SGLT2 Inhibitors Research Articles

SGLT2 inhibitors increase low serum magnesium levels in patients with chronic kidney disease immediately after treatment.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown in clinical trials to increase serum Mg2+ levels in patients with type 2 diabetes mellitus. However, it is unclear whether this effect is similarly observed in patients with chronic kidney disease (CKD) and whether such an increase is observed immediately after treatment. Our retrospective observational study included the 62 patients with CKD who started SGLT2 inhibitor therapy at our institution between 2017 and 2022 and who had complete data on serum Mg2+ measurements at baseline and at 1, 3, and 6months after treatment. Patients were divided into three subgroups, stratified by serum Mg2+ levels at baseline. We evaluated the changes in serum Mg2+ levels from baseline to 6months after treatment and the factors associated with these changes. Median eGFR and mean serum Mg2+ at baseline were 33.5mL/min/1.73m2 and 2.03mg/dL, respectively. Treatment with SGLT2 inhibitors significantly increased serum Mg2+ levels immediately from 1month after treatment compared with those at baseline and persisted over 6months, with an overall mean change of 0.13mg/dL from baseline to 6months. This increased effect was observed in the low and middle tertile subgroups, but not in the high tertile subgroup. Multivariate linear regression analysis revealed that baseline serum Mg2+ levels and sodium-chloride differences, as a parameter of acid-base status, were independently associated with these changes. SGLT2 inhibitors increased serum Mg2+ levels in patients with CKD, particularly those with lower baseline Mg2+ levels, potentially improving their prognosis.

SGLT 2 Inhibitors: Mechanisms, Clinical Applications, and Future Directions

Due to the progressive and painful nature of type 2 diabetes (T2D), treatment may require periodic evaluation of patients, intensifying glucose-lowering therapy when glycaemic targets are not achieved and testing new methods. Among the newer classes of glucose-lowering drugs, sodium-glucose cotransporter 2 inhibitors (SGLT2is), which increase urinary glucose excretion to reduce hyperglycaemia, have made an impressive entry into the T2D treatment arsenal. Given their unique insulin-independent mode of action and favourable efficacy-adverse effect profiles, and their apparent benefits on cardiovascular-renal outcomes in intermediate-high-risk T2D patients, which have led to the updating of guidelines and product monographs, the role of this drug class in multidrug regimens is promising. However, despite much speculation based on pharmacokinetic and pharmacodynamic properties, physiological rationale and potential synergism, the glycaemic and pleiotropic effects of these agents when combined with other classes of glucose-lowering drugs remain largely under-researched. Therefore, this review discusses the mechanisms, clinical applications and future therapeutic role of SGLT2 inhibitors with a review of the literature.

SGLT2 inhibition improves coronary flow velocity reserve and contractility: role of glucagon signaling.

SGLT2 inhibitors, a T2DM medication to lower blood glucose, markedly improve cardiovascular outcomes but the underlying mechanism(s) are not fully understood. SGLT2i's produce a unique metabolic pattern by lowering blood glucose without increasing insulin while increasing ketone body and glucagon levels and reducing body weight. We tested if glucagon signaling contributes to SGLT2i induced improvement in CV function. Cardiac contractility and coronary flow velocity reserve (CFVR) were monitored in ob/ob mice and rhesus monkeys with metabolic syndrome using echocardiography. Metabolic status was characterized by measuring blood ketone levels, glucose tolerance during glucose challenge and Arg and ADMA levels were measured. Baysian models were developed to analyse the data. Dapagliflozin improved CFVR and contractility, co-application of a glucagon receptor inhibitor (GcgRi) blunted the effect on CFVR but not contractility. Dapagliflozin increased the Arg/ADMA ratio and ketone levels and co-treatment with GcgRi blunted only the Dapagliflozin induced increase in Arg/ADMA ratio but not ketone levels. Since GcgRi co-treatment only reduced the Arg/ADMA increase we hypothesize that dapagliflozin via a glucagon-signaling dependent pathway improves vascular function through the NO-signaling pathway leading to improved vascular function. Increase in ketone levels might be a contributing factor in SGLT2i induced contractility increase and does not require glucagon signaling.

Updated evidence on cardiovascular and renal effects of GLP-1 receptor agonists and combination therapy with SGLT2 inhibitors and finerenone: a narrative review and perspectives.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have a reliable hypoglycaemic and weight-loss effect that can intervene in obesity, which is the basis of type 2 diabetes pathology. GLP-1RA therapy has shown potential benefits in reducing the risk of major adverse cardiovascular events and improving kidney outcomes in patients with diabetes at high risk for cardiovascular disease. More recent evidence is expanding their benefits to heart failure with preserved ejection fraction and clinically important renal outcomes in patients with and without diabetes. Some sub-analyses of large clinical trials suggest that GLP-1RA and sodium-glucose cotransporter 2 inhibitor combination therapy may provide more significant reductions in heart failure hospitalization and renal composite events than each alone. Moreover, the addition of finerenone to this combination therapy could potentially provide stronger cardiorenal protective benefits. Further studies are needed to assess the potential cardiovascular and renal benefits of combination therapy and to determine suitable patient population for the therapy.

Triglyceride-glucose index and hsCRP-to-albumin ratio as predictors of major adverse cardiovascular events in STEMI patients with hypertension.

This study aimed to evaluate the association between the triglyceride-glucose (TyG) index and high-sensitivity C-reactive protein-to-albumin ratio (hsCAR) and the prognosis of patients with STEMI and hypertension. A total of 699 patients diagnosed with STEMI and hypertension were included in this study database. Compared to the low TyG index group (< 7.8), the high TyG index group (≥ 7.8) was associated with an increased risk of MACE (HR 2.09, 95% CI = 1.58-2.77; P < 0.001). Similarly, a higher hsCAR (≥ 0.15) was linked to an increased risk of MACE (HR 1.46, 95% CI = 1.12-1.90; P = 0.005). Subsequently, we categorized the population into four groups based on the defined cutoff points. Compared to the low TyG-low hsCAR subgroup, the other three subgroups demonstrated an elevated risk of MACE. Among patients treated with PCSK9 and SGLT2 inhibitors, the combined effect of the TyG index and hsCAR on MACE was attenuated. Finally, The combined TyG index and hsCAR model exhibited optimal performance (AUC = 0.71, 95% CI = 0.67-0.75; P < 0.001). This study demonstrates that the TyG index and hsCAR provide strong combined predictive power. The synergistic utilization offers a comprehensive approach to cardiovascular risk assessment.

Rhabdomyolysis and Sodium-Glucose-Linked Transport Inhibitors in Patients Taking Statins.

This case-control study investigates the risk of rhabdomyolysis among patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors.

Abstract 4138611: Impact of SGLT-2 Inhibitor Use on Atrial Fibrillation Incidence Following Heart Failure Hospitalization

Introduction: The development of atrial fibrillation (AF) in patients with heart failure (HF) is associated with increased morbidity and mortality. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have demonstrated cardiovascular benefit in patients with both preserved and reduced ejection fractions. Meta analysis of prospective trials suggest reduced incidence and burden of atrial fibrillation in patients taking SGLT-2 inhibitors, though this has not been specifically addressed in prospective trials. Hypothesis: SGLT-2 inhibitors reduce the incidence of atrial fibrillation in patients with heart failure. Aim: The goal of the study is to assess the impact of SGLT-2 inhibitor on the incidence of atrial fibrillation following heart failure hospitalization. Methods: The study included consecutive patients who were admitted to an academic tertiary care center over a 3 year time period with a primary diagnosis of heart failure exacerbation and no prior diagnosis of AF. The primary outcome was development of AF within 12 months after hospitalization. Demographic, comorbidity, echocardiographic data, and medications were obtained. Cox-regression analysis was performed to identify the predictors of new-onset AF after HF hospitalization. Results: Among the 3,953 patients included in our study, 704 (17.8%) patients were prescribed SGLT-2 inhibitors. Of those taking SGLT-2 inhibitors, 559 (79.4%) patients had diabetes. SGLT-2 inhibitor use is associated with significant reduction of AF at one year ( p&lt;0.001; RR 0.65; 95% CI: 0.51-.81 ). This finding was consistent across patients with reduced ejection fractions (EF&lt;50%) ( p=0.001; RR 0.56; 95% CI: 0.40-.80 ) and preserved ejection fraction (EF&gt;50%)( p=0.001; RR 0.58; 95% CI: 0.42-0.80 ). Conclusion: In patients with reduced ejection fraction and preserved ejection fraction heart failure, use of an SGLT-2 inhibitor is associated with a statistically significant lower risk of new-onset atrial fibrillation at one year following HF hospitalization.

Abstract 4122290: Association between SGLT2 inhibitors and risk of Dementia and Parkinson’s Disease: A Meta-analysis of 12 Randomized Controlled Trials.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated to reduce the risk of hospitalizations from heart failure and cardiovascular mortality. However, SGLT2i therapy’s potential effects on the risks of dementia and Parkinson’s disease are not well established, with conflicting results based on observational studies. Objective: We sought to evaluate the association between SGLT2i and the risk of dementia and Parkinson’s disease in patients with type 2 diabetes mellitus (T2DM), heart failure, or chronic kidney disease. Methods: We performed a systematic literature search on PubMed, Scopus, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until March 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model. Results: A total of 12 RCTs with 74, 442 patients (40784 in the SGLT2i group and 33658 in the control group) were included in the analysis. The mean age of patients in SGLT2i and control was 65.3 and 65.2 years respectively. The mean follow-up duration was 2.9 years. Pooled analysis showed that there is no significant association between SGLT2i and the risk of dementia (OR, 1.37 (95%CI: 0.70-2.69), P= 0.36, I2=0%), dementia Alzheimer’s type (OR, 2.62 (95%CI: 0.47-14.49), P= 0.27, I2=0), vascular dementia (OR, O.52 (95%CI: 0.09-2.98), P= 0.46, I2=0%), and Parkinson’s disease (OR, 0.75 (95%CI: 0.25-2.25), P= 0.61, I2=0%) was comparable between SGLT2i and control groups. Conclusion: Our study suggest that there is no significant association between SGLT2i and the risk of dementia, its subtypes, and Parkinson’s disease. Further large-power randomized trials are needed to strengthen the understanding of neuropsychiatric beneficial effects of SGLT2i.

Abstract 4134772: Optimizing Heart Failure with Preserved Ejection Fraction Management: Quality Review of SGTL2 Inhibitor Use

Heart failure with preserved ejection fraction (HFpEF) remains a diagnostic challenge despite a 50% incidence of HF admissions. H2FPEF tool is a validated scoring system that estimates HFpEF probability with a sensitivity of 69% and positive predictive value of 85%. Despite clinical research interest and therapeutic advances in HFpEF, implementation of therapies remain inconsistent. Currently ACC/AHA guidelines classify sodium-glucose cotransporter 2 inhibitors (SGLT2i) use a 2A recommendation with benefits for reducing hospital admissions. We assess the utilization of current guidelines. An observational retrospective analysis was performed of patients &gt;18 years with a left ventricular ejection fraction of &gt;50% seen in cardiology clinic with an ICD.10 code of diastolic heart failure from January 2022 to 2024 at a large tertiary hospital. Electronic records were reviewed for patient demographics, documentation of heart failure diagnosis, medication list and echocardiogram parameters. Primary outcome was HF related hospitalization. The study screened 79 patients, 51% females and 49% males. 20.2% of the patients were on SGLT2i, a quarter of which were female. Of those on SGLT2i, 56% were on diuretics, 81% had H2FpEF score &gt; 5, 56% had diabetes, and 19% had a HF hospitalization. SGLT2i was stopped in 1 patient due to cost. Of the (63) 79.8% of patients not on SGLT2I, 65% were on diuretics, 90% had H2FPEF score &gt; 5, 23% had diabetes and 32% had a HF hospitalization. 43% were males, with an average age of 71 for males and 62 for females. Ten patients had documented reasons for not being on SGLT2i including CKD, dialysis, yeast infection and denied insurance coverage. Unadjusted effect measures for HF hospitalization (HR 0.59, RRR 40.9%, OR 0.496; p 0.134). As guidelines are readily investigated and updated by expert consensus groups, evaluating practice patterns is key. Unlike other cardiac medications, SGLT2is are primarily initiated by cardiologists and recognizing barriers can identify generalizability of current guidelines. Our data looked at both objective and clinical endpoints for HFPEF diagnosis. Interestingly, women were less often started on SGLT2i and coverage was not a frequent cause for not using SGLT2i. Our quality metric analysis shows a potential protective effect of HF readmission with SGLT2i use in a highly symptomatic cohort, and suggests future directives need to focus on broadening educational reach among cardiologists.

Abstract 4113885: Impact of Sodium-glucose Cotransporter 2 Inhibitor on Recurrence and Cardiovascular Outcomes after Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure

Background: Catheter ablation for Atrial fibrillation (AF) has been proven to improve the prognosis in patients with heart failure (HF), while it remains a high risk for AF recurrence and adverse cardiovascular outcomes. The impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on these outcomes in HF patients after AF ablation is unknown. Method: HF patients with AF undergoing catheter ablation between January 2017 and December 2022 from the China-AF Registry were included. Patients were stratified into 2 groups based on the use of SGLT2i at discharge and were 1:1 matched by propensity score, with SGLT2i using (n=368) and non-SGLT2i using (n=368) in each group. The primary outcome was AF recurrence after a 3-month blanking period. Results: During a total of 1315 person-year follow-ups, AF recurrence occurred in 83 patients (22.6%) in the SGLT2i group and 132 patients (35.8%) in the non-SGLT2i group. SGLT2i was associated with a lower risk of AF recurrence (adjusted HR = 0.56, 95% CI: 0.43-0.74, P&lt;0.001). The composite risk of cardiovascular death, thrombotic events, or cardiovascular hospitalization was significantly lower in the SGLT2i group compared with those without SGLT2i (adjusted HR = 0.58, 95%CI: 0.41-0.80, p = 0.001). Although there was a tendency towards benefits, significant differences in all-cause mortality (adjusted HR = 0.76, 95%CI: 0.35-1.63, p = 0.480), cardiovascular mortality (adjusted HR = 0.62, 95%CI: 0.24-1.57, p = 0.312) and thrombotic events (adjusted HR = 0.40, 95%CI: 0.16-1.03, p = 0.056) were not noted between groups. Conclusion: The use of SGLT2i was associated with a lower risk of AF recurrence and the composite outcome of cardiovascular death, thrombotic events, or cardiovascular hospitalization after catheter ablation for AF in patients with HF.

Abstract 4135465: Efficacy of SGLT-2 inhibitors combined with percutaneous coronary intervention on clinical and echocardiographic parameters in patients with acute myocardial infarction: A systematic review and meta-analysis

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown benefits in improving cardiovascular outcomes in heart failure (HF) patients and may mitigate symptom progression in myocardial infarction (MI). However, their efficacy in acute MI patients undergoing percutaneous coronary intervention (PCI) is unclear. This study aims to evaluate whether SGLT2i combined with PCI improves clinical and echocardiographic outcomes. Methods: A comprehensive search of electronic databases, PubMed, Cochrane Central and SCOPUS was conducted from inception till May 2024. The study was conducted adhering to the PRISMA guidelines. The clinical benefit of PCI plus SGLT2i was assessed through risk reduction of acute kidney injury (AKI), CV death (CVD), hospitalization due to HF (hHF), all-cause mortality (ACM), and revascularization. Echocardiographic outcomes assessed were change in left ventricular ejection fraction (LVEF) and LV end-diastolic volume (LVEDV). Results were presented as risk ratios (RR) along with their 95% CI for dichotomous data while weighted mean difference (WMD) were reported for continuous outcomes. The data was aggregated using a random effects model. Results: Our analysis included eleven records comprising 6,411 participants. The results indicated that PCI plus SGLT2i significantly reduced the risk of AKI (RR: 0.66, 95% CI: [0.52, 0.83], p&lt;0.01) and ACM (RR: 0.54, 95% CI: [0.4, 0.7], p&lt;0.01) compared to PCI alone. However, the reduction in risk for CVD was not statistically significant (RR: 0.56, 95% CI: [0.2, 1.1], p=0.09), as was the case for hHF (RR: 0.65, 95% CI: [0.3, 1], p=0.07). Additionally, there was no significant difference in the risk of revascularization between the two groups (RR: 2.9, 95% CI: [0.62, 14.39], p=0.17). PCI plus SGLT2i was also significantly associated with an increase in LVEF (WMD: 2.73, 95% CI: [1.09, 4.36], p&lt;0.01) and decrease in LVEDV (WMD: -8.0, 95% CI: [-13.17, -2.90], p&lt;0.02). Conclusion: Our study demonstrates that SGLT2i administration in MI patients undergoing PCI leads to improved renal and mortality outcomes, along with enhanced cardiac function. These benefits are hypothesized to result from kidney-mediated natriuretic effects, improved blood flow regulation, reduced endothelial dysfunction, and decreased arterial stiffness, which optimize cardiac function. We recommend future studies with larger sample sizes and longer follow-ups to assess the long-term benefits of SGLT2i combined with PCI.

Abstract 4143220: Racial Differences in Prescription of SGLT2 Inhibitors and GLP1 Receptor Agonists Among US Veterans with Type 2 Diabetes and Coronary Artery Disease

Background: Clinical trials have demonstrated that sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) reduce cardiovascular (CV) risk in patients (pts) with type 2 diabetes (T2D) with or at high risk for CV disease. Adoption of new therapies has often lagged for Black pts compared with non-Hispanic White pts, contributing to poorer health outcomes. Methods: We identified Veterans with T2D and angiographic CAD between 2015 and 2020 at 84 Veterans Affairs (VA) medical centers who met eligibility criteria for the EMPA-REG OUTCOME or LEADER trials that first established the clinical efficacy of SGLT2i and GLP1RA, respectively. Within each cohort (SGLT2i- and GLP1RA-eligible), we used multivariable logistic regression adjusted for demographic and clinical covariates to estimate associations of race with evidence-based drug prescription. We evaluated patterns of evidence-based prescription of SGLT2i and GLP1RA over time and by race in US Veterans with T2D and coronary artery disease (CAD). Results: Of 63,561 pts with T2D and CAD, 3,527 Black and 18,668 White pts met trial eligibility criteria for SGLT2i treatment and 2,020 Black and 10,103 White pts for GLP1RA treatment. Evidence-based prescription of both classes increased over time for both races ( Figure ) but reached only approximately 40% for SGLT2i and 15% for GLP1RA in 2023. For SGLT2i, race (Black/White) was not associated with evidence-based prescription (adjusted odds ratio [OR] 0.96, 95% CI 0.89-1.04, P=0.3). However, Black pts were less likely than White pts to receive evidence-based prescription of GLP1RA (adjusted OR 0.85, 95% CI 0.74-0.98, P=0.025). Conclusions: Among pts with T2D and CAD in the VA healthcare system, evidence-based prescription of SGLT2i and GLP1RA increased over time, but many eligible pts remained untreated. Prescription of SGLT2i did not differ by race, but Black pts were less likely than White pts to have evidence-based prescription of a GLP1RA. Disparities in evidence-based use of CV treatments may be specific to certain drug classes, even in a healthcare system with few economic barriers. Further investigation is needed to determine underlying causes and solutions for such disparities.

Abstract 4129965: Efficacy of Sodium Glucose Cotransporter 2 Inhibitors In Patients With Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in patients with or without type 2 diabetes and heart failure (HF). However, studies have shown conflicting evidence regarding their efficacy in patients following acute myocardial infarction (MI). We conducted a systematic review and meta-analysis to synthesize the available evidence regarding the effectiveness of SGLT2 inhibitors in MI. Methods: A systematic literature search was conducted using PubMed/MEDLINE, the Cochrane Library, and Embase databases to identify randomized controlled trials (RCTs) that compared clinical outcomes of SGLT2 inhibitors with placebo following MI. We conducted the statistical analysis using RevMan, version 5.4, and pooled risk ratios (RRs) along the corresponding 95% confidence interval (CI) for all outcomes. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Results: Five RCTs reporting data for 11,211 patients were included in our study. Our pooled analysis showed that SGLT2 inhibitors significantly reduced the risk of hospitalizations for heart failure (HHF) (RR = 0.76, 95% CI: 0.61-0.88, p = 0.001; high certainty). In terms of absolute effects, this translated to 12 fewer HHF per 1,000 patients who received SGLT2 inhibitors compared with the placebo (absolute risk difference 12 (95% CI 17 to 5) fewer per 1000 patients) in patients with MI. However, the risk of all-cause mortality (RR = 1.05, 95% CI: 0.78-1.41, p = 0.76; high certainty), cardiovascular (CV) mortality (RR = 1.04, 95% CI = 0.84-1.29, p = 0.73; high certainty), and all-cause hospitalizations (RR = 1.06, 95% CI: 0.96-1.17, p = 0.25; high certainty) remained comparable across the two groups. Conclusion: SGLT2 inhibitors reduce HHF without affecting all-cause mortality, CV mortality, and all-cause hospitalizations. However, further evidence is required to reach a definitive conclusion.

Abstract 4117397: SGLT2i And Cardio-Renal Outcomes In Type 2 Diabetes Mellitus: A Systematic Review And Meta Analysis.

Background: Diabetes Mellitus (DM) significantly impacts global health through cardiovascular and renal complications. SGLT2 inhibitors (SGLT2i) have emerged as beneficial for cardiovascular outcomes in Type 2 Diabetes Mellitus (T2DM). However, only few studies report outcomes related to renal function. Aim: This study aims to analyse the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. Methods: A systematic review and meta-analysis, following PRISMA-2020 guidelines was conducted. We evaluated the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. We included randomized controlled trials(RCT) and post hoc analyses that compared SGLT2i with placebo, focusing on cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalizations, and renal outcomes such as the progression of albuminuria and the decline of eGFR. Dichotomous outcomes were calculated using relative risk (RR) with 95% confidence interval (CI). Results: We identified 2753 studies, registered in PubMed(=788), Embase(n=538), WoS(n=369), Scopus(n=908), and Cochrane(n=150). We included 11 studies 6 RCT and 7 Post Hoc Analysis, sample size of 50.653 patients. Meta-analysis showed that SGLT2i improve cardiovascular outcomes such as reduced cardiovascular mortality (RR 0.84 [95% CI 0.73–0.97] p=0.02), heart failure hospitalizations (RR 0.65 [95%CI 0.54–0.77]p&lt;0.00001), and their composites outcomes. Furthermore, renal outcomes with SGLT2i significantly improve Urinary Albumin-to-Creatinine Ratio (RR1.10 [95%CI 1.03–1.18]p=0.004), Improvement of the decline of the eGFR (RR1.08 [95%CI 1.04–1.11] p&lt;0.00001) and progression of albuminuria (RR 0.69[95%CI 0.66–0.72]p&lt;0.00001). Slower Doubling of serum creatinine (RR 0.71 [95% CI 0.61–0.82] p&lt;0.00001), end-stage kidney disease (RR 0.66 [95% CI 0.53–0.83] p=0.0003). Reduced Acute Kidney Injury (RR 0.72 [95% CI 0.58–0.89] p=0.002) and renal impairment (RR 0.57 [95% CI 0.34–0.95] p=0.03). Regarding death from renal causes, we identified a 46% relative reduction in the risk in SGLT2i group, although was not statistically significant (RR 0.54 [95% CI: 0.23, 1.27] p=0.16). The observed heterogeneity across studies calls for careful application of these results to individual patients. Conclusion: SGLT2i confers notable advantages in managing cardiorenal complications in T2DM, demonstrating a reduction in cardiovascular mortality and heart failure hospitalizations and offering a nephroprotective effect.

Abstract 4113561: Efficacy and Outcomes of Empagliflozin in Acute Coronary Syndrome Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated mortality benefits in patients with heart failure (HF). Since acute coronary syndrome (ACS) is an increasingly prevalent cardiovascular condition that often leads to HF, SGLT2i might play a role in reducing mortality in these patients. Previous randomized controlled trials (RCTs) have demonstrated inconsistent efficacy of Empagliflozin, an SGLT2i, in patients with ACS. Methods: A comprehensive systematic literature search was conducted spanning the major bibliographic databases to retrieve RCTs comparing Empagliflozin to placebo in patients with ACS. Odds ratios (OR) and mean differences (MD) with 95% confidence intervals were pooled using the DerSimonian and Laird random-effects model with statistical significance set at p&lt;0.05. Results: 5 RCTs were included with 7229 ACS patients (3608 in the Empagliflozin group and 3621 in the placebo group). Empagliflozin treatment was not associated with a statistically significant difference in all-cause mortality [OR: 0.94; 95% CI: 0.76, 1.17; p=0.60], cardiovascular death [OR: 1.00; 95% CI: 0.79, 1.28; p=0.99], hospitalization for heart failure [OR: 0.86; 95% CI: 0.42, 1.74; p=0.67], serious adverse events [OR: 1.85; 95% CI: 0.29, 11.87; p=0.51], LVEF on follow-up [MD: 4.35; 95% CI: -4.52, 13.23; p=0.34], NT-ProBNP [MD: -126.02; 95% CI: -279.37, 27.32; p=0.11], estimated glomerular filtration rate [MD: 1.59; 95% CI: -1.35, 4.52; p=0.29], and HbA1c [MD: -0.17; 95% CI: -0.53, 0.20; p=0.38] compared to placebo. Conclusion: This study concludes no statistical difference in all-cause mortality, cardiovascular death, and hospitalization for heart failure with empagliflozin therapy in ACS patients compared to placebo, however, the largest study (EMPACT-MI) had a statistically significant difference in hospitalizations for HF. Further large multicentric RCTs are warranted to validate these findings.

Abstract 4134267: Effects of GLP-1 Receptor Agonists and SGLT2 Inhibitors on In-Hospital Mortality and 30-Day Readmission in Type 2 Diabetic Patients with Acute Coronary Syndrome

Background: The effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2is) on reducing cardiovascular events in heart failure patients are well-established; however, less is known about their effects after a myocardial infarction. This study aims to investigate the effects of GLP-1RAs and SGLT2is on in-hospital mortality and 30-day readmission in type 2 diabetic patients with/without heart failure who were hospitalized for acute coronary syndrome (ACS). Methods: We conducted a multicenter retrospective cohort on type 2 diabetic patients who were admitted to the hospital for ACS from 01/01/2020 to 01/31/2024 across 16 West Florida hospitals. Patients receiving a GLP-1RA alone, SGLT2i alone, or both were compared to those taking neither. Chi-square and binary logistic regression were used to predict the clinical outcomes of in-hospital mortality, all-cause readmission within 30 days, and cardiac readmission within 30 days. Results: Among 7,481 type 2 diabetics with ACS, 392 (5.24%) were taking GLP-1RA monotherapy, 577 (7.71%) were taking SGLT2i monotherapy, 144 (1.92%) were taking both, and 6,362 (85.12%) were taking neither. The likelihood of in-hospital mortality was similar among patients on neither medication compared to patients on both (χ 2 = 0.06, p = 0.802), GLP-1RA monotherapy (χ 2 = 0.61, p = 0.435), and SGLT2i monotherapy (χ 2 = 0.002, p = 0.968). The odds of all-cause readmission within 30 days was similar among patients on neither medication compared to patients on both (χ 2 = 0.0004, p = 0.983), GLP-1RAs monotherapy (χ 2 = 0.07, p = 0.791), and SGLT2i monotherapy (χ 2 = 3.10, p = 0.078). The likelihood of cardiac readmission within 30 days was similar among patients on neither medication compared to patients on both medications (χ 2 = 1.63, p = 0.202), GLP-1RA monotherapy (χ 2 = 0.95, p = 0.329), and SGLT2i monotherapy (χ 2 = 0.94, p = 0.332). Conclusion: Our study found no significant differences in the odds of in-hospital mortality or 30-day readmission among type 2 diabetics with ACS who were taking GLP-1RAs, SGLT2is, or both, when compared to those taking neither. These findings further support the outcomes discovered in the EMPACT-MI trial.

Abstract 4134974: SGLT2 Inhibitors Following Acute Myocardial Infarction: A Systematic Review and Meta-Analysis

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits in various settings. However, their impact after myocardial infarction (MI) in patients without prior heart failure remains unclear. Therefore, we conducted a meta-analysis comparing SGLT2i to placebo in post-MI patients. Methods: We systematically searched Pubmed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing SGLT2i to placebo in post-MI patients. We calculated the Risk Ratio (RR) for binary outcomes and 95% confidence intervals (CI). Statistical analysis was performed using Review Manager 5.4. A random-effects model was used for all outcomes. Heterogeneity was examined with I2 statistics. Results: We included 3 RCTs comprising 11,065 patients in this meta-analysis, where 79.5% were male with a mean age of 61.9 years old. Two studies evaluated Empaglifozin and one Dapagliflozin. There was no statistically significant difference between groups in all-cause mortality (RR 1.05; 95% CI 0.78-1.41; p= 0.76; Figure 1A) and cardiovascular mortality (RR 1.04; 95% CI 0.84-1.29; p= 0.73; Figure 1B). There was a statistically significant reduction in the incidence of heart failure hospitalization in the SGLT2i group (RR 0.73; 95% CI 0.61-0.88; p&lt; 0.01; Figure 1C). Conclusion: Our systematic review and meta-analysis found that SGLT2i significantly reduced the incidence of heart failure hospitalization in patients following MI, without significantly affecting all-cause or cardiovascular mortality.

Sodium-glucose cotransporter 2 inhibition in patients with liver cirrhosis and diabetes: a possible role in ascites control?

The aim of this brief report is to evaluate sodium-glucose cotransporter 2 inhibitors (SGLT2-I) effects on patients with both refractory ascites and type 2 diabetes mellitus (T2D). We consecutively recruited all the diabetic patients with refractory ascites due to decompensated liver cirrhosis admitted between February and May 2023 at the Internal Medicine Unit of the University Hospital of Palermo. Clinical and laboratory data were collected after starting SGLT2-I therapy. SGLT2-I use was associated with a reduction/resolution of ascites and with an improvement in serum albumin and sodium levels and estimated glomerular filtration rate. SGLT2-I might represent a valid therapeutic option in the treatment of patients with refractory ascites and T2D, as already hypothesized by other research groups.

Abstract 4136724: Early Adoption of Sodium-Glucose Cotransporter-2 Inhibitor Among Patients Hospitalized with Heart Failure and Preserved Ejection Fraction in the United States

Introduction: In August 2021, the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) found that empagliflozin reduced rates of cardiovascular death and hospitalization by 21% in patients with heart failure with mildly reduced ejection fraction of 41-49% (HFmrEF) and with preserved ejection fraction of &gt; 50% (HFpEF). National trends in Sodium-Glucose Cotransporter-2 Inhibitors ( SGLT2i) use among patients with HFmrEF and HFpEF following this trial are unknown. Methods: We identified patients hospitalized for HFmrEF and HFpEF in the AHA Get With The Guidelines-Heart Failure registry between July 2021 and September 2023. We examined temporal trends in SGLT2i prescriptions at discharge after the publication of the EMPEROR-Preserved trial using the Cochran-Armitage trend test. Results: Among 158,849 hospitalizations with an EF &gt; 40% across 557 hospitals, 27,712 (17.4%) had HFmrEF, and 131,137 (82.6%) had HFpEF. Overall, 22,126 (13.9%) patients were discharged with a prescription for SGLT2i, with higher rates among those with HFmrEF (18.5% vs. 13.0% in those with HFpEF). Patients prescribed SGLT2i were more likely to be younger, male, of Black race, have type II diabetes, have Medicaid insurance, and be discharged from large hospitals. After publication of the EMPEROR-Preserved trial during Q3 2021, rates of SGLT2i prescription at hospital discharge increased from 4.2% in Q3 2021 to 23.5% in Q3 2023, with a 29% relative increase in the rate of SGLT2i prescription for each quarter (adjusted OR, 1.29 [95% CI: 1.28, 1.29]; P&lt;.001). Prescription rates increased from 6.1% in Q3 2021 to 31.6% in Q3 2023 among patients with HFmrEF and from 3.8% to 21.9% for patients with HFpEF (Figure). Conclusion: In the U.S., the use of SGLT2i at discharge has increased for patients hospitalized with HFmrEF and HFpEF following the publication of the EMPEROR-Preserved trial. However, the majority of eligible patients hospitalized for decompensated HF remain untreated with SGLT2i, indicating the need for further efforts to apply the scientific findings into clinical practice.

Abstract 4141446: Sodium Glucose Co-transporter 2 (SGLT2) Inhibitors Promote Resiliency to High Pressure Stress in the Human Microvasculature

Emerging evidence suggests that vascular stress from cardiovascular-related co-morbidities promotes microvascular dysfunction, a key component in the development of heart failure with preserved ejection fraction. The sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin has been shown to reduce both morbidity and mortality associated with heart failure with preserved ejection fraction, however the full scope of influence of this therapy on human microvascular function remains unknown. We hypothesized that pre-treatment of isolated human microvessels with empagliflozin will prevent stress-induced endothelial dysfunction as evidenced by preserving both the magnitude of flow-induced dilation (FID) as well as the ability to dilate to nitric oxide. Human resistance arterioles (80-250µm) from healthy adults (defined as patients with ≤1 risk factor for cardiovascular disease) were dissected from discarded surgical adipose tissue and treated with empagliflozin (1µM), or vehicle control (ethanol) for 16-20 hours prior to the flow experiment. Vessels were cannulated for videomicroscopy and subjected to high intraluminal pressure (150mmHg, 30 min), an acute stress known to induce endothelial dysfunction. Vessels were pre-constricted with endothelin-1 prior to initiation of flow. A nonlinear logistic regression was used to determine differences between curves. Compared to vehicle control, vessels pre-treated with empagliflozin (1µM ) exhibited nitric oxide-dependent FID as dilation was impaired in the presence of the nitric oxide synthase inhibitor L-NAME (EC50 Control: 10.7 vs L-NAME 83.45, p=0.0107). This data suggests that empagliflozin, an SGLT2 inhibitor, promotes microvascular resilience to stress via preservation of nitric oxide-mediated FID. The ability to elicit stress resilience may explain in part some of the cardiovascular benefits associated with SGLT2 inhibitors and may offer unique opportunities for early intervention or prevention of microvascular dysfunction associated with comorbidities that contribute to heart failure with preserved ejection fraction.