader population with T2DM, and also included a substantial proportion of participants with obesity [11]. Subgroup analyses based on this trial further demonstrated that empagliflozin consistently decreased cardiorenal events and mortality across different BMI categories, including Asians [12]. However, these analyses were derived from controlled clinical trial settings, which may not fully reflect real-world treatment patterns and patient characteristics. Real-world evidence specific to Chinese patients with both obesity and T2DM remains limited. Our study stands out from prior research by focusing specifically on patients with obesity and T2DM from China, a population that has not been comprehensively studied in previous real-world analyses. In addition, our research narrows its focus exclusively on the obese population, delivering more targeted findings that can inform clinical management in this high-risk group [29].

This study has several limitations that must be considered when interpreting the findings. First, as a retrospective cohort study, the potential for residual confounding cannot be ruled out, despite adjustments for several key variables in our multivariate analyses. Second, the relatively short follow-up duration of 6 months may limit the generalizability of our findings to longer-term outcomes. Future studies with extended observation periods are needed to fully elucidate the long-term effects of empagliflozin. Additionally, the single-center design may restrict the applicability of the results to other patient populations or healthcare settings.