Effects Of SGLT2 Inhibitors Research Articles

Impact of Sodium-Glucose Co-Transporter 2 Inhibitors on Atrial Fibrillation Recurrence Post-Catheter Ablation Among Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is the most common cause of arrhythmia-induced cardiomyopathy. Effective management strategies include medical therapy for rate and rhythm control, catheter ablation (CA), and goal-directed medical therapy. Sodium-glucose co-transporter 2 inhibitors (SGLT2i), a novel class of antidiabetic drugs, have shown a promising impact in reducing cardiovascular events in diabetic and nondiabetic heart failure (HF) patients. It is unclear what impact SGLT2i use may have on AF recurrence following CA. To evaluate the effects of SGLT2i on preventing AF recurrence following CA and its impact on other cardiovascular outcomes. We performed a comprehensive literature search through multiple search engines (PubMed, Scopus, Web of Science, and Cochrane) to include eligible studies using the appropriate keywords until 10 April 2024. Our search yielded nine eligible studies with 16 857 patients. Our analysis reveals a significant reduction in AF recurrence after CA among patients receiving SGLT2i compared to non-SGLT2i medications (RR = 0.72, 95% CI [0.67-0.78], p < 0.00001). Additionally, SGLT2i therapy was associated with decreased all-cause hospitalizations and reduced risk of ischemic stroke. However, no significant difference in all-cause mortality was observed between SGLT2i and non-SGLT2i groups. Our study found that SGLT2 inhibitors significantly reduced AF recurrence post-CA in diabetic patients. Moreover, SGLT2i use was associated with lowered hospitalization and ischemic stroke risk. Though no significant difference in mortality was noted, the decrease in hospitalization suggests a possible favorable effect on cardiovascular events.

Lack of renoprotective effects by long-term PCSK9 and SGLT2 inhibition using alirocumab and empagliflozin in obese ZSF1 rats.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease (CVD). Despite the entry of sodium glucose cotransporter 2 (SGLT2) inhibitors, CKD persists as a medical challenge. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition reduces low-density lipoprotein (LDL)-cholesterol, a major risk factor of CVD. Interestingly, studies indicate that PCSK9 inhibition decreases proteinuria in kidney disease, complementing the reduced CVD risk. This study aimed to validate obese ZSF1 rats as a model for the renoprotective effects of PCSK9 and SGLT2 inhibition using alirocumab and empagliflozin for 15 wk. Obese rats revealed a significant reduction in measured glomerular filtration rate (mGFR) and increased urine albumin/creatinine ratio (UACR) during follow-up compared with lean controls. Alirocumab treatment resulted in a decline in mGFR and increased UACR compared with vehicle-treated obese rats. Immunohistochemistry showed increased fibrosis and inflammation in kidney tissue from obese rats treated with empagliflozin or alirocumab, whereas hepatic cholesterol and triglyceride levels were lowered compared with vehicle-treated obese rats. Although alirocumab lowered circulating free cholesterol levels throughout the treatment period, certain cholesteryl esters were increased at the end of the study, resulting in no overall difference in total cholesterol levels in the alirocumab group. Correspondingly, only a trend toward increased hepatic LDL-receptor levels was observed. In conclusion, these findings suggest that alirocumab treatment aggravates kidney dysfunction in obese ZSF1 rats. Moreover, in contrast to the renoprotective properties of empagliflozin observed in patients with CKD, empagliflozin did not ameliorate kidney disease progression in the obese ZSF1 rat.NEW & NOTEWORTHY New treatments to slow kidney disease progression and reduce cardiovascular disease risk are needed for chronic kidney disease (CKD). We investigated the cholesterol-lowering PCSK9 inhibitor alirocumab as a new treatment for proteinuric CKD and the effect of SGLT2 inhibition using empagliflozin in obese ZSF1 rats. Regarding renoprotection, our findings were contradictory with previous preclinical studies and clinical data, suggesting that different pathophysiological mechanisms may apply to this rat model.

Effect of sodium glucose cotransporter-2 inhibitors (SGLT-2is) on the clinical outcomes of patients with diabetic atrial fibrillation

BackgroundDiabetes mellitus (DM) and atrial Fibrillation (AF) are among the most common health issues. They are responsible for the highest rates of morbidity and mortality. The importance of sodium glucose cotransporter-2 inhibitors (SGLT-2is) in treating DM has increased significantly in recent years. In our article, we aimed to evaluate the effect of SGLT-2i on the clinical outcomes of AF patients with DM.MethodsOur study is a retrospective, observational study. The patients with AF and DM were divided into two groups: those using SGLT-2i or not using SGLT-2i, and 3-year follow-up results were examined. The endpoints of the study were defined as all-cause death, the development of myocardial infarction (MI), major bleeding requiring hospitalization, and an ischemic cerebrovascular event (CVE). Differences between groups according to SGLT-2i use were analyzed.ResultsThe study included 485 patients, 205 (42.3%) of whom were male and had an average age of 70.7 ± 9.7 years. A total of 138 of 485 patients (28.5%) received SGLT-2i. All-cause mortality was lower in the group receiving SGLT-2i (p < 0.001). Similarly, a significant reduction in major bleeding events was observed among those who received SGLT-2i treatment (p = 0.009). The incidence of CVEs was lower among SGLT-2i recipients, but the difference was not statistically significant (p = 0.066). SGLT2i usage did not mitigate the risk of MI development (p = 0.317).ConclusionsIn our study, SGLT-2i treatment was associated with a significant reduction in all-cause mortality and major bleeding in diabetic AF patients. Our study provides evidence of the clinical benefit of SGLT-2i in AF patients.

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Body Composition and Fluid Status in Cardiovascular Rehabilitation Patients with Coronary Artery Disease and Heart Failure.

Background and Objectives: Sodium glucose cotransporter-2 (SGLT-2) inhibitors have emerged as integral therapeutic tools in the management of patients with cardiovascular-kidney-metabolic (CKM) syndrome. In addition to their well-documented effects on lowering glucose levels and cardiovascular- and reno-protective actions, SGLT-2 inhibitors, through a reduction in body weight (BW), generate changes in the body composition and volume status that have not been clearly studied. Materials and Methods: This retrospective, observational longitudinal cohort, single-center study analyzed and compared body composition and fluid status measured by bioelectrical impedance analysis (BIA) from weeks 0 to 12 after the initiation of the cardiac rehabilitation (CR) program for coronary artery disease and heart failure in 59 patients who started treatment with SGLT-2 inhibitors (SGLT-2iG) and 112 patients without SGLT-2 inhibitors (non-SGLT-2iG). Results: Changes between the baseline and week 12 in the SGLT-2iG and non-SGLT-2iG were -0.3 L (p = 0.003) and -0.03 L (p = 0.82) in extracellular water (ECW) (p = 0.05), -0.39 L (p < 0.001) and -0.14 L (p = 0.33) in intracellular water (ICW) (p = 0.12), -0.69 (p < 0.001) and -0.16 (p = 0.52) in total body water (TBW) (p = 0.08), and -0.01 (p = 0.37) and -0.001 (p = 0.25) in the ECW/TBW ratio, respectively. After 3 months of exercise therapy in the CR program, patients in the SGLT-2iG showed a greater decrease than the non-SGLT-2iG in weight (-1.34 kg, p < 0.001 vs. -0.99, p = 0.02), body mass index (BMI) (-0.45 kg/m2, p < 0.001 vs. -0.38, p = 0.004), arm circumference (-0.57 cm, p = 0.008 vs. -0.12 cm, p = 0.21), waist circumference (-1.5 cm, p = 0.04 vs. -0.11 cm, p = 0.83), systolic blood pressure (SBP) (-8.9 mmHg, p = 0.049 vs. -4.19, p = 0.08), and diastolic blood pressure (DBP) (-5.15, p = 0.03 vs. -2.85, p = 0.01). The bioelectrical impedance analysis (BIA) revealed a significant decrease in body fat mass (BFM) and visceral fat area, without a loss of lean body mass (LBM) or skeletal muscle mass in the SGLT-2iG. Conclusions: SGLT-2 inhibitors exert beneficial effects on body compartments and volume status. Although they induce modest weight loss, this appears to be mainly directed at ECW, BFM, and visceral fat, without a loss of LBM nor skeletal muscle mass, which could contribute to the observed CKM benefits.

Effects of sodium-glucose cotransporter-2 inhibitors in myocardial infarction patients: A systematic review and meta-analysis.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to improve cardiovascular outcomes in individuals with heart failure (HF), type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, their efficacy following myocardial infarction (MI) remains unclear. A systematic search was conducted using PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov. Primary outcomes included hospitalization for heart failure (HHF), cardiovascular (CV) death, a composite of HHF or CV death, all-cause death, major cardiovascular events (MACE), recurrent MI, severe arrhythmia, renal injury and stroke. Secondary outcomes targeted improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV). Thirteen studies comprising 22 370 patients were included. Meta-analysis revealed that SGLT2 inhibitors reduced HHF (RR 0.69, 95% CI 0.61 to 0.78, p < 0.001), combined HHF or CV death (RR 0.87, 95% CI 0.77 to 0.99, p = 0.028), all-cause mortality (RR 0.82, 95% CI 0.73 to 0.93, p = 0.002), MACE (RR 0.68, 95% CI 0.53 to 0.88, p = 0.004), recurrent MI (RR 0.81, 95% CI 0.69 to 0.94, p = 0.007), severe arrhythmia (RR 0.54, 95% CI 0.34 to 0.85, p = 0.009) and renal injury (RR 0.68, 95% CI 0.53 to 0.87, p = 0.002). Improvement in LVEF (MD 3.96%, 95% CI 2.52 to 5.40; p < 0.001) and LVEDV (MD -5.52 mL, 95% CI -10.21 to -0.83; p = 0.021) was notably greater in the SGLT2 inhibitors group. In post-MI patients, we first found that SGLT2 inhibitors significantly lowered the risk of HHF, combined CV death or HHF, all-cause death, MACE, recurrent MI, severe arrhythmias and renal injury. Additionally, SGLT2 inhibitors improved LVEF and LVEDV.

Beyond ketosis: the search for the mechanism underlying SGLT2-inhibitor benefit continues.

Despite the impressive clinical benefits and widespread adoption of sodium glucose cotransporter 2 inhibitors (SGLT2i) to treat all classes of heart failure, their cardiovascular mechanisms of action are poorly understood. Proposed mechanisms range broadly and include enhanced ketogenesis, where the mild ketosis associated with SGLT2i use is presumed to be beneficial. However, in this issue of the JCI, carefully conducted metabolic flux studies by Goedeke et al. comparing the effects of SGLT2i and exogenous ketones suggest differential effects. Thus, the mechanisms of action for SGLT2i are likely pleiotropic, and further work is needed to fully understand their beneficial effects.

Unveiling the podocyte-protective effect of sodium-glucose cotransporter-2 inhibitors.

The renoprotective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in both diabetic and nondiabetic nephropathy are widely recognized due to results from randomized controlled trials notably the DAPA-CKD and EMPA-KIDNEY trials. Research exploring the mechanisms of renoprotection indicates that SGLT2 inhibitors exert protective effects on podocytes by enhancing autophagy and stabilizing the structure of podocytes and basement membranes. Furthermore, reductions in lipotoxicity, oxidative stress, and inflammation have been confirmed with SGLT2 inhibitor treatment. Recent clinical studies have also begun to explore the effects of SGLT2 inhibitors on nondiabetic podocytopathies, such as focal segmental glomerulosclerosis. In this review, we summarize clinical and laboratory studies that focus on the podocyte-protective effects of SGLT2 inhibitors, exploring the potential for broader applications of this novel therapeutic agent in kidney disease.

Effect of SGLT-2 Inhibitor on Indices of Atrial Myopathy in Chronic Rheumatic Mitral Valve Disease

Effect of SGLT-2 Inhibitor on Indices of Atrial Myopathy in Chronic Rheumatic Mitral Valve Disease

Effect of SGLT2 inhibitors on kidney function of type 2 diabetes patients during Ramadan: A systematic review.

SGLT2 inhibitors are known for their osmotic diuretic effect, and their use by Muslim patients with type 2 diabetes during the fasting month of Ramadan may pose an increased risk of volume depletion, potentially impacting renal function. We conducted a systematic review registered on PROSPERO (registration number CRD42020204582) of studies published between 2013 and January 2023, sourced from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The study selection criteria included controlled studies that reported the use of SGLT2 inhibitors (SGLT2i) by fasting adult type 2 diabetes patients and provided data on creatinine or estimated glomerular filtration rate (eGFR) as outcomes. Two prospective observational studies, encompassing a total of 359 participants, of which 197 utilized SGLT2 inhibitors, were identified. Our findings indicated that the use of SGLT2 inhibitors during Ramadan did not result in a significant alteration in eGFR. In one study by Hassanein et al., the mean changes in eGFR for the SGLT2i group, as compared to the non-SGLT2i group, were -1.2 ± 19.4 and 3.1 ± 14.8, respectively (p = 0.06). In a study by Shao et al., the least squares mean changes for eGFR in the SGLT2i group, compared to the non-SGLT2i group, were -6.0 ± 1.5 (95% CI, -8.9 to -3.1) and -4.2 ± 1.6 (95% CI, -7.3 to -1.1), respectively (p = 0.39). Despite the limited number of observational studies available, our analysis suggests that the use of SGLT2 inhibitors by type 2 diabetes patients during Ramadan does not appear to significantly impact kidney function.

Effects of sodium-glucose cotransporter-2 inhibitors on chronic kidney disease progression: a multi-state survival model

BackgroundCurrent guidelines recommend good glycemic control in patients with type 2 diabetes (T2D) to limit the progression of associated complications with combination therapies. This study aimed to compare the rate of chronic kidney disease (CKD) progression between patients who did or did not receive sodium-glucose cotransporter-2 inhibitors (SGLT2i) using a multistate model with two intermediate states (i.e., CKD stage 4 (CKD4) and 5 (CKD5)) and one absorbing state (i.e., death).MethodsData from patients with T2D and CKD stage 3 (CKD3) were retrieved for analysis. Patients treated with SGLT2i were matched 1:2 by prescription date with non-SGLT2i patients. The multistate model was constructed from Cox survival regression models specific to each transition stage. Cumulative failure and transition probabilities were estimated from bootstrapping.ResultsData from 6582 patients (2194 and 4388 patients in the SGLT2i and non-SGLT2i groups, respectively) were analyzed. At 10-year follow-up, patients in the SGLT2i group were more likely to remain at CKD3 compared to the non-SGLT2i group: 82.3% (95% CI 79.9%, 84.6%) vs 60.4% (57.6%, 63.4%). Transition probabilities to CKD4, CKD5, and death were lower in the SGLT2i group than non-SGLT2i group: 11.3% (9.5%, 13.3%) vs 19.8% (17.4%, 22.2%), 2.4% (1.5%, 3.4%) vs 7.4% (5.8%, 9.0%), and 4.1% (2.9%, 5.3%) vs 12.4% (10.3%, 14.6%), respectively.ConclusionSGLT2i may delay the decline in renal function and slow CKD progression compared to standard care without SGLT2i.

Sodium-glucose co-transporter 2 inhibitors and new-onset diabetes in cardiovascular or kidney disease.

Individuals with heart failure (HF), other forms of cardiovascular disease, or kidney disease are at increased risk for the development and adverse health effects of diabetes. As such, prevention or delay of diabetes is an important treatment priority in these groups. The aim of this meta-analysis was to determine the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on incident diabetes in HF across the spectrum of left ventricular ejection fraction (LVEF) and across the broader spectrum of cardiovascular or kidney disease. First, the effects of dapagliflozin vs. placebo on new-onset diabetes were assessed in a pooled, participant-level analysis of the DAPA-HF and DELIVER trials. New-onset diabetes was defined as the new initiation of glucose-lowering therapy during follow-up, and time from randomization to new-onset diabetes was evaluated using Cox proportional hazards models. Second, PubMed and Embase were searched to identify large-scale randomized clinical outcomes trials (RCTs) comparing SGLT2i with placebo among adults with cardiovascular or kidney disease. A trial-level meta-analysis was then conducted to summarize the treatment effects of SGLT2i on the incidence of new-onset diabetes. In the pooled analysis of DAPA-HF and DELIVER including 5623 participants with HF but without diabetes at baseline, dapagliflozin reduced the incidence of new-onset diabetes by 33% [hazard ratio (HR), 0.67; 95% confidence interval (CI), .49-.91; P = .012] when compared with placebo. There was no evidence of heterogeneity across the spectrum of continuous LVEF or key subgroups. Among seven complementary RCTs including 17 855 participants with cardiovascular or kidney disease, SGLT2i reduced the of new-onset diabetes by 26% (HR, 0.74; 95% CI .65-.85; P < .001), with consistent effects across trials. SGLT2i reduced the incidence of new-onset diabetes among individuals with cardiovascular or kidney disease. These findings suggest that SGLT2i implementation may have an important ancillary benefit on prevention or delay of diabetes in these high-risk populations.

Potential of Sodium-Glucose Cotransporter-2 Inhibitors in the Management of Heart Failure With Preserved Ejection Fraction: A Narrative Review.

Heart failure with preserved ejection fraction presents a major clinical challenge due to its complex pathophysiology and limitations in its therapeutic options. This comprehensive review explores the comparative effectiveness of sodium-glucose cotransporter-2 inhibitors, focusing on their impact on diabetic versus non-diabetic patients, individuals with chronic kidney disease, and the elderly. A comprehensive literature search identified randomized controlled trials, meta-analyses, and clinical studies that evaluated the role of sodium-glucose cotransporter-2 inhibitors in managing heart failure with preserved ejection fraction. Findings indicate that sodium-glucose cotransporter-2 inhibitors significantly reduce heart failure hospitalizations and cardiovascular mortality. Among chronic kidney disease patients with heart failure with preserved ejection fraction, sodium-glucose cotransporter-2 inhibitors showed a decrease in the risk of cardiovascular mortality and hospitalization. Furthermore, their use in elderly patients was associated with improved health-related quality of life and cognitive function, with no notable increase in adverse events. Clinical guidelines increasingly recommend sodium-glucose cotransporter-2 inhibitors as part of heart failure with preserved ejection fraction management. However, further research is required to refine patient-specific strategies and explore additional benefits, such as their cardioprotective role post-myocardial infarction. This review highlights the effectiveness of sodium-glucose cotransporter-2 inhibitors in managing heart failure with preserved ejection fraction across various subgroups. Additionally, integrating these agents into clinical practice has significant potential to improve patient outcomes.

Nephroprotective effect of SGLT2 inhibitors in elderly patients with type 2 diabetes mellitus and hypertension: a real-world population-based cohort study

ABSTRACT Objectives This study aimed to investigate the nephroprotective effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in elderly patients with type 2 diabetes mellitus (T2DM) and hypertension based on real-world clinical data. The study aimed to provide a theoretical basis for evidence-based pharmacological treatment of chronic kidney disease in this population. Methods The ‘Health Cloud’ platform of the Shanghai Municipal Health Commission was employed to identify and screen elderly patients with T2DM and hypertension. The propensity score matching cohort was further constructed to estimate the effect of SGLT2i on the risk of rapid decline in renal function (∆eGFR≤-5 mL/min/1.73 m2 or ∆eGFR%≤-5%). Multiple sensitivity analyses were conducted to assess the robustness of the results. Results After propensity score matching, no significant differences of covariates were identified between the SGLT2i and non-SGLT2i groups. The results of multivariate logistic models demonstrated a consistent and inverse correlation between SGLT2i use and the risk of rapid eGFR decline, whether defined as ∆eGFR≤-5 mL/min/1.73 m2 (OR = 0.60, 95% CI:0.38-0.96) or ∆eGFR%≤-5% (OR = 0.57, 95% CI:0.37-0.89). In the stratification of renin-angiotensin system inhibitor (RASi) treatment, SGLT2i was associated with a lower risk of rapid eGFR decline in the RASi group (all ORs < 1, p < 0.05), with no interaction between SGLT2i and RASi (all P for interaction > 0.05) detected. Conclusions SGLT2i significantly reduced the risk of rapid eGFR decline in elderly patients with T2DM and hypertension, but the synergistic effect with RASi remains unclear.

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.

Effects of sodium-glucose cotransporter-2 inhibitor on atrial high-rate episodes in patients with cardiovascular implantable electronic device: a randomized controlled trial

Prior research has demonstrated an association between sodium-glucose cotransporter 2 (SGLT2) inhibitor and a reduced incidence of atrial fibrillation (AF). Given the established link between mitochondrial dysfunction and AF, this study aimed to explore the impact of SGLT2 inhibitors on AF burden and plausible antiarrhythmic mechanisms in patients with cardiovascular implantable electronic devices (CIEDs). Patients with atrial high-rate episodes (AHREs) detected by CIEDs were randomized to receive either 10 mg of dapagliflozin or a placebo for 3 months. AF burdens were quantified via CIEDs interrogations as AHREs duration, percentage, and number of episodes at baseline and after 3 months of treatment. Mitochondrial parameters, cellular oxidative stress, and norepinephrine levels were measured in peripheral blood mononuclear cells (PBMCs). A total of 54 patients with CIEDs were enrolled in the study. Among them, 36 patients (66.7%) had a history of clinical AF, and 9 patients (16.7%) had diabetes mellitus. After 3 months of the assigned treatment, the median longest AHRE duration decreased similarly in both the dapagliflozin and placebo groups (-77.0 vs. -162.0 min, p = 0.442). Clinical AF, as opposed to subclinical AF, was independently linked to decreased basal respiration and adenosine triphosphate (ATP) production. Although the changes in AHREs burden over the 3 months did not significantly differ between the dapagliflozin and placebo groups, dapagliflozin significantly decreased the number of AHREs per month by 2.2 episodes among patients with clinical AF, whereas the placebo group experienced an increase of 0.6 episodes (p = 0.048). Additionally, dapagliflozin significantly reduced cellular oxidative stress (from 26840 to 18164 arbitrary units, p = 0.049) and improved mitochondrial spare respiratory capacity (SRC) percentage (from 166 to 202%, p = 0.016) in patients with clinical AF. Dapagliflozin did not significantly reduce the longest AHRE duration in patients with CIED. However, in the subgroup of patients with clinical AF, dapagliflozin reduced the number of AHREs potentially via reduction of cellular oxidative stress and enhancement of mitochondrial function.The study protocol was registered at the Thai Clinical Trials Registry (TCTR identification number TCTR20210315003) on March 15, 2021.

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.

Sodium-Glucose Cotransporter 2 Inhibitors Improve Body Composition by Increasing the Skeletal Muscle Mass/Fat Mass Ratio in Patients with Type 2 Diabetes: A 52-Week Prospective Real-Life Study.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) induce body weight loss, but their effect on skeletal muscle mass (SMM) and strength needs to be better elucidated. This study aimed to evaluate the effects of SGLT2i on SMM in a real-life population setting of patients with type 2 diabetes (T2D). Secondary outcomes included changes in liver steatosis and in anthropometric and glucometabolic parameters. Seventy-one patients were treated with SGLT2is as an add-on to metformin for 52 consecutive weeks. Visits were scheduled at baseline (T0) and after 6 (T6) and 12 months of therapy (T12) and included the checking of laboratory tests, measurement of anthropometric parameters, bioimpedance analysis of body composition, and abdominal ultrasound (US). Fat mass (FM) and visceral adipose tissue (VAT) progressively decreased compared to the baseline (FM: -2.9 ± 0.6 kg at T6; -2.8 ± 0.6 kg at T12; VAT: -0.3 ± 0.1 L at T6; -0.4 ± 0.1 L at T12; all p < 0.01). Changes in SMM were less pronounced (-0.4 ± 0.3 kg at T6, ns; -0.7 ± 0.4 kg at T12, p < 0.05), yielding a beneficial increase in the SMM/FM ratio (+0.3 ± 0.05 at T6 and +0.2 ± 0.05 at T12, all p < 0.01). No significant changes in sarcopenia, sarcopenic obesity, fat-free mass, muscle strength, and water compartments were observed at the end of the follow-up period. Anthropometric and glucometabolic parameters, insulin resistance, liver enzymes, and biometric indices and US grading of hepatic steatosis improved throughout this study. In a real-life setting, SGLT2i therapy is associated with weight loss attributable to FM rather than SMM loss without any relevant deterioration in muscle strength. In addition, SGLT2is proved to have beneficial effects on steatotic liver disease.

Populationwide Screening for Chronic Kidney Disease

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have changed clinical management of chronic kidney disease (CKD) and made populationwide screening for CKD a viable strategy. Optimal age of screening initiation has yet to be evaluated. To compare the clinical benefits, costs, and cost-effectiveness of population-wide CKD screening at different initiation ages and screening frequencies. This cost-effectiveness study used a previously published decision-analytic Markov cohort model that simulated progression of CKD among US adults from age 35 years and older and was calibrated to population-level data from the National Health and Nutrition Examination Survey (NHANES). Effectiveness of SGLT2 inhibitors was derived from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial. Mortality, quality-of-life weights, and cost estimates were obtained from published cohort studies, randomized clinical trials, and US Centers for Medicare & Medicaid Services data. Analyses were performed from June 2023 through September 2024. One-time or periodic (every 10 or 5 years) screening for albuminuria, initiated at ages between 35 and 75 years, with and without addition of SGLT2 inhibitors to conventional CKD therapy (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers). Cumulative incidence of kidney failure requiring kidney replacement therapy (KRT); life years, quality-adjusted life years (QALYs), lifetime health care costs (2024 US currency), and incremental cost-effectiveness ratios discounted at 3% annually. For those aged 35 years, starting screening at age 55 years, and continuing every 5 years through age 75 years, combined with SGLT2 inhibitors, decreased the cumulative incidence of kidney failure requiring KRT from 2.4% to 1.9%, increased life expectancy by 0.13 years, and cost $128 400 per QALY gained. Although initiation of screening every 5 years at age 35 or 45 years yielded greater gains in population-wide health benefits, these strategies cost more than $200 000 per additional QALY gained. The comparative values of starting screening at different ages were sensitive to the cost and effectiveness of SGLT2 inhibitors; if SGLT2 inhibitor prices drop due to patent expirations, screening at age 55 years continued to be cost-effective even if SGLT2 inhibitor effectiveness were 30% lower than in the base case. This study found that, based on conventional benchmarks for cost-effectiveness in medicine, initiating population-wide CKD screening with SGLT2 inhibitors at age 55 years would be cost-effective.

Effect of SGLT2 Inhibitors on Erythrocytosis and Arterial Thrombosis Risk in Patients with Type 2 Diabetes Mellitus: A Real-World Multi-Center Cohort Study across the United States

Effect of SGLT2 Inhibitors on Erythrocytosis and Arterial Thrombosis Risk in Patients with Type 2 Diabetes Mellitus: A Real-World Multi-Center Cohort Study across the United States

Sodium-glucose cotransporter 2 inhibitors and glaucoma in patients with type 2 diabetes

Purpose: Pleiotropic cardiovascular benefits of sodium glucose co-transporter 2 inhibitors (SGLT2i) have been demonstrated in patients with type 2 diabetes mellitus due to vascular remodeling effects. It is unclear whether a similar benefit may be seen for glaucoma. The purpose of this study is to assess the effect of SGLT2i on the risk of glaucoma in patients with type 2 diabetes. DesignTarget trial emulation using a population-based, propensity score-matched clinical cohort approach. MethodsSetting: Population-based, propensity score-matched clinical cohort study. Study Population: Adults with type 2 diabetes in the United States who newly initiated treatment with SGLT2i, dipeptidyl peptidase 4 inhibitors (DPP4i), or glucagon-like peptide-1 receptor agonists (GLP1RA) between 2013 and 2023. After propensity score matching, 722,446 patients were included in the SGLT2i arm and the DPP4i arm, respectively. Participants were matched based on age at index, race and sex, comorbidities, and concomitant use of medications. ExposureTreatment with SGLT2i for type 2 diabetes. Main Outcome Measure(s)Incidence of new-onset glaucoma and its subtypes after initiation of SGLT2i, DPP4i, or GLP1RA. Subgroup analyses were performed to demonstrate the effect of individual SGLT2i on incident glaucoma. ResultsPatients on SGLT2i compared to those on DPP4 had a lower risk of glaucoma (HR: 0.815, 95% confidence interval [CI]: 0.794, 0.837), including open-angle glaucoma (HR: 0.755, 95%CI: 0.729, 0.781) and primary angle-closure glaucoma (HR: 0.592, 95%CI: 0.540, 0.650). Among all SGLT2i, ertugliflozin (HR: 0.668, 95%CI: 0.512, 0.871) was associated with the lowest risk of glaucoma, followed by empagliflozin (HR: 0.727, 95%CI: 0.696, 0.759), then dapagliflozin (HR: 0.814, 95%CI: 0.774, 0.855). The protective effect of SGLT2i on glaucoma was validated when compared with GLP1RA (HR: 0.932, 95%CI: 0.906, 0.959). Conclusions: Patients on SGLT2i, especially ertugliflozin and empagliflozin, had a significantly lower risk of incident glaucoma compared to those on DPP4i, an association that was less robust but significant in a sensitivity analysis using GLP1RA as the active comparator. SGLT2i had a protective effect for both open-angle glaucoma and angle-closure glaucoma.