Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry

Abstract

Background The inflammatory response occurring in acute myocardial infarction (AMI) has been proposed as a potential pharmacological target. Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) for their pleiotropic beneficial effects. We tested the hypothesis that SGLT2-I have anti-inflammatory effects along with glucose-lowering properties. Therefore, we investigated the link between stress hyperglycemia, inflammatory burden, and infarct size in a cohort of type 2 diabetic patients presenting with AMI treated with SGLT2-I versus other oral anti-diabetic (OAD) agents. Methods In this multicenter international observational registry, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the presence of anti-diabetic therapy at the admission, patients were divided into those receiving SGLT2-I (SGLT-I users) versus other OAD agents (non-SGLT2-I users). The following inflammatory markers were evaluated at different time points: white-blood-cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), and C-reactive protein. Infarct size was assessed by echocardiography and by peak troponin levels. Results The study population consisted of 583 AMI patients (with or without ST-segment elevation): 98 SGLT2-I users and 485 non-SGLT-I users. Hyperglycemia at admission was less prevalent in the SGLT2-I group. Smaller infarct size was observed in patients treated with SGLT2-I compared to non-SGLT2-I group. On admission and at 24 h, inflammatory indices were significantly higher in non-SGLT2-I users compared to SGLT2-I patients, with a significant increase in neutrophil levels at 24 h. At multivariable analysis, the use of SGLT2-I was a significant predictor of reduced inflammatory response (OR 0.457, 95% CI 0.275–0.758, p = 0.002), independently of age, admission creatinine values, and admission glycemia. Conversely, peak troponin values and NSTEMI occurrence were independent predictors of a higher inflammatory status. Conclusions Type 2 diabetic AMI patients receiving SGLT2-I exhibited significantly reduced inflammatory response and smaller infarct size compared to those receiving other OAD agents, independently of glucose-metabolic control. Our findings are hypothesis generating and provide new insights on the cardioprotective effects of SGLT2-I in the setting of coronary artery disease. Trial Registration: Data are part of the ongoing observational registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT 05261867.

Sodium-Glucose Cotransporter-2 Inhibitors-from the Treatment of Diabetes to Therapy of Chronic Heart Failure

“…Preclinical studies on animal models of myocardial ischemiareperfusion injury showed that the use of gliflozins could be associated with a reduced infarct size [91]. These data were confirmed by the SGLT2-I AMI PROTECT observational registry [92]. Patients with type 2 diabetes and the acute coronary syndrome who were on chronic SGLT2 inhibitors presented with significantly lower levels of inflammatory parameters and a smaller size of myocardial necrosis compared to patients who were not treated with gliflozins.…”

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Urine Albumin to Creatinine Ratio in Type 2 Diabetes Mellitus Patients and Medication Care

“…Furthermore, except for lowering blood sugar [25][26][27][28][29][30], SGLT-2 inhibitors also had abilities to lose weight [24,31,32], reduce cardiovascular outcomes and mortality risk [33], and play renal protective effect [15]. It was also reported that SGLT-2 inhibitors could observably lower the response of inflammatory and smaller infarct size compared with other oral antidiabetic drugs, not dependent on blood sugar control [34]. In addition, as everyone knows, UACR, also known as urine microalbumin, helps identify kidney disease that could occur as a complication of diabetes [8].…”

Lower risks of sodium glucose cotransporter 2 (SGLT2) inhibitors compared to dipeptidyl peptidase-4 (DPP4) inhibitors for new-onset non-alcoholic fatty liver disease and hepatocellular carcinoma in type 2 diabetes mellitus: A population-based study

“…The protective effects of SGLT2I on the cardiovascular system are well-established [34][35][36][37]. For hepatic diseases, the literature generally supports the notion that SGLT2I and DPP4I are beneficial in hepatic diseases but lack direct comparisons.…”