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Identifying Barriers To SGLT2 Inhibitor Use In Eligible Patients With Heart Failure: A Real-world Experience From A Single Centre

Introduction Sodium-glucose cotransporter-2 inhibitor (SGLT2-i) have been shown to reduce risks of clinical events in patients with heart failure (HF). However, data on the use of SGLT2-i in patients with left ventricular assist devices (LVAD) are scarce. We thought to assess the efficacy and safety of SGLT2-i in patients with LVAD Methods A systematic search was done in PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to December 2023. We used all relevant words for "SGLT2-i" and "LVAD" to search in databases and we included studies and published abstracts in peer-reviewed journals of studies assessed SGLT2-i in patients with LVAD. The efficacy and safety data were extracted across the studies. RevMan 5.4.1 was used for meta-analysis. Results Three studies and eight abstracts totaling 209 patients using SGLT2-i were included. Empagliflozin, Dapagliflozin, and Canagliflozin were the used SGLT2-i across the included studies. SGLT2-i effectively decreased hemoglobin A1c (HbA1c) (Mean = -0.44, 95% CI [-0.79, -0.09], p = 0.01) and diuretic dose (Mean=-2.54, 95% CI [-3.56, 1.51], p< 0.00001) from baseline. No significant improvement was found for glomerular filtration rate (GFR), B-type natriuretic peptide (BNP), or mean pulmonary artery pressure (MPAP). Regarding safety, the pooled percentage of people with driveline infection was 9.33%, 95% CI [2.05, 16.60], p=0.01. Conclusion SGLT2-i effectively improves HbA1c and diuretic dose in patients using LVAD. Further randomized studies with a large number of participants may be warranted.

Use of Sodium-Glucose Cotransporter-2 Inhibitors in Renal Transplant Patients With Diabetes: A Brief Review of the Current Literature

To provide clinical guidance and an overview of the available data on the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure with reduced ejection fraction (HFrEF), regardless of the presence of type 2 diabetes mellitus (T2DM). We searched the MEDLINE database via PubMed (from January 2015 to November 2020) for the following key terms: SGLT2 inhibitors, sodium-glucose co-transporter-2 inhibitors, SGLT2i, heart failure, and heart failure with reduced ejection fraction. To be included in the review, the articles needed to assess the effects of SGLT2 inhibitors in the heart failure (HF) scenario. There is consistent evidence that SGLT2 inhibitors reduce the risk of major adverse cardiovascular (CV) events and hospitalization in patients with HFrEF, even in the absence of T2DM. On May 5, 2020, the U.S. Food and Drug Administration approved dapagliflozin for adults with HFrEF, regardless of the presence of T2DM, even in those patients on standard therapy, including an angiotensin receptor/neprilysin inhibitor. The SGLT2 inhibitors are well tolerated, and their once-daily dosing without the need for adjustments is convenient. These drugs can be considered a major breakthrough in pharmacotherapy for HF, providing physicians with a new treatment approach to reduce major clinical outcomes. SGLT2 inhibitor therapy reduces CV death and hospitalizations in HFrEF patients regardless of T2DM. The decision to prescribe this class of drugs should not be determined by glycemic status.

Obstructive sleep apnea (OSA) is characterized by hypoxic episodes due to collapse of the airway during sleep and is frequently associated with obesity, type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). There is currently no pharmacological agent approved for the treatment of OSA. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have the potential to both increase life expectancy and quality of life of these patients making them promising agents for this role. There are relatively few studies investigating this possible beneficial relationship between these drugs and OSA. We aimed to increase awareness on the potential benefits of SGLT2 inhibitors in OSA patients by describing the current evidence on the effectiveness of these inhibitors in both overall and cardiovascular morbidity and mortality. We performed a literature search for articles reporting on the use of SGLT2 inhibitors in patients with OSA and T2DM. We identified 4 manuscripts studying the use of SGLT2 inhibitors in 475 OSA patients with T2DM. Among them, 332 patients were administered SGLT2 inhibitors, and 143 patients were in a control group. SGLT2 inhibitors have many potential positive impacts on OSA patients by targeting various mechanisms involved in OSA pathogenesis. SGLT2 inhibitors are prime pharmacological candidates for the treatment of OSA, and additional studies are needed to better explore mechanisms and outcomes unique to this population. Additionally, patients with OSA often have multiple comorbidities that are clinical indications for SGLT2 inhibitor therapy. Physicians should recognize and encourage the use of these agents in such patients.

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have proven to be effective in improving glycemic control in patients with type 2 diabetes mellitus (T2DM). However, the risk of diabetic ketoacidosis (DKA) in patients remains unclear. The purpose of this study is to conduct this systematic review and network meta-analysis for the risk of DKA of SGLT2 inhibitors in patients with T2DM. Methods: We searched for randomized controlled trials (RCTs) concerning SGLT2 inhibitors in patients with T2DM in PubMed, EMBASE (Ovid SP), Cochrane Central Register of Controlled Trials (Ovid SP), and ClinicalTrials.gov from inception to January 2022. The primary outcomes were the risk of DKA. We assessed the sparse network with a fixed-effect model and consistency model in a frequentist framework with a graph-theoretical method by the netmeta package in R. We assessed the evidence quality of evidence of outcomes according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: In total, 36 studies involving 52,264 patients were included. The network showed that there was no significant difference observed among SGLT2 inhibitors, other active antidiabetic drugs, and placebo in the risk of DKA. There was no significant difference in the DKA risk between different doses of SGLT2 inhibitors. The certainty of the evidence ranged from very low to moderate. The probabilities of rankings and P-score showed that compared to placebo, SGLT2 inhibitors might increase the risk of DKA (P-score = 0.5298). Canagliflozin might have a higher DKA risk than other SGLT2 inhibitors (P-score = 0.7388). Conclusion: Neither SGLT2 inhibitors nor other active antidiabetic drugs were associated with an increased risk of DKA compared to placebo, and the risk of DKA with SGLT2 inhibitors was not found to be dose-dependent. In addition, the use of canagliflozin was less advisable than other SGLT2 inhibitors according to the rankings and P-score. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO, CRD42021297081.

Objective: To evaluate the frequency of non-adherence to sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with ischemic heart disease (IHD) and identify factors contributing to non-adherence at National Institute of Cardiovascular Diseases Karachi, Pakistan. Methodology: A prospective descriptive study was conducted on 171 IHD patients prescribed SGLT-2 inhibitors at the National Institute of Cardiovascular Diseases, Karachi. Adherence was assessed using the MMAS-8© scoring system, categorizing patients into high adherence (score = 8), medium adherence (score 6–7), and low-adherence (score < 6), we will take a score of <6 as Non-adherence. Factors influencing adherence, including patient education about SGLT2 inhibitors, side effects, and cost, were analyzed. Statistical analysis was performed using chi-square tests with a significance level of P ≤ 0.05. Results: Among 171 patients, 58 (33.91%) demonstrated high adherence, 42 (24.56%) had medium adherence, and 71 (41.53%) were non-adherent (P = 0.003). The primary factors influencing non-adherence included lack of patient education (24 patients, 14.03%, P = 0.001), side effects (19 patients, 11.11%, P = 0.001), and cost barriers (15 patients, 8.77%, P = 0.001). Dizziness was the most frequently reported side effect (12 patients, 63.16%). Conclusion: The study highlights significant non-adherence to SGLT-2 inhibitors, driven by education gaps, side effects, and cost issues. Addressing these factors through patient education about SGLT2 inhibitors, affordable access programs, and proactive side effect management can enhance adherence and improve cardiovascular outcomes in IHD patients.

ObjectivesTo assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes.MethodsWe searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to 17...

IDENTIFYING BARRIERS TO SGLT2 INHIBITOR USE IN ELIGIBLE PATIENTS WITH HEART FAILURE: A REAL-WORLD EXPERIENCE FROM A SINGLE CENTRE

Sodium Glucose Co-trasporter-2 Inhibitors Initiation In Patients With Advanced Heart Failure Supported With Left Ventricular Assist Device

The prevalence of obesity in Asia is of epidemic proportions, with an estimated 1 billion overweight/obese individuals in the region. The majority of patients with type 2 diabetes mellitus (T2DM) are overweight/obese, which increases the risk of cardiorenal outcomes in these patients; hence, sustained reductions in body weight and visceral adiposity are important management goals. However, most of the glucose-lowering therapies such as insulin, sulfonylureas, glinides, and thiazolidinediones induce weight gain, which makes the management of overweight/obese T2DM patients challenging. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the only oral glucose-lowering agents that have been shown to reduce body weight and visceral adiposity. In addition, SGLT-2 inhibitors therapy reduces ectopic fat deposition and improves adipose tissue function and weight-related quality of life. In this article, we aim to consolidate the existing literature on the effects of SGLT-2 inhibitors in Asian patients with T2DM and to produce clinical recommendations on their use in overweight or obese patients with T2DM. Recommendations from international and regional guidelines, as well as published data from clinical trials in Asian populations and cardiovascular outcomes trials are reviewed. Based on the available data, SGLT-2 inhibitors represent an evidence-based therapeutic option for the management of overweight/obese patients with T2DM.

Aims/IntroductionThe risk of end‐stage kidney disease increases in proportion to the decline in the estimated glomerular filtration rate (eGFR). Although protective effects of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on the eGFR decline were shown in several large‐scale clinical trials, there are no studies investigating patients with a high risk of end‐stage kidney disease. We investigated the efficacy and safety of SGLT2i in advanced renal dysfunction patients (stage G3 or G4 of chronic kidney disease) with a rapid decline in eGFR.Materials and MethodsThis retrospective, longitudinal study enrolled patients with type 2 diabetes who were treated with SGLT2i, and whose eGFR was <60 mL/min/1.73 m2 and had declined >20% over 2 years (%ΔeGFR−2y) before initiating SGLT2i. The primary end‐point was the change in eGFR 2 years after initiation (%ΔeGFR+2y) compared with %ΔeGFR−2y.ResultsA total of 17 patients among 553 patients treated with SGLT2i for ≥2 years were included in the study. The average age, glycated hemoglobin and eGFR at SGLT2i initiation were 68.5 years, 7.3% and 38.3 mL/min/1.73 m2, respectively. %ΔeGFR+2y in patients who were treated with SGLT2i was significantly increased compared with the patients not treated with SGLT2i (2.3 and −21.7%, respectively; P < 0.0001). A multiple regression analysis showed that only the proportion of the rate of eGFR decline was the independent factor associated with improvement of %ΔeGFR+2y. There was no increase in serious adverse events including acute kidney injury.ConclusionsSGLT2i was safe, and prevented further eGFR decline in patients with type 2 diabetes and advanced renal dysfunction.

The aim of this review is to summarize existing research investigating the use of sodium glucose cotransporter-2 (SGLT2) inhibitors in patients with type 1 diabetes mellitus (T1DM) while highlighting potential strategies to mitigate the risk of diabetic ketoacidosis (DKA). SGLT2 inhibitors have been studied in patients with T1DM in phase 3 clinical trials such as the inTandem, DEPICT, and EASE trials, which demonstrated consistent reductions in HbA1c. Secondary analyses of these trials have also reported potential kidney protective effects that are independent of improved glycemic control. However, trials in patients with type 2 diabetes mellitus (T2DM) have found an increased risk of DKA with SGLT2 inhibitors, a serious concern in patients with T1DM. SGLT2 inhibitors provide cardiovascular benefits and kidney protection in patients with T2DM and are a promising therapeutic option for patients with T1DM due to overlapping pathophysiological mechanisms. However, SGLT2 inhibitors increase the risk of DKA, and there is currently a lack of research investigating the beneficial effects of SGLT2 inhibitors in patients with T1DM. Preventative measure for DKA would have to be implemented and the risks would need to be carefully balanced with the benefits offered by SGLT2 inhibitors. Additional research will also be required to determine the kidney protective effects of SGLT2 inhibitors in patients with T1DM and diabetic kidney disease and to quantify the risk of DKA after the implementation of preventative measures, proper patient education, and ketone monitoring.

Introduction: Acute heart failure (AHF) presents challenges due to its poor prognosis and limited therapeutic options compared to chronic heart failure (CHF). The potential benefits of SGLT2 inhibitors in AHF patients are being explored, yet systematic evaluation is lacking. Our meta-analysis aims to bridge this gap by comparing the efficacy and safety of SGLT2 inhibitors versus placebo in AHF patients. Research question: Clinical Outcomes Of SGLT2 Inhibitors In Patients Hospitalized With Acute Heart Failure Methods: We searched Medline, Embase, and Cochrane databases for randomized controlled trials involving adult patients hospitalized with AHF, who received SGLT2 inhibitors. Our primary outcomes were all-cause mortality, heart failure events, and readmissions. The secondary outcomes were change in KCCQ-TSS (Kansas City Cardiomyopathy Questionnaire), weight, length of stay and NT-proBNP levels. Safety outcomes included hypotension, hypoglycemia, UTI, DKA, and acute renal failure. We used Review Manager 5.4 for statistical analysis, employing standardized mean difference (SMD) and risk ratio (RR) with 95% confidence intervals (CI). Results: Seven RCTs were included, involving a total of 2321 patients, with 49.5% receiving SGLT2 inhibitors. Patients receiving SGLT2 inhibitors showed a significant reduction in the risk of readmissions by 32% (RR = 0.68, p &lt; 0.00001). They also showed a non-significant but reduced risk of all-cause mortality by 24% (RR = 0.76, p = 0.04), and heart failure events by 27% (RR = 0.63, p = 0.09). With respect to the secondary outcomes, there was a significant reduction in KCCQ-TSS (SMD= -0.17; 95% CI: -0.26 to -0.08; p=0.004) and weight (SMD= -0.34; 95% CI: -0.55 to -0.13; p=0.002) in the intervention group as compared to the placebo group. This group was also associated with a non-significant but reduced length of stay (SMD= -0.01; 95% CI: -0.20 to -0.18; p=0.90) and NT-proBNP levels (SMD= -0.06; 95% CI: -0.29 to -0.17; p=0.61). On analysis of the safety outcomes, there was a non significant difference in the risk of acute renal failure, UTI, and DKA. Conclusion: In patients with AHF, initiation of SGLT2 inhibitors showed a statistically significant reduction in heart failure rehospitalizations, improved weight-based diuretic efficiency, and KCCQ-TSS. These findings suggest that starting SGLT2 inhibitors in patients hospitalized for AHF is well tolerated and leads to clinical benefits.

Owing to the pharmacological mechanism, sodium-glucose cotransporter 2 inhibitors (SGLT2is) may be less effective in patients with reduced renal functions, but no systematic review or meta-analysis addressed chronic kidney disease (CKD) patients specifically. We aimed to assess the efficacy and safety of SGLT2is in CKD patients. We conducted a systematic review and meta-analysis of randomized controlled trials. Mean difference (MD) were pooled for the decline of glomerular filtration rate (eGFR) and change in urine albumin-to-creatinine ratio (uACR). Hazard ratio (HR) and rate ratio (RR) were pooled for composite of renal outcomes and adverse effects. Thirty articles were identified. Overall MD in rate of eGFR decline was 0.02 (P = 0.05), with a borderline significant difference favoring SGLT2is, while the change in uACR from baseline was - 141.34mg/g and hazard ratio of composite renal outcomes was 0.64 significantly favoring SGLT2is. Subgroup analyses showed that the long-term renal function, participants with baseline macroalbuminuria, and stage 4 CKD patients had significantly slower eGFR decline rate in SGLT2is compared to the placebo group. Risks of genital mycotic infection and ketoacidosis were significantly higher among the SGLT2is group than placebo. For CKD patients, no matter diabetic or non-diabetic, our study showed potential renoprotective effects favoring SGLT2is in overall and long-term phase, and in patients with macroalbuminuria or stage 4 CKD. However, only slight increased risk of adverse effects among the SGLT2is group is observed. Therefore, we concluded that in CKD patients, prescribing SGLT2is was safe and had renal benefits.