The pleiotropic effects of glucagon-like peptide-1 receptor agonists in patients with metabolic dysfunction-associated steatohepatitis: a review for gastroenterologists DOI
Naim Alkhouri, Michael Charlton, Meagan Gray

et al.

Expert Opinion on Investigational Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) or glucagon have emerged as promising agents to treat metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic steatohepatitis (MASH). Although the beneficial effects of GLP-1RAs on glycemic control weight are well-established, clinicians may be unfamiliar with other potential benefits this class. We examined pleiotropic how they relate gastroenterologists for MASLD/MASH treatment. Our narrative review English articles included four (subcutaneous semaglutide, liraglutide, dulaglutide, efpeglenatide), a GLP-1/GIP agonist (tirzepatide), GLP-1/glucagon (survodutide), MASLD/MASH, related disorders, clinical management, treatment outcomes landscape. In Phase I - III trials, associated clinically relevant hepatic improvements including MASH resolution, fat reduction, preventing worsening fibrosis. Effects cardiometabolic parameters align type 2 diabetes/obesity data, comprising substantial in glycemic, weight, cardiovascular outcomes. Promising data also suggest common comorbidities, obstructive sleep apnea, polycystic ovary syndrome, chronic kidney disease, heart failure preserved ejection fraction.GLP-1RAs represent valuable pharmacotherapeutic option managing individuals comorbid conditions.

Language: Английский

Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity DOI Open Access
Daniel J. Drucker

Diabetes Care, Journal Year: 2024, Volume and Issue: unknown

Published: June 6, 2024

The development of glucagon-like peptide 1 receptor agonists (GLP-1RA) for type 2 diabetes and obesity was followed by data establishing the cardiorenal benefits GLP-1RA in select patient populations. In ongoing trials investigators are interrogating efficacy these agents new indications, including metabolic liver disease, peripheral artery Parkinson Alzheimer disease. success GLP-1–based medicines has spurred molecular entities combinations with unique pharmacokinetic pharmacodynamic profiles, exemplified tirzepatide, a GIP-GLP-1 coagonist. Simultaneously, investigational molecules such as maritide block GIP activate GLP-1 receptor, whereas retatrutide survodutide enable simultaneous activation glucagon receptors. Here I highlight evidence medicines, while discussing that inform safety, focusing on muscle strength, bone density fractures, exercise capacity, gastrointestinal motility, retained gastric contents anesthesia, pancreatic biliary tract disorders, risk cancer. Rapid progress highly efficacious anticipated differentiation newer subsets will provide greater opportunities use personalized medicine approaches to improve health people living cardiometabolic disorders.

Language: Английский

Citations

96
Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials DOI
Mikhail Kosiborod, John Deanfield,

Richard Pratley

et al.

The Lancet, Journal Year: 2024, Volume and Issue: 404(10456), P. 949 - 961

Published: Aug. 30, 2024

Language: Английский

Citations

71
Obesity and cardiovascular disease: an ESC clinical consensus statement DOI Creative Commons
Konstantinos C. Koskinas, Emeline M. Van Craenenbroeck, Charalambos Antoniades

et al.

European Heart Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

The global prevalence of obesity has more than doubled over the past four decades, currently affecting a billion individuals. Beyond its recognition as high-risk condition that is causally linked to many chronic illnesses, been declared disease per se results in impaired quality life and reduced expectancy. Notably, two-thirds obesity-related excess mortality attributable cardiovascular disease. Despite increasingly appreciated link between broad range manifestations including atherosclerotic disease, heart failure, thromboembolic arrhythmias, sudden cardiac death, underrecognized sub-optimally addressed compared with other modifiable risk factors. In view major repercussions epidemic on public health, attention focused population-based personalized approaches prevent weight gain maintain healthy body from early childhood throughout adult life, well comprehensive loss interventions for persons established obesity. This clinical consensus statement by European Society Cardiology discusses current evidence epidemiology aetiology obesity; interplay obesity, factors conditions; management patients strategies lifestyle changes, interventional procedures, anti-obesity medications particular focus their impact cardiometabolic outcomes. document aims raise awareness factor provide guidance implementing evidence-based practices prevention optimal within context primary secondary prevention.

Language: Английский

Citations

58
Diabetes mellitus—Progress and opportunities in the evolving epidemic DOI
E. Dale Abel, Anna L. Gloyn, Carmella Evans‐Molina

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(15), P. 3789 - 3820

Published: July 1, 2024

Language: Английский

Citations

51
Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial DOI Creative Commons
Mikhail Kosiborod, Subodh Verma, Barry A. Borlaug

et al.

Circulation, Journal Year: 2023, Volume and Issue: 149(3), P. 204 - 216

Published: Nov. 12, 2023

Patients with heart failure (HF) preserved ejection fraction (HFpEF) and obesity experience a high burden of symptoms functional impairment, poor quality life. In the STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure Obesity), once-weekly semaglutide 2.4 mg improved symptoms, physical limitations, exercise function, reduced inflammation body weight. This prespecified analysis investigated effects on primary confirmatory secondary end points across range Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at baseline all key summary individual KCCQ domains.

Language: Английский

Citations

49
Effect of Semaglutide on Cardiac Structure and Function in Patients With Obesity-Related Heart Failure DOI Creative Commons

Scott D. Solomon,

John W. Ostrominski, Xiaowen Wang

et al.

Journal of the American College of Cardiology, Journal Year: 2024, Volume and Issue: 84(17), P. 1587 - 1602

Published: Aug. 30, 2024

Obesity is associated with adverse cardiac remodeling and a key driver for the development progression of heart failure (HF). Once-weekly semaglutide (2.4 mg) has been shown to improve HF-related symptoms physical limitations, body weight, exercise function in patients obesity-related preserved ejection fraction (HFpEF), but effects on structure this population remain unknown.

Language: Английский

Citations

35
Semaglutide and NT-proBNP in Obesity-Related HFpEF DOI Creative Commons
Mark C. Petrie, Barry A. Borlaug,

Javed Butler

et al.

Journal of the American College of Cardiology, Journal Year: 2024, Volume and Issue: 84(1), P. 27 - 40

Published: May 13, 2024

The glucagon-like peptide-1 receptor agonist, semaglutide, improved health status and reduced body weight in patients with obesity-related heart failure (HF) preserved ejection fraction (HFpEF) the STEP-HFpEF Program. Whether benefits were due to mechanical unloading or effects on HF pathobiology is uncertain. Determine if semaglutide 2.4 mg N-terminal pro-brain natriuretic peptide (NTproBNP) HFpEF compare treatment responses by baseline NTproBNP. Prespecified secondary analysis of pooled data from two double-blind, placebo-controlled, randomized trials (STEP-HFpEF DM) testing HFpEF. main outcomes change NTproBNP at 52 weeks dual primary endpoints KCCQ-CSS 1145 randomized. Semaglutide, compared placebo, (estimated ratio 0.82 [95% CI: 0.74-; 0.91]; P = 0.0002). Improvements more pronounced those higher vs lower difference: tertile 1: 4.5 points 0.8–8.2], 2: 6.2 2.4–10.0], 3: 11.9 8.1–15.7]; interaction 0.02; as a continuous variable: 0.004). Reductions consistent across levels (interaction 0.21). In HFpEF, Participants had similar degree loss but experienced larger reductions HF-related symptoms physical limitations than

Language: Английский

Citations

30
Pharmacotherapy for obesity: moving towards efficacy improvement DOI Creative Commons
Walmir Coutinho, Bruno Halpern

Diabetology & Metabolic Syndrome, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 3, 2024

Abstract Obesity is a chronic, recurring, progressive disease and major public health problem associated with several other diseases that lead to disability, morbidity, mortality. The prevalence of obesity has increased at pandemic levels, along increasing weight-related comorbidities deaths worldwide. Lifestyle interventions alone provide clinically significant long-term weight loss in only small proportion individuals, bariatric surgery not suitable or desirable for all patients. Historically, anti-obesity medications achieved mean efficacy between 5 10%, which significantly impacted risk factors, but the average these remained lower than expected by both patients care professionals eventually curbed use. Moreover, there no direct evidence on impact cardiovascular outcomes. Semaglutide newer medication changes overall landscape, as phase 3 studies show near 15% threshold proportions greater 20%. In this review, we focus currently available medications, discuss results semaglutide, present perspectives future treatment after semaglutide.

Language: Английский

Citations

22
Prevention of cardiorenal complications in people with type 2 diabetes and obesity DOI Creative Commons
Daniel J. Drucker

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(2), P. 338 - 353

Published: Jan. 9, 2024

Language: Английский

Citations

22
Obesity and cardiovascular disease: an ESC clinical consensus statement DOI Creative Commons
Konstantinos C. Koskinas, Emeline M. Van Craenenbroeck, Charalambos Antoniades

et al.

European Journal of Preventive Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

The global prevalence of obesity has more than doubled over the past four decades, currently affecting a billion individuals. Beyond its recognition as high-risk condition that is causally linked to many chronic illnesses, been declared disease per se results in impaired quality life and reduced expectancy. Notably, two-thirds obesity-related excess mortality attributable cardiovascular disease. Despite increasingly appreciated link between broad range manifestations including atherosclerotic disease, heart failure, thromboembolic arrhythmias, sudden cardiac death, underrecognized sub-optimally addressed compared with other modifiable risk factors. In view major repercussions epidemic on public health, attention focused population-based personalized approaches prevent weight gain maintain healthy body from early childhood throughout adult life, well comprehensive loss interventions for persons established obesity. This clinical consensus statement by European Society Cardiology discusses current evidence epidemiology aetiology obesity; interplay obesity, factors conditions; management patients strategies lifestyle changes, interventional procedures, anti-obesity medications particular focus their impact cardiometabolic outcomes. document aims raise awareness factor provide guidance implementing evidence-based practices prevention optimal within context primary secondary prevention.

Language: Английский

Citations

21