Outcomes in diabetic patients treated with SGLT2-Inhibitors with acute myocardial infarction undergoing PCI: The SGLT2-I AMI PROTECT Registry

Pharmacological Research, Journal Year: 2022, Volume and Issue: 187, P. 106597 - 106597

Published: Dec. 5, 2022

To investigate in-hospital and long-term prognosis in T2DM patients presenting with acute myocardial infarction (AMI) treated SGLT2-I versus other oral anti-diabetic agents (non-SGLT2-I users).

Language: Английский

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Canagliflozin mitigates ferroptosis and improves myocardial oxidative stress in mice with diabetic cardiomyopathy

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 14, 2022

Canagliflozin (Cana), an anti-diabetes drug belongs to sodium-glucose cotransporter 2 inhibitor, is gaining interest because of its extra cardiovascular benefits. Ferroptosis a new mode cell death, which can promote the occurrence diabetic cardiomyopathy (DCM). Whether Cana alleviate DCM by inhibiting ferroptosis focus this study. Here, we induced models in C57BL6 mice and treated with Cana. Meanwhile, order exclude hypoglycemic effect, high glucose model H9C2 cells were established. In vivo study, observed that could effectively damage cardiac function mice, including increasing lactate dehydrogenase (LDH) troponin I (cTnI), alleviating myocardial fiber breakage, inflammation, collagen deposition mitochondrial structural disorder. We evaluated reactive oxygen species (ROS) levels DCFH-DA BODIPY 581/591 C11, vitro reduced ROS lipid glucose. JC-1 fluorochrome assay showed decreased membrane potential (MMP) was increased Furthermore, inhibitory effects on oxidative stress verified protein carbonyl (PCO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH). As key inducer ferroptosis, total iron Fe 2+ be inhibited both . addition, western blot results indicated expression ferritin heavy-chain (FTN-H) down-regulated, cystine-glutamate antiporter (xCT) up-regulated cells, suggesting inhibit balancing homeostasis promoting system Xc - /GSH/GPX4 axis DCM. These findings underscore fact plays important role development progression targeting may novel strategy for prevention treatment. conclusion, exert some benefits attenuating ferroptosis.

Language: Английский

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SGLT2-inhibitors in diabetic patients with severe aortic stenosis and cardiac damage undergoing transcatheter aortic valve implantation (TAVI)

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 21, 2024

A substantial number of patients with severe aortic stenosis (AS) undergoing transcatheter valve implantation (TAVI) experience adverse events after TAVI, health care expenditure. We aimed to investigate cardiac remodeling and long-term outcomes in diabetic AS, left ventricular ejection fraction (LVEF) < 50%, extra-valvular damage (EVCD) TAVI treated sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus other glucose-lowering strategies (no-SGLT2i users). Multicenter international registry consecutive LVEF EVCD TAVI. Based on therapy at hospital discharge, were stratified SGLT2i no-SGLT2i users. The primary endpoint was a composite all-cause death heart failure (HF)-hospitalization (major cardiovascular events, MACE) 2-year follow-up. Secondary included death, HF hospitalization. study population 311 patients, among which 24% Within 1-year users experienced higher rate LV recovery (p = 0.032), especially those baseline ≤ 30% 0.026), despite the lower LVEF. Patients not more likely progress worse stage over time 0.018). At follow-up, use associated MACE, hospitalization 0.01 for all). After adjusting confounding factors, emerged as an independent predictor reduced MACE (HR 0.45; 95% CI 0.17–0.75; p 0.007), 0.51; 0.25–0.98; 0.042) HF-hospitalization 0.40; 0.27–0.62; 0.004). In favorable risk

Language: Английский

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In-hospital arrhythmic burden reduction in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: Insights from the SGLT2-I AMI PROTECT study

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Sept. 27, 2022

Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) have shown significant cardiovascular benefits in patients with and without type diabetes mellitus (T2DM). They also gained interest for their potential anti-arrhythmic role ability to reduce the occurrence of atrial fibrillation (AF) ventricular arrhythmias (VAs) T2DM heart failure patients.To investigate in-hospital new-onset cardiac a cohort presenting acute myocardial infarction (AMI) treated SGLT2-i vs. other oral anti-diabetic agents (non-SGLT2-i users).Patients from SGLT2-I AMI PROTECT registry (NCT05261867) were stratified according use before admission AMI, divided into users non-SGLT2-i users. In-hospital outcomes included (NOCAs), defined as composite AF sustained tachycardia (VT) and/or (VF) during hospitalization.The study population comprised 646 categorized (111 patients) (535 patients). had lower rate NOCAs compared (6.3 15.7%, p = 0.010). Moreover, was associated VT/VF considered individually (p 0.032). In multivariate logistic regression model, after adjusting all confounding factors, identified an independent predictor (OR 0.35; 95%CI 0.14-0.86; 0.022). At multinomial regression, confounders, therapy remained 0.20; 0.04-0.97; 0.046) but not occurrence.In patients, risk arrhythmic events hospitalization AMI. particular, primary effect expressed reduction VAs. These findings emphasize cardioprotective effects setting beyond glycemic control.Data are part observational international registry: PROTECT. ClinicalTrials.gov, identifier: NCT05261867.

Language: Английский

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Impact of SGLT2-inhibitors on contrast-induced acute kidney injury in diabetic patients with acute myocardial infarction with and without chronic kidney disease: Insight from SGLT2-I AMI PROTECT registry

Diabetes Research and Clinical Practice, Journal Year: 2023, Volume and Issue: 202, P. 110766 - 110766

Published: June 3, 2023

Language: Английский

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Obesity, diabetes mellitus, and cardiometabolic risk: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2023

Obesity Pillars, Journal Year: 2023, Volume and Issue: 5, P. 100056 - 100056

Published: Jan. 28, 2023

This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) is intended to provide clinicians an overview of type 2 diabetes mellitus (T2DM), obesity-related cardiometabolic risk factor.

Language: Английский

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Hypertrophic cardiomyopathy dysfunction mimicked in human engineered heart tissue and improved by sodium–glucose cotransporter 2 inhibitors

Cardiovascular Research, Journal Year: 2024, Volume and Issue: 120(3), P. 301 - 317

Published: Jan. 18, 2024

Abstract Aims Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy, often caused by pathogenic sarcomere mutations. Early characteristics of HCM are diastolic dysfunction and hypercontractility. Treatment to prevent mutation-induced cardiac lacking. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) a group antidiabetic drugs that recently showed beneficial cardiovascular outcomes in patients with acquired forms heart failure. We here studied if SGLT2i represent potential therapy correct cardiomyocyte induced an mutation. Methods results Contractility was measured human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) harbouring mutation cultured 2D 3D engineered tissue (EHT). Mutations gene encoding β-myosin heavy chain (MYH7-R403Q) or troponin T (TNNT2-R92Q) were investigated. In 2D, intracellular [Ca2+], action ion currents determined. mutations hiPSC-CMs impaired relaxation increased force, mimicking early features observed HCM. enhance hiPSC-CMs, larger extent compared control hiPSC-CMs. Moreover, SGLT2i-effects on R403Q EHT culture duration, i.e. maturation. Canagliflozin’s effects more pronounced than empagliflozin dapagliflozin. acutely altered Ca2+ handling Analyses SGLT2i-mediated mechanisms may underlie enhanced mutant excluded SGLT2, Na+/H+ exchanger, peak late Nav1.5 currents, L-type current, but indicate important role for Na+/Ca2+ exchanger. Indeed, electrophysiological measurements hiPSC-CM exchange current. Conclusion (canagliflozin &gt; dapagliflozin empagliflozin) EHT, especially upon prolonged culture.

Language: Английский

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Comparative Effectiveness of Individual Sodium-Glucose Cotransporter 2 Inhibitors

JAMA Internal Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Importance Evidence on cardiovascular benefits and safety of sodium-glucose cotransporter 2 (SGLT-2) inhibitors is mainly from placebo-controlled trials. Therefore, the comparative effectiveness individual SGLT-2 remain unknown. Objective To compare use canagliflozin or dapagliflozin with empagliflozin for a composite outcome (myocardial infarction [MI] stroke), heart failure hospitalization, MI, stroke, all-cause death, outcomes, including diabetic ketoacidosis (DKA), lower-limb amputation, bone fracture, severe urinary tract infection (UTI), genital whether effects differed by dosage disease (CVD) history. Design, Setting, Participants This study using target trial emulation included adults type diabetes (T2D) 3 US claims databases data August 2014 through June 2020. The was conducted 2023 to July 2024, follow-up period up 8 years, analysis completed in 2024. Exposures First dispensing canagliflozin, dapagliflozin, without any during prior 365 days. Main outcomes measures Database-specific models were weighted propensity score matching-weights adjust 129 confounders. Hazard ratios 95% CIs estimated Cox proportional hazards models. HRs pooled across fixed-effect meta-analysis. Results : Across databases, 232 890 patients receiving 881 295 043 identified. Compared initiators, those less likely have diabetes-related conditions history CVD at baseline. For MI/stroke risk, both (HR, 0.98; CI, 0.91-1.05) 0.95; 0.89-1.03) comparable empagliflozin. initiators had higher risk 1.19; 1.02-1.39), particularly low dose 5 mg 1.30; 1.12-1.50). These findings consistent subgroups events, compared empagliflozin, lower infections 0.94; 0.91-0.97) but UTIs 1.13; 1.03-1.24), risks 0.92; 0.89-0.95) DKA 0.78; 0.68-0.90). Conclusions Relevance found that demonstrated clinically effective doses, though low-dose showed reduced benefit hospitalization

Language: Английский

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Kidney outcomes in patients with diabetes mellitus did not differ between individual sodium-glucose cotransporter-2 inhibitors

Kidney International, Journal Year: 2022, Volume and Issue: 102(5), P. 1147 - 1153

Published: Aug. 9, 2022

Language: Английский

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New Insights into the Use of Empagliflozin—A Comprehensive Review

Biomedicines, Journal Year: 2022, Volume and Issue: 10(12), P. 3294 - 3294

Published: Dec. 19, 2022

Empagliflozin is a relatively new drug that, as an inhibitor of the sodium–glucose cotransporter 2 (SGLT2), causes increased urinary glucose excretion and thus contributes to improved glycemic control, better metabolism, reduced glucotoxicity insulin resistance. Although its original use was induce hypoglycemic effect in patients with type diabetes mellitus (T2DM), empagliflozin has also shown number other beneficial effects by demonstrating nephroprotective effect, it proven be breakthrough treatment heart failure (HF). been reduce hospitalizations for HF deaths from cardiovascular causes. reduces incidence renal events, including death causes, well risk end-stage failure. appears fairly well-tolerated safe drug. In inadequate used monotherapy or adjunct therapy effectively lowers fasting blood glucose, postprandial average daily levels, glycated hemoglobin A1C (HbA1C) leads significant weight reduction T2DM. Unfortunately, there are some limitations, e.g., severe hypersensitivity reaction glomerular filtration rate (GFR) < 30 mL/min/1.73 m2. As any drug, characterized several side among which symptomatic hypotension, troublesome genital fungal infections, tract infections rare ketoacidosis characteristic.

Language: Английский

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