Effects Of SGLT2 Inhibitors Research Articles

Sodium-glucose cotransporter 2 inhibitors and outcomes in transthyretin amyloid cardiomyopathy: Systematic review and meta-analysis.

Transthyretin amyloid cardiomyopathy (ATTR-CM) commonly leads to heart failure but has traditionally been an exclusion criterion in randomized clinical trials (RCTs) of sodium-glucose cotransporter 2 inhibitors (SGLT2i); therefore, the effects of these drugs in this population remain undocumented. In light of recent studies, this meta-analysis aimed to investigate the effect of SGLT2i on the prognosis of patients with ATTR-CM. A comprehensive search of Medline, Scopus, and the Cochrane Library was conducted up to November 17, 2024. Study selection, data extraction and quality assessment were carried out independently by two investigators. Associations of SGLT2i with outcomes were pooled using random-effects meta-analyses. A total of five studies (9766 participants, 4 propensity score-matched) were included. The use of SGLT2i was associated with significant reductions in all-cause mortality [hazard ratio (HR) .54, 95% confidence interval (CI) .44-.66], cardiovascular mortality (HR .39, 95% CI .23-.65), major adverse cardiovascular events (HR .71, 95% CI .61-.83), and heart failure hospitalizations (HFHs) (HR .63, 95% CI .52-.77) compared to non-use. The odds of cardiac arrhythmias were significantly lower among SGLT2i users compared to non-users [odds ratio (OR) .73, 95% CI .65-.83]. Specifically, SGLT2i use was associated with significant reductions in the odds of atrial fibrillation (AF) (OR .75, 95% CI .62-.91), ventricular tachycardia (OR .72, 95% CI .59-.88), and sudden cardiac arrest (OR .71, 95% CI .50-.99). The use of SGLT2is may be associated with a more favourable prognosis in patients with ATTR-CM. Adequately powered, long-term RCTs are required to validate the available observational evidence.

Age-dependent effects of SGLT2 inhibitors on stroke risk in geriatric patients with diabetes and atrial fibrillation

BackgroundAtrial fibrillation (AF) and diabetes mellitus (DM) are associated with an increased risk of ischemic stroke, particularly in geriatric populations. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits, but their effects on stroke risk may vary by age. This study aimed to explore the age-dependent effects of SGLT2i on stroke risk in patients with AF and DM.MethodsThis historical longitudinal follow-up cohort study included 9,669 patients with AF and DM from the National Taiwan University Hospital database (2010–2020). Patients were stratified into three age groups (< 75, 75–89, and ≥ 90 years) to compare SGLT2i users and non-users within each age group. Cox proportional hazards models were used to evaluate stroke risk, adjusting for CHA₂DS₂-VASc score and oral anticoagulant use. Interaction analysis assessed age-specific SGLT2i effects.ResultsIn patients aged < 75 years, SGLT2i use significantly reduced stroke risk (HR 0.63, 95% CI 0.44–0.88, P < 0.05). Stroke risk was neutral in patients aged 75–89 years (HR 0.95, 95% CI 0.60–1.50), but significantly increased in those aged ≥ 90 years (HR 5.04, 95% CI 1.20–21.1, P < 0.05). Interaction analysis confirmed a significant age-dependent effect (aged ≥ 90 years x SGLT2i use HR 6.39, 95% CI 1.49–27.40, P < 0.05).ConclusionsThe impact of SGLT2i on stroke risk varies significantly by age. While protective in younger patients, SGLT2i may increase stroke risk in those aged ≥ 90 years. These findings highlight the importance of age-specific considerations in prescribing SGLT2i for patients with AF and DM.Graphical

Use of SGLT2i in Non-Diabetic Kidney Transplant Recipients.

The potential anti-proteinuric effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) is of special interest in kidney transplantation. Its benefits have been demonstrated in diabetic kidney transplant recipients (KTRs). We analyzed the efficacy and safety of SGLT2i in non-diabetic KTRs collecting clinical and analytical data at baseline and 6 months after the introduction of the drug. We performed a unicenter observational study including all non-diabetic KTRs who were prescribed SGLT2i as antiproteinuric therapy. We analyzed clinical and analytical data at baseline and after 6 months of starting SGLT2i. We included 22 patients (68.2% men), median age 58 years, with a median post-transplant period of 67 months. Hypertension was present in 95% of the patients, 90% had dyslipidemia, and 68.2% were receiving treatment with renin-angiotensin-aldosterone system blockade agents plus antialdosterone drugs. The most used SGLT2i was dapagliflozin (91%). The median baseline creatinine was 2.1 (1.48 to 2.85) mg/dL, estimated glomerular filtrate rate (eGFR) 31 (23.7 to 45,2) mL/min, and urinary protein/creatinine ratio 1.68 (0.58 to 2.9) g/g. After 6 months of follow-up, we found a significant reduction in proteinuria (1.68 to 1.06 g/g, P = .025), as well as a reduction in uric acid and high-density lipoprotein (HDL). There was a mild significant reduction in eGFR (31 to 28.5 mL/min, P = .001), which was greater in patients with recurrence of the underlying disease or chronic rejection. The drug was discontinued in two patients (9.1%): one due to a urinary tract infection (UTI) and another one due to hemodialysis initiation. There were no cardiovascular events or death. The use of SGLT2i in our cohort was effective to reduce proteinuria in non-diabetic KTRs after 6 months of treatment with an acceptable safety profile.

Sodium-Glucose Cotransporter 2 Inhibitors and Changes in Epicardial Adipose Tissue: A Systematic Literature Review And Meta-Analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a groundbreaking class of antidiabetic medications renowned for their glucose-lowering effects and cardiovascular benefits. Recent studies have suggested that SGLT2 inhibitors may extend their influence beyond glycemic control to impact adipose tissue physiology, particularly within the epicardial adipose depot. Epicardial adipose tissue (EAT), an actively secretory organ surrounding the heart, has been implicated in the modulation of cardiovascular risk. This systematic review and meta-analysis aims to systematically review and synthesize existing literature on the effects of SGLT2 inhibitors on EAT. We performed a literature search for studies assessing the changes in epicardial adipose tissue volume/thickness before and after treatment with an SGLT2 inhibitor. We excluded reviews, editorials, case reports/case series, experimental studies, and studies that did not use SGLT2 inhibitors as the intervention. The main outcome of interest was the change in EAT volume/thickness at follow-up. The literature search yielded 72 results. After the application of the exclusion criteria, a total of 11 studies were selected for data extraction and inclusion in the meta-analysis. A mean of 6.57ml decreased EAT volume, and EAT thickness was reduced by a mean of 1.55mm. We detected that treatment with an SGLT2 inhibitor was associated with decreased EAT volume/thickness compared to the control group (SMD -1.79, 95% CI -2.91 to -0.66, p<0.01). There was substantial betweenstudy heterogeneity (I2: 94%, p<0.001). Results remained robust even after the exclusion of any single study. Subgroup analysis revealed a significantly greater effect size in randomized studies. Funnel plot inspection and Egger's regression test did not indicate the presence of publication bias Conclusion: This meta-analysis suggests that SGLT2 inhibitors use is associated with a reduction in EAT volume/thickness, posing as a potential mechanism of their beneficial effects in heart failure outcomes.

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.

A Systematic Review and Meta-Analysis of Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitors and Their Impact on the Management of Heart Failure.

Heart failure (HF) is a life-threatening condition with severe incapacitating consequences. Many body organs and systems may be affected, which may also hinder the quality of life and finances at the individual and societal levels. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have also emerged as potentially useful drugs in the HF domain and other medical fields, in addition to their glucose-lowering effect.This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the authors searched Google Scholar, PubMed, and Scopus websites for SGLT2i and SGLT2i-related terms and their impact on HF events, major adverse cardiovascular events (MACEs), renal composite outcomes, and improvement in the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, involving human adult populations. Two reviewers conducted the literature search, and disagreements were resolved through mutual consensus and input from a third reviewer. A literature search was conducted from 1st February to 20th February 2024.We included studies published after 2018 to focus only on the latest advancements. Randomized controlled trials, observational studies, or systematic reviews of these studies were included in our study. Of the 44 initial articles identified, only 14 met the inclusion and exclusion criteria. The outcomes revealed the superiority of SGLT2i therapeutics over placebo in all four domains mentioned above. A total of 234,509 patients from 11 papers with moderate heterogeneity (P = 0.07; I2 = 42%) evaluating the effect of SGLT2i in comparison to placebo on HF events were considered; of these, 128,477 patients received the intervention drug, and 106,032 individuals were assigned to the control group. The absolute numbers of HF events were 6845 and 8877, respectively. The study showed an overall benefit of SGLT2i in patients with heart failure due to their ability to major adverse cardiovascular events (MACE) in comparison to placebo (OR: 0.92; 95% CI: 0.89-0.96; P < 0.00001). This systematic review confirmed previous findings related to the use of SGLT2i as adjunctive therapy for HF and amelioration of KCCQ scores and as a protective agent against MACE and renal impairment progression.

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.

Contemporary prospects for the use of sodium-glucose cotransporter-2 inhibitors

To determine contemporary prospects for the use of non-glycemic effects of sodium-glucose cotransporter-2 inhibitors in comorbid patients, the analysis of existing studies was carried out. The mechanisms of action of sodium-glucose cotransporter-2 inhibitors discovered during the EMPA-REG OUTCOME study which were previously unknown, encouraged further research on the use of these drugs in other pathological conditions. The authors of the article have analyzed some clinical and preclinical studies on the use of this drug group in such conditions as stroke, cancer, rheumatological diseases, and rhythm disorders, as well as their impact on the development of major adverse cardiovascular events. The effects of oxidative stress suppression in the myocardium and nervous tissue with an increase in the number of mitochondria which reduces the risk of developing rhythm disorders, improves neoangiogenesis in the focus of ischemic necrosis, and has neuroprotective effects are described in the article. In oncological diseases, gliflozins prevent proliferation of tumor cells and oncogenesis through the induction of late apoptosis and also have cardioprotective effects in patients undergoing chemotherapy. The use of these medicines reduces the incidence of major adverse cardiovascular events, as well as restenosis after intravascular interventions. The positive effect on the course of rheumatological diseases was in improving laboratory parameters in a number of diseases and reducing the frequency of exacerbations and visits to a doctor in patients with gout. With a constant increase in the number of patients with comorbid conditions, it is important to carry out further study of pleiotropic effects of sodium-glucose cotransporter-2 inhibitors for the subsequent introduction of new data into clinical practice.

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.