Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 16, 2024

BackgroundObesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking respect to its effects on cardiovascular outcomes.MethodsIn this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in 1:1 ratio, 731 patients failure, an fraction at least 50%, body-mass index (the kilograms divided by square height meters) 30 receive tirzepatide (up 15 mg subcutaneously once per week) or placebo for 52 weeks. The two primary end points were composite adjudicated death from worsening heart-failure event (assessed time-to-first-event analysis) change baseline weeks Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range 0 100, higher indicating better quality life).ResultsA total 364 assigned group 367 group; median duration follow-up was 104 Adjudicated occurred 36 (9.9%) 56 (15.3%) (hazard 0.62; 95% confidence interval [CI], 0.41 0.95; P=0.026). Worsening events 29 (8.0%) (14.2%) 0.54; CI, 0.34 0.85), 8 (2.2%) 5 (1.4%), respectively 1.58; 0.52 4.83). At weeks, mean (±SD) KCCQ-CSS 19.5±1.2 as compared 12.7±1.3 (between-group difference, 6.9; 3.3 10.6; P<0.001). Adverse (mainly gastrointestinal) leading discontinuation trial drug 23 (6.3%) (1.4%) group.ConclusionsTreatment led lower than improved health status obesity. (Funded Eli Lilly; SUMMIT ClinicalTrials.gov number, NCT04847557.)

Language: Английский

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Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure

Journal of the American College of Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium–Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2484 - 2484

Published: Feb. 20, 2024

Different multifactorial pathophysiological processes are involved in the development of heart failure (HF), including neurohormonal dysfunction, hypertrophy cardiomyocytes, interstitial fibrosis, microvascular endothelial inflammation, pro-thrombotic states, oxidative stress, decreased nitric oxide (NO) bioavailability, energetic epicardial coronary artery lesions, rarefaction and, finally, cardiac remodeling. While different pharmacological strategies have shown significant cardiovascular benefits HF with reduced ejection fraction (HFrEF), there is a residual unmet need to fill gap terms knowledge mechanisms and efficacy outcomes agents preserved (HFpEF). Recently, type-2 sodium–glucose transporter inhibitors (SGLT2i) been contribute reduction composite outcome hospitalizations mortality across entire spectrum fraction. Moreover, glucagon-like peptide-1 receptor agonists (GLP1-RA) demonstrated patients high risk, excess body weight or obesity HF, particular HFpEF. In this review, we will discuss biological pathways potentially action SGLT2i GLP1-RA, which may explain their effective roles treatment as well potential implications use these agents, also combination therapies clinical practice.

Language: Английский

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Emerging Pharmacotherapies for Obesity: A Systematic Review

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 77(1), P. 100002 - 100002

Published: Sept. 20, 2024

The history of anti-obesity pharmacotherapies is marked by disappointments, often entangled with societal pressure promoting weight loss and the conviction that excess body signifies a lack willpower. However, categories emerging generate hope to reduce obesity rates. This systematic review phase 2 3 trials in adults overweight/obesity investigates effect novel pharmacotherapies, compared placebo/control or Food Drug Administration-approved medication, through searching Medline, Embase, ClinicalTrials.gov (2012-2024). We identified 53 trials, 36 drugs combinations thereof four withdrawn terminated trials. Oral semaglutide 50 mg only medication has completed trial. There are 14 ongoing on glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) (ecnoglutide, orforglipron, TG103), GLP-1 RA/amylin agonist (CagriSema), GLP-1/glucagon RAs (mazdutide, survodutide), GLP-1/glucose-dependent insulinotropic polypeptide glucagon RA (retatrutide), dapagliflozin, combination sibutramine/topiramate. Completed incretin-based therapies showed mean percent 7.4-24.2%. Almost half undergoing were incretin analogs. drug pipeline expanding rapidly, most promising results reported Data mortality obesity-related complications, such as cardio-renal-metabolic events, needed. Moreover, long-term follow-up data safety efficacy maintenance along studies focused under-represented populations, cost-effectiveness assessments, availability, needed bridge care gap for patients obesity. Significance Statement Obesity epidemic 21st century. Except newer injectable medications, suboptimal have been available clinician's armamentarium. alternatives agents populate therapeutic pipeline. identifies state mechanism action having clinical information provided herein furthers understanding management, implying direct implications stimulating research initiatives.

Language: Английский

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Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: Dec. 19, 2023

Abstract Objective We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve patients type 2 diabetes (T2D) stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular is inflammation epicardial adipose tissue (EAT). Since latter often increased patients, it could play a role microvascular dysfunction. It also well known SGLT-2i modify metabolism. aimed investigate effects dapagliflozin on metabolism and visceral subcutaneous thickness T2D verify whether these changes explain observed flow. Methods performed single-center, prospective, randomized, double-blind, controlled clinical trial 14 randomized 1:1 (10 mg daily) or placebo. (epicardial, mediastinal, perirenal) glucose uptake were assessed at baseline 4 weeks after initiation 2-deoxy-2-[ 18 F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. Results two groups well-matched characteristics (age, duration, HbA1c, BMI, renal heart function). Dapagliflozin significantly reduced EAT 19% (p = 0.03). There was significant 21.6% reduction clamp group compared placebo 0.014). no thickness/metabolism other depots explored. Conclusions SGLT-2 inhibition selectively reduces suggesting inflammation. This reserve, providing new insights into benefits.

Language: Английский

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Excessive accumulation of epicardial adipose tissue promotes microvascular obstruction formation after myocardial ischemia/reperfusion through modulating macrophages polarization

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

Published: July 5, 2024

Abstract Background Owing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized an independent factor unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT pathogenesis MVO formation individuals with ST-segment elevation (STEMI) remains unclear. The objective study evaluate correlation between accumulation measured by cardiac magnetic resonance (CMR) STEMI patients clarify underlying mechanisms involved this relationship. Methods Firstly, we utilized CMR technique explore association distribution quantity STEMI. Then mouse model depletion how affected under circumstances ischemia/reperfusion (I/R) injury. We further investigated immunomodulatory effect on macrophages through co-culture experiments. Finally, searched therapeutic strategies targeting prevent formation. Results increase left atrioventricular mass index was independently associated also found that increased circulating levels DPP4 high activity seemed be increase. acted pro-inflammatory mediator boosting transition towards inflammatory phenotype I/R injury secreting EVs. Furthermore, our declared potential effects GLP-1 receptor agonist GLP-1/GLP-2 dual prevention were at least partially ascribed impact modulation. Conclusions Our work first time demonstrated excessive promoted promoting polarization state phenotype. identified very promising strategy, agonist, following

Language: Английский

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The effect of sodium-glucose co-transporter-2 inhibitors on markers of subclinical atherosclerosis

Annals of Medicine, Journal Year: 2023, Volume and Issue: 55(2)

Published: Dec. 12, 2023

Background Despite the widespread use of classical cholesterol-lowering drugs to mitigate adverse impacts dyslipidaemia on atherosclerosis, many patients still face a substantial residual risk developing atherosclerotic cardiovascular disease (CVD). This is partially attributed non-traditional pathophysiological pathways. Latest evidence suggests that sodium glucose co-transporter-2 (SGLT2) inhibitors are beneficial for suffering from type 2 diabetes mellitus (T2DM) or established CVD by reducing morbidity and mortality. However, underlying mechanisms this benefit have not been clearly elucidated. It has hypothesized one possible mechanism could be attenuation subclinical atherosclerosis (SA) progression.

Language: Английский

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Epicardial adipose tissue, metabolic disorders, and cardiovascular diseases: recent advances classified by research methodologies

MedComm, Journal Year: 2023, Volume and Issue: 4(6)

Published: Oct. 24, 2023

Epicardial adipose tissue (EAT) is located between the myocardium and visceral pericardium. The unique anatomy physiology of EAT determines its great potential in locally influencing adjacent tissues such as coronary arteries. Classified by research methodologies, this study reviews latest progress on role cardiovascular diseases (CVDs), particularly patients with metabolic disorders. Studies based imaging techniques demonstrated that increased amount disorders associated higher risk CVDs mortality. Then, in-depth profiling studies indicate remodeled may serve a local mediator deleterious effects cardiometabolic conditions plays crucial CVDs. Further, vitro coculture provided preliminary evidence paracrine effect cardiomyocytes can promote occurrence progression Considering important CVDs, targeting might be strategy to reduce risks. Several interventions have been proved effective reducing amount. Our review provides valuable insights relationship EAT, disorders, well an overview methodological constructs EAT-related studies.

Language: Английский

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Relationship between epicardial adipose tissue and coronary atherosclerosis by CCTA in young adults (18–45)

American Journal of Preventive Cardiology, Journal Year: 2024, Volume and Issue: 19, P. 100711 - 100711

Published: July 20, 2024

Epicardial adipose tissue (EAT) is implicated in the pathogenesis and progression of coronary artery disease (CAD). Limited data exists on interplay between EAT atherosclerosis young individuals. Our study aims to explore relationship CAD a cohort.

Language: Английский

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Heart Failure and Obesity

Journal of the American College of Cardiology, Journal Year: 2024, Volume and Issue: 84(17), P. 1666 - 1677

Published: Oct. 1, 2024

Language: Английский

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