SGLT2 Inhibitors In Patients Research Articles

Role of SGLT-2 Inhibitors in Ultrafiltration Failure in Peritoneal Dialysis: A Narrative Review.

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are glucose lowering agents with protective effects on cardiovascular health and the ability to slow chronic kidney disease (CKD) progression. The benefits of SGLT-2 inhibitors have not been studied in patients with advanced CKD or on maintenance dialysis. Ultrafiltration failure is a common reason for failure of peritoneal dialysis (PD). Glucose transporters, such as SGLT-2, are involved in the progression to ultrafiltration failure, and hence, SGLT-2 inhibitors might be beneficial in patients on PD to prevent ultrafiltration failure. Here, we review data from animal models and ongoing clinical trials of SGLT-2 inhibitors in advanced CKD, as well as considerations for a phase III trial in patients on PD. A literature search was conducted and information on clinical trials was obtained from clinicaltrials.gov. Animal models of PD have shown upregulation of glucose transporters in the peritoneal membrane and a potential effect of SGLT-2 inhibitors on glucose absorption and ultrafiltration. Several clinical trials are currently ongoing with SGLT-2 inhibitors in patients on PD. We discuss their study designs and propose a mixed-methods, patient-centered approach to studying SGLT-2 inhibitors in PD patients. We also discuss the potential implications of SGLT-2 inhibitors on people living with kidney failure, especially in remote communities.

Efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with acute heart failure: a systematic review and meta-analysis.

The effectiveness and safety of a novel class of hypoglycemic medications known as sodium-glucose cotransporter 2 (SGLT2) inhibitors have not been completely established in relation to acute heart failure (AHF). Consequently, we sought to compare the prognostic and safety outcomes of patients administered SGLT2 inhibitors for the treatment of AHF. An extensive search of the Web of Science, PubMed, and EMBASE was conducted for randomized controlled trials and observational studies that have evaluated the use of SGLT2 inhibitors in AHF from the inception of these drugs to the present. We compiled data related to cardiovascular safety and prognosis. Aggregated risk ratios (RR), mean differences (MD), or standardized mean differences (SMD) were generated for all outcomes, with 95% confidence intervals (CIs), to evaluate the predictive significance of SGLT2 inhibitors in patients with AHF. We identified 4,053 patients from 13 studies. Patients experienced a substantial reduction in all-cause mortality (RR = 0.82, 95% CI: 0.70-0.96, P = 0.01), readmission rates (RR = 0.85, 95% CI: 0.74-0.98, P = 0.02), the number of heart failure exacerbation events (RR = 0.69, 95% CI: 0.50-0.95, P = 0.02), and the number of rehospitalization events due to heart failure (RR = 0.71, 95% CI: 0.58-0.86, P < 0.05) in the SGLT2 inhibitors-treatment group compared to a placebo or standard care (control group). SGLT2 inhibitors improved patient quality of life (SMD = -0.24, 95% CI: -0.40 to -0.09, P = 0.002). SGLT2 inhibitors were associated with enhanced diuresis in patients with AHF (MD = 2.83, 95% CI: 1.36-4.29, P < 0.05). Overall, treatment with SGLT2 inhibitors significantly reduced the level of serum NT-proBNP (MD = -497.62, 95% CI: -762.02 to -233.21, P < 0.05) and did not increase the incidence of adverse events (RR = 0.91, 95% CI: 0.82-1.01, P = 0.06). This meta-analysis suggests that treatment with SGLT2 inhibitors is associated with a better prognosis in patients with AHF than in patients not treated with SGLT2 inhibitors. It is safe and effective to initiate SGLT2 inhibitors in patients with AHF. https://www.doi.org/10.37766/inplasy2024.9.0015, identifier (INPLASY202490015).

Expanding the possibilities of using sodium-glucose cotransporter 2 inhibitors in patients with heart failure.

Aim: To study the potential mechanisms of the beneficial cardiovascular effects of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, the possibilities of improving the treatment and prognosis of patients with acute heart failure (HF) during their use. Materials and Methods: The data analysis of literary sources has been conducted regarding the results of existing studies evaluating the clinical benefit and safety of SGLT-2 inhibitors in patients with acute heart failure. Conclusions: The peculiarities of the pharmacological action of SGLT-2 inhibitors and the obtained research results expand the possibilities of using this group of drugs, demonstrating encouraging prospects in improving the prognosis of patients hospitalized with acute heart failure.

Risk of bone fracture by using dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus: a network meta-analysis of population-based cohort studies.

Type 2 diabetes mellitus (T2DM) is linked to a heightened likelihood of experiencing fractures. It is crucial to ascertain whether medications used to lower blood sugar levels can elevate the risk of fractures. We aimed to investigate and compare the effects of glucagon-like peptide 1 receptor agonists (GLP-1RA), Dipeptidyl Peptidase-4 Inhibitors (DPP-4i), and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) on the fracture risk in patients with T2D in the real world. A network meta-analysis conducted an inclusive literature search in PubMed, Scopus, Web of Science, and Cochrane Library to select appropriate population-based cohort studies that investigated the risk of bone fractures of (GLP-1RA), (DPP-4i) or (SGLT-2i) in the real world. A network meta-analysis (NMA) was performed using R software to investigate the risk of total fractures as a primary outcome among patients who used (GLP-1RAs), (SGLT-2i) or (DPP-4i) versus each other or other glucose-lowering medications (GLMs). The odds ratio (OR) and 95% confidence interval (CI) were summarized overall network and for each pairwise direct and indirect comparison. The surface under the cumulative ranking curve (SUCRA) with the P-scores was calculated for each treatment in the network meta-analysis to detect their cumulative ranking probabilities in lowering the risk of total fractures. In our NMA, we identified a set of 13 population-based cohort studies comprising a total of 1,064,952 patients. The risk of fracture was identified with the follow-up duration for each class. We found a significant decrease in the fracture risk by about 87% associated with patients who used SGLT2 inhibitors in combination with other glucose-lowering medications, followed by SGLT2 inhibitors alone by about 67%, then GLP-1 receptor agonists by about 60%, and at last DPP-4 inhibitors by about 55%. Our study's collective findings suggest a significant association of the low risk of fracture with the use of SGLT2i with other GLMs combination, SGLT2i alone, GLP-1RA, and DPP-4i, respectively. This population-based analysis offers the best available evidence and might be helpful for clinicians in the decision of the most suitable T2DM treatment strategies, especially for elderly type 2 diabetic patients, as they may be safe in terms of fracture. https://www.crd.york.ac.uk/prospero/, identifier CRD42023448720.

The lower incidence of cervical cancer in type 2 diabetes mellitus with sodium-glucose cotransporter 2 inhibitors utilization.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are medications with anti-inflammatory effects used to treat type 2 diabetes mellitus (T2DM). Cervical cancer is the most common gynecological cancer and is characterized by elevated inflammatory status. Accordingly, this study aimed to investigate the potential association between SGLT2 inhibitor use and cervical cancer development. In this retrospective cohort study, female patients with T2DM were divided into 2 groups: SGLT2 inhibitor users and a control group of non-SGLT2 inhibitor users. After propensity score matching, the SGLT2 inhibitor group and control group each had 136 212 patients. Cox proportional hazards regression was conducted to obtain the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for cervical cancer between the 2 groups. Overall, 148 and 191 cases of cervical cancer were identified in the SGLT2 inhibitor and control groups, respectively. The incidence of cervical cancer was significantly lower in the SGLT2 inhibitor group than in the control group (aHR, 0.77; 95% CI, 0.62-0.96, P = 0.0179). In a subgroup analysis stratified by type of oral medication, the effect of SGLT2 inhibitors on cervical cancer development exhibited a significant difference compared with a biguanide group (aHR, 0.77; 95% CI, 0.63-0.95) and a sulfonylurea group (aHR, 0.69; 95% CI, 0.50-0.94) groups. In conclusion, the use of SGLT2 inhibitors in patients with T2DM is associated with reduced risk of cervical cancer development.

When should we consider SGLT-2 inhibitors in patients with acute decompensated heart failure?

When should we consider SGLT-2 inhibitors in patients with acute decompensated heart failure?

Efficacy and Safety of Application of SGLT-2 Inhibitors in Patients Undergoing PCI after Acute Myocardial Infarction: A Meta Analysis

Efficacy and Safety of Application of SGLT-2 Inhibitors in Patients Undergoing PCI after Acute Myocardial Infarction: A Meta Analysis

Estimating the population-level impacts of improved uptake of SGLT2 inhibitors in patients with chronic kidney disease: a cross-sectional observational study using routinely collected Australian primary care data

Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of kidney failure and death in patients with chronic kidney disease (CKD) but are underused. We evaluated the number of patients with CKD in Australia that would be eligible for treatment and estimated the number of cardiorenal and kidney failure events that could be averted with improved uptake of SGLT2 inhibitors. This cross-sectional observational study leveraged nationally representative primary care data from 392 Australian general practices (MedicineInsight) between 1 January 2020 and 31 December 2021. We identified patients that would have met inclusion criteria of key SGLT2 inhibitor trials and applied these data to age and sex-stratified estimates of CKD prevalence for the Australian population (using national census data), estimating the number of preventable events using trial event rates. Key outcomes included cardiorenal events (CKD progression, kidney failure, or death due to cardiovascular or kidney disease) and kidney failure. In MedicineInsight, 44.2% of adults with CKD would have met CKD eligibility criteria for an SGLT2 inhibitor;baseline use was 4.1%. Applying these data to the Australian population, 230,246 patients with CKD would have been eligible for treatment with an SGLT2 inhibitor. Optimal implementation of SGLT2 inhibitors (75% uptake) could reduce cardiorenal and kidney failure events annually in Australia by 3644 (95% CI 3526-3764) and 1312 (95% CI 1242-1385), respectively. Improved uptake of SGLT2 inhibitors for patients with CKD in Australia has the potential to prevent large numbers of patients experiencing CKD progression or dying due to cardiovascular or kidney disease. Identifying strategies to increase the uptake of SGLT2 inhibitors is critical to realising the population-level benefits of this drug class. University of New South Wales Scientia Program and Boehringer IngelheimEli Lilly Alliance.

Abstract #1603090: Real World Use, Effectiveness, and Safety of SGLT2 inhibitors in Patients With Type 2 Diabetes: Experience in A Tertiary Care Hospital in Qatar

Abstract #1603090: Real World Use, Effectiveness, and Safety of SGLT2 inhibitors in Patients With Type 2 Diabetes: Experience in A Tertiary Care Hospital in Qatar

Pharmacist impact on evidence-based prescribing of diabetes medications in patients with clinical atherosclerotic cardiovascular disease.

Including pharmacists on care teams of patients with type 2 diabetes (T2D) has been shown to promote guideline-based prescribing and improve glycemic control, lowering risks of adverse cardiovascular outcomes. Evidence is lacking regarding whether including pharmacists on the care team is associated with the prescribing of GLP-1 receptor agonists (GLP-1 RA) and SGLT-2 inhibitors (SGLT-2i) recommended for use in patients with T2D and atherosclerotic cardiovascular disease (ASCVD). To assess the association between having a pharmacist on the primary care team of patients with T2D and ASCVD and being prescribed a guideline-recommended GLP-1 RA or SGLT-2i. A cross-sectional analysis of patients with T2D and ASCVD seen by primary care providers at an academic medical center between June 2019 and May 2020 was completed. Patients with prescriptions for GLP-1 RA or SGLT-2i with evidence of cardiovascular benefit were identified and compared between those with pharmacist care vs usual care using multivariable log-binominal regression analyses. Of 1,497 included patients, 1,283 (85.7%) were in the usual care group (mean age 68.9 years, hemoglobin A1c 7.6%) and 214 (14.3%) in the pharmacist care group (mean age 64.5 years, A1c 9.0%). Of the pharmacist care group, 50.5% were prescribed a GLP-1 RA or SGLT-2i with cardiovascular benefit vs 17.9% in the usual care group (P < 0.001). In multivariable analyses controlling for A1c and other potential confounders, those in the pharmacist care group were 2.15 times as likely to have been prescribed a GLP-1 RA or SGLT-2i than those in the usual care group (adjusted risk ratio 2.15, 95% CI = 1.83-2.52; P < 0.001). These data provide preliminary evidence that integrating pharmacists into patient care teams is associated with increased prescribing of guideline-recommended treatment with GLP-1 RA and SGLT-2i in patients with T2D and ASCVD, yet there is room for improvement in prescribing these agents to patients with T2D and ASCVD.

Sodium glucose co-transporter-2 (SGLT) inhibitors in patients with compensated cirrhosis and diabetes: A prospective study

Aims and objective: Diabetes in patients with cirrhosis is common. SGLT-2 inhibitors are newer class of antidiabetic drugs with pleiotropic effects. Its safety and efficacy has not been evaluated in patients with advanced cirrhosis and diabetes. We evaluated safety and efficacy of SGLT-2 inhibitors in patients with compensated cirrhosis and diabetes. Material and method: Consecutive patients with compensated cirrhosis and diabetes who were started on SGLT-2 inhibitors were enrolled and followed every month for six months. Their clinical and biochemical parameters which include liver and kidney function tests, urine test, glycosylated haemoglobin (HbA1c), transient elastography (fibroscan), Mean Arterial Pressure (MAP) and change in weight since treatment initiation were noted. Any relevant side effects (urinary and genital infection, hypotension) were noted. Results: Twenty patients [(M:F: 13:7), age (55±11 yr), CTP score (6±1.3), etiology of cirrhosis (NASH related 17, HBV, n=1 and HCV, n=2), baseline MAP (91±5 mmHg)] were enrolled. Five patients had hypertension and taking angiotensin converting enzyme (ACE) inhibitors and 15 patients were also on carvidelol. Mean Fibroscan was (37±11kPa), large varices (n=3), small varices (n=16) and no varices were seen in one patient. All patients were followed up for 6 months. Patient were on dapagliflogin (n=11, 55%), empagliflogin (n=6, 30%) and remogliflogin (n=3, 15%). Twelve (60%) patients were also on metformin and 7 (35%) on Dipeptidyl peptidase 4(DPP4) inhibitors. Significant improvement was seen in total bilirubin Baseline (B), 1.19±0.5, Month 3 (Mo 3), 1.02±0.4 and Month 6 (Mo 6), 1.01±0.3 mg/dl], AST (B, 50.8±20.8, Mo 3, 49.4±20.5, Mo 6, 42.8±13.0 IU/L) and GGT (B, 63.8±24.5, Mo 3, 66.5±31.0 and Mo 6, 58.3±21.4 IU/dl) level at month 3 and 6. Glycemic index improved at month 3 and 6 and significant weight loss was seen at month 3 and 6. Serum creatinine, serum sodium level and mean arterial pressure remained unchanged at month 6. Urinary tract infection occurred in n=3 (15%), genital infection in (n=2, 10%) and compliant of frothy urine was seen in (n=4, 20%) without discontinuation of medicines.

The effect of sodium-glucose cotransporter 2 inhibitors in patients with chronic kidney disease with or without type 2 diabetes mellitus on cardiovascular and renal outcomes: A systematic review and meta-analysis.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have shown a favorable effect on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM). However, their efficacy in patients with chronic kidney disease (CKD) with or without T2DM has not yet been analyzed. To assess the cardiovascular and renal effects of SGLT-2 inhibitors in patients with CKD with and without T2DM, including all CKD patients in the current literature. We searched MEDLINE, EMBASE, CENTRAL and Scopus for randomized controlled trials of SGLT-2 inhibitors that evaluated cardiovascular and kidney outcomes in patients with CKD, or trials in which these patients were a subgroup. We defined 2 primary outcomes: a composite of cardiovascular death or hospitalization for heart failure, and a composite renal outcome. For each outcome, we obtained overall hazard ratios with 95% confidence intervals by using a random effects model. We included 14 randomized controlled trials. SGLT-2 inhibitors decreased the hazard for the primary cardiovascular outcome (HR 0.76; [95% CI 0.72-0.79]) and the primary renal outcome (HR 0.69; [95% CI 0.61-0.79]) in patients with CKD with or without T2DM. We did not find significant differences in the subgroup analyses according to diabetes status, baseline eGFR values or the type of SGLT-2 inhibitor used. In patients with CKD, treatment with SGLT-2 inhibitors in addition to standard therapy conferred protection against cardiovascular and renal outcomes. Further research on patients with non-diabetic CKD should be done to confirm the utility of these medications in this population. (PROSPERO ID: CRD42021275012).

Sodium glucose co-transporter 2 inhibitors and quality of life in patients with heart failure: a comprehensive systematic review and meta-analysis of randomized controlled trials.

Sodium glucose co-transporter 2 inhibitors (SGLT2i) are one of the cornerstones of heart failure (HF) therapy. While benefits in terms of HF hospitalizations and death are well established, their impact on quality-of-life (QoL) has not been systematically investigated. This systematic review and meta-analysis aims to evaluate the impact of SGLT2i treatment on QoL in patients with HF, by analysing data from randomized clinical trials (RCTs). We identified a total of 23 RCTs that investigated the role of SGLT2i on quality of life in patients with HF, irrespective of their left ventricular ejection fraction (LVEF). RCTs that used Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) to assess QoL and had a minimum follow-up of 3 months were included. The difference in mean change of the KCCQ-OSS between the SGLT2i group and the standard of care (SOC) group at 3 and 6 months from baseline was considered as the outcome measure. Fourteen RCTs (21737 patients) were included in the analysis. A significant improvement in KCCQ-OSS over time (p<0.001) was observed in both patients receiving SOC and those receiving SGLT2i in addition. The pooled estimate showed a significant improvement of 1.94 points [95% confidence interval (CI), 1.41-2.46] in KCCQ-OSS mean change at 3 months and of 2.18 points (95% CI, 1.13-3.24) at 6 months from baseline, with SGLT2i compared to SOC alone, irrespective of LVEF. A greater improvement in KCCQ-OSS was observed among patients with a recent episode of worsening HF compared to those with chronic stable HF. Among patients with HF, irrespective of their LVEF and clinical status, the addition of SGLT2i to SOC demonstrated a significant improvement in quality of life as early as at 3-month follow-up.

Cardiovascular outcomes and safety of SGLT2 inhibitors in chronic kidney disease patients.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors provide cardiovascular protection for patients with heart failure (HF) and type 2 diabetes mellitus (T2DM). However, there is little evidence of their application in patients with chronic kidney disease (CKD). Furthermore, there are inconsistent results from studies on their uses. Therefore, to explore the cardiovascular protective effect of SGLT2 inhibitors in the CKD patient population, we conducted a systematic review and meta-analysis to evaluate the cardiovascular effectiveness and safety of SGLT2 inhibitors in this patient population. We searched the PubMed® (National Library of Medicine, Bethesda, MD, USA) and Web of Science™ (Clarivate™, Philadelphia, PA, USA) databases for randomized controlled trials (RCTs) of SGLT2 inhibitors in CKD patients and built the database starting in January 2023. In accordance with our inclusion and exclusion criteria, the literature was screened, the quality of the literature was evaluated, and the data were extracted. RevMan 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and Stata® 17.0 (StataCorp LP, College Station, TX, USA) were used for the statistical analyses. Hazard ratios (HRs), odds ratios (ORs), and corresponding 95% confidence intervals (CIs) were used for the analysis of the outcome indicators. Thirteen RCTs were included. In CKD patients, SGLT2 inhibitors reduced the risk of cardiovascular death (CVD) or hospitalization for heart failure (HHF) by 28%, CVD by 16%. and HHF by 35%. They also reduced the risk of all-cause death by 14% without increasing the risk of serious adverse effects (SAEs) and urinary tract infections (UTIs). However, they increased the risk of reproductive tract infections (RTIs). SGLT2 inhibitors have a cardiovascular protective effect on patients with CKD, which in turn can significantly reduce the risk of CVD, HHF, and all-cause death without increasing the risk of SAEs and UTIs but increasing the risk of RTIs.

Sodium-glucose co-transporter-2 inhibitors for the prevention of atrial fibrillation: a systemic review and meta-analysis.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are reported to have cardiac benefits. The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. We aimed to investigate whether SGLT2 inhibitors can prevent AF occurrence in patients with cardiometabolic diseases. We searched MEDLINE, EMBASE, and the Cochrane CENTRAL database up to 1 July 2023. Randomized, placebo-controlled trials of SGLT2 inhibitors in patients with diabetes, heart failure, chronic kidney diseases (CKDs), or cardiometabolic risk factors were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated in the overall population and selected subgroups. Forty-six trials comprising 101 100 patients were included. Overall, no significant risk reduction of AF occurrence was observed with SGLT2 inhibitors, although there was a favourable trend (RR 0.90, 95% CI 0.80-1.01). In trials with follow-up durations of over 1 year, a similar result was achieved (RR 0.90, 95% CI 0.80-1.01). The results were consistent across different SGLT2 inhibitors, with RRs (95% CIs) of 0.82 (0.60-1.12) for canagliflozin, 0.87 (0.73-1.03) for dapagliflozin, 0.97 (0.78-1.22) for empagliflozin, 0.99 (0.66-1.50) for sotagliflozin, and 0.87 (0.58-1.29) for ertugliflozin. Analyses in different doses of SGLT2 inhibitors yielded similar results. The associations between SGLT2 inhibitors and AF occurrence were also absent in patients with diabetes, heart failure, and CKDs. For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population.

Impact of in-hospital initiation of sodium-glucose cotransporter-2 inhibitors in patients with heart failure and reduced ejection fraction

Abstract Introduction Safety and early clinical benefit make sodium-glucose cotransporter-2 inhibitor (SGLT-2i) therapy suitable for in-hospital initiation in patients with heart failure and reduced ejection fraction (HFrEF). Despite randomized controlled trials and guideline recommendations, they are underused and clinical inertia may play a role. Objectives Primary: To assess the impact of initiating SGLT-2i at discharge on 90-day prescription rates in patients with HFrEF during hospitalization for acute heart failure (AHF). Secondary: To evaluate the presence of contraindications at discharge and the independent factors associated with in-hospital prescription, and to assess clinical outcomes at 90 days. Methods Retrospective analysis of a consecutive prospective single-center cohort. Adult patients hospitalized between January 2021 and October 2022 with a primary diagnosis of AHF and left ventricular ejection fraction (LVEF) &amp;lt;40% were included. Patients who underwent heart transplantation during hospitalization, used SGLT2i before admission, died or were referred during the index hospitalization were excluded. Those who started SGLT-2i before or at discharge were compared with those who did not. The primary outcome was SGLT-2i prescription rate at 90 days, and the exploratory secondary endpoints was the composite of hospitalization or urgent visit for AHF or all-cause mortality at 90 days. Independent factors associated with inpatient SGLT-2i prescription were analyzed using a logistic regression model. Results Among 378 patients with documented HFrEF, 240 (64%) met the inclusion criteria. Mean age was 76±11 years, 75.4% were male and the mean LVEF was 25±13%. SGLT-2i was indicated during hospitalization in 31.6% of patients. A total of 86% of the cohort had a 90-day follow-up, and the SGLT2i prescription rate was 94.2% in those with in-hospital initiation and 14.4% in those without (p&amp;lt;0.001). Among those without contraindications at discharge (n=141), the independent factor associated with inpatient prescription was lower age, OR 0.96 (0.93-0.99) for each year. There were no statistically significant differences between the two groups for the combined endpoint of all-cause death, HF rehospitalisation or unplanned HF visit at 90 days (p=0.3). Conclusions In-hospital initiation of SGLT-2-i was associated with significantly higher prescription rates 90 days after discharge, without differences in death from all causes and hospitalization or urgent visit for AHF at 90 days. This study reflects the presence of medical inertia, particularly in older patients. It also highlights the hospitalization period as an optimal time to start SGLT-2i and achieve the proven clinical benefits that accumulate rapidly over weeks, with solid safety and tolerability.

Comparison of sodium-glucose cotransporter-2 (SGLT2) inhibitors to reduce cardiovascular and renal outcomes: a network meta-analysis of randomized controlled trials

Abstract Background Although the cardio- and reno-protective benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been established, the differences across agents in various populations have yet to be elucidated. Purpose To investigate the profiles of each SGLT2 inhibitor in patients from various backgrounds. Methods MEDLINE and EMBASE databases were searched in November 2022 to identify randomized controlled trials (RCTs) comparing SGLT2 inhibitor to placebo. To compare each SGLT2 inhibitor, a network meta-analysis was performed. The primary efficacy endpoint was the composite of cardiovascular (CV) mortality and hospitalisations for heart failure (HHF). The secondary efficacy endpoints were all-cause mortality, CV mortality, HHF, kidney disease progression, and acute kidney injury (AKI). We conducted subgroup analyses based on the underlying comorbidities, including diabetes and chronic kidney disease (CKD). Safety endpoints were also assessed between SGLT2 inhibitors in all cohorts. Results This study included 19 RCTs with a total of 94,495 participants, investigating empagliflozin, ertugliflozin, dapagliflozin, canagliflozin, and sotagliflozin. Although there were consistent tendencies favouring SGLT2 inhibitors over placebo, no significant difference between SGLT2 inhibitors was manifested for the primary outcome (Figures 1-2). Compared to placebo, empagliflozin and dapagliflozin improved all studied efficacy outcomes in overall population and demonstrated consistent benefits on reduction in primary outcome, HHF, kidney disease progression, and AKI independent of diabetic status. Among patients without CKD, empagliflozin were associated with lower risks of the primary outcome compared to ertugliflozin (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.60-0.98), CV mortality compared to canagliflozin (HR, 0.62; 95% CI, 0.40-0.96) and dapagliflozin (HR, 0.59; 95%CI, 0.39-0.89), and all-cause mortality compared to dapagliflozin (HR, 0.72; 95% CI, 0.52-0.99). All SGLT2 inhibitors increased the occurrence of genital infections. As compared to a placebo, canagliflozin increased the risks of limb amputation (HR, 1.58; 95% CI 1.07-2.35) and fracture (HR, 1.19; 95%CI 1.01-1.40). Conclusions SGLT2 inhibitors have comparable efficacy profiles in reducing cardiovascular and renal events. Whilst empagliflozin and dapagliflozin are beneficial even in patients without diabetes, empagliflozin may be an especially reasonable opiton in patients without CKD.Figure 1Figure 2

The effect of sodium-glucose co-transporter-2 inhibitors following anterior ST-segment elevation myocardial infarction

Abstract Background Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been clearly demonstrated to be associated with lower rate of new-onset heart failure(HF) in patients under risk of HF. In addition, due to lower rehospitalisation and better functional status in HF patients, SGLT-2 inhibitors have became the cornerstone of treatment regardless of the diabetes status. New-onset HF is very common in survivors of anterior ST-segment elevation myocardial infarction(STEMI) and requires preventive strategies, however the role of SGLT-2 inhibition in this population is not well established yet. Purpose In this study, we aimed to demonstrate the role of the SGLT-2 inhibitors in patients with anterior STEMI. Methods We prospectively enrolled patients with diabetes mellitus who had anterior STEMI, which was managed with primary percutaneous coronary intervention. Patients with previous myocardial infarction, heart failure, under SGLT-2 inhibitor treatment and chronic kidney disease were excluded. Patients were divided into two groups according to SGLT-2 inhibitor treatment; group 1 patients treated with empaglifosine or dapaglifosine and group 2 received other classes of diabetes medicine. Comorbidities regarding smoking history (p: 0.871), hypertension (p: 0.064), previous cerebrovascular accident(p: 0,348) and coronary artery disease(p: 0.201) were comparable between groups. Presence of multivessel coronary artery disease (p: 0.259) and left main coronary artery involvement (p: 0.062) were also similar between groups. Glucose level on admission was similar (p: 0.782) between groups, however HBa1C level was significantly higher in group 1(p: &amp;lt;0.001). Left ventricular ejection fraction which was calculated prior to hospital discharge was also similar between groups(p: 0.297). Mean follow-up duration was 12 months and new-onset heart failure was significantly lower in group 1 patients(p:&amp;lt;0.001). In line with the rate of new onset-heart failure, pro-BNP levels at the 12th month visit were lower in group 1 patients (p: 0.042) which was similar during the STEMI hospitalization (p: 0.668). Multivariate analyses demonstrated that the use of SGLT-2 inhibitors independently associated with lower rate of new-onset HF. Conclusion Our results indicate that SGLT-2 inhibitors decrease the rate of new-onset heart failure during the follow-up in patients with previous myocardial infarction.Baseline characteristicsUnivariate and multivariate analysis

Impact of sodium-glucose cotransporter-2 (SLGT2) inhibitors treatment initiation on the reduction of atrial and ventricular arrhythmias in patients with implanted cardiac devices

Abstract Introduction Sodium-glucose cotransporter-2 (SLGT2) inhibitors have demonstrated benefits on survival and hospital admissions in patients with heart failure and reduced ejection fraction. However, their impact on the burden of ventricular (VA) and atrial arrhythmias (AA) is unknown. Methods Retrospective multicentric study of heart failure patients with implantable cardiac defibrillator device (ICD) from 2015 to 2020 with or without cardiac resynchronization therapy (CRT) receiving SGLT2 inhibitors. Device-registered arrhythmic events were analyzed and compared during one year following SLGT2 inhibitor initiation and during one year before initiation. Relevant VA were defined as the occurrence of any sustained VT (SVT) (&amp;gt;30 seconds), ventricular fibrillation (VF), or appropriate therapy (antytachycardia pacing or shock). All VA included all the relevant VA and the occurrence of non-sustained ventricular tachycardia (NSVT). AA included atrial fibrillation (AF) burden, and episodes of more than 24 hour of AF. Results 147 patients (67 ± 10 years, 82.3% males, LVEF 30.3 ± 11%, CRT 39.3%), were included in the study. 77.6% had complete remote tele-monitoring during the entire follow up and there was no difference in the antiarrhythmic therapy between the two periods. Following SGLT2 inhibitor initiation, there was a significant reduction in the percentage of patients with relevant VA (19.7% pre vs 10.9% post; p=0.019) and all VA (47.6% pre vs 30.6% post; p&amp;lt;0.001) (Figure 1 and 2). There was a reduction in the prevalence of NSVT (40.1% pre vs. 27.2% post; p&amp;lt;0.001), of SVT (17.7% vs 8.8%; p&amp;lt;0.001), of VF (4.1% vs 2%; p=NS) and appropriate therapies (14.3% vs 9.5%; p=NS). Among patients with any VA, there was a significant reduction in the incidence of NSVT (p&amp;lt;0.001), but not in the incidence of SVT or appropriate therapies (p=NS). There was no impact on atrial fibrillation burden or in the number of AF episodes lasting more than 24 hours (p=NS). Conclusions In our study, initiation of a SGLT2 inhibitor in patients with heart failure, was associated with a reduction in the prevalence of relevant VA and any VA, with a significant reduction in the number of NSVT per patient. There was no impact on AF burden or the number of AF episodes lasting more than 24 hours. Prospective studies should be performed to sustain these conclusions.Relevant ventricular arrhythmiasAny ventricular arrhythmia

Abstract 14614: Effect of SGLT2 Inhibitors on Renal Outcomes Across Various Patient Populations

Background: The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on renal outcomes in patients with varying combinations of heart failure (HF), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) remains unclear. Methods: Online databases were queried up to May 2023 for primary and secondary analysis of trials of SGLT2i in patients with HF, CKD, or T2DM. Outcomes of interest were composite renal endpoint (defined as an eGFR &lt;15 mL/min/1.73 m2, doubling of serum creatinine, some percent change in eGFR, and/or need for kidney replacement therapy) and change in estimated glomerular filtration rate (eGFR) slope. Hazard ratios (HR) and mean difference with their 95% confidence intervals were pooled using the generic inverse variance method and a random-effects model. Results: 10 trials (n=70,117 patients) were included. Compared with placebo, SGLT2i reduced the risk of composite renal endpoint by 35% in HF (HR: 0.65; 95% CI: 0.50-0.84), 38% in CKD (HR: 0.62; 95% CI: 0.54-0.71), and 37% in DM (HR:0.63; 95% CI: 0.54, 0.73). A similar pattern of benefit was observed in different combinations of these diseases ( Figure 1 ), as well as patients without baseline HF (HR:0.57; 95% CI: 0.51, 0.63), CKD (HR:0.64; 95% CI: 0.42, 0.98) and T2DM (HR:0.62; 95% CI: 0.45, 0.86). Findings were similar for change in eGFR slope. Conclusions: SGLT2i improve renal outcomes in cohorts of HF, CKD and T2DM and these effects appear consistent across patients with different combinations of these conditions.