Pharmacotherapy of Weight‐loss and Obesity with a Focus on GLP 1‐Receptor Agonists DOI

Merle Myerson,

Rodis Paparodis

The Journal of Clinical Pharmacology, Journal Year: 2024, Volume and Issue: 64(10), P. 1204 - 1221

Published: June 26, 2024

Obesity is a disease of epidemic proportions in the United States and contributes to morbidity mortality for large part population. In addition, financial costs this society are high. Lifestyle modifications key prevention treatment but adherence long-term success have been challenging. Bariatric surgery has available pharmacologic approaches, first developed 1950s, continue be an option; however, existing formulations not provided optimal clinical efficacy had many concerning adverse effects. Over last decade, glucagon-like peptide-1 (GLP-1) receptor agonists, novel group medications type 2 diabetes, were found produce significant weight loss. Several formulations, at higher doses, received FDA approval obesity or those overweight with weight-related co-morbidities. More hormone-based therapies being developed, some dual triple-receptor agonist activity. Their use, without questions concerns as safety efficacy, problems cost reimbursement, how their use may intersect public health efforts manage epidemic. This review will focus on GLP-1 agonists currently used loss discuss pharmacology, pertinent research findings establishing benefits risks, issues prescribing these medications, perspective from point view.

Language: Английский

Metabolic dysfunction-associated steatotic liver disease in adults DOI
Daniel Q. Huang, Vincent Wai–Sun Wong, Mary E. Rinella

et al.

Nature Reviews Disease Primers, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 6, 2025

Language: Английский

Citations

3
The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update DOI Creative Commons
Agnieszka Jakubowska, Carel W. le Roux, Adie Viljoen

et al.

Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 39(1), P. 12 - 22

Published: Feb. 15, 2024

Obesity is the fifth leading risk factor for global deaths with numbers continuing to increase worldwide. In last 20 years, emergence of pharmacological treatments obesity based on gastrointestinal hormones has transformed therapeutic landscape. The successful development glucagon-like peptide-1 (GLP-1) receptor agonists, followed by synergistic combined effect glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists achieved remarkable weight loss and glycemic control in those diseases type 2 diabetes. multiple cardiometabolic benefits include improving control, lipid profiles, blood pressure, inflammation, hepatic steatosis. 2023 phase double-blind, randomized controlled trial evaluating a GLP-1/GIP/glucagon triagonist (retatrutide) patients disease reported 24.2% at 48 weeks 12 mg retatrutide. This review evaluates current available evidence GLP-1 dual GLP-1/GIP co-agonists focus triagonists discusses potential future research directions.

Language: Английский

Citations

15
Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis DOI Creative Commons
Eric Lawitz,

Mandy Fraessdorf,

Guy Neff

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 81(5), P. 837 - 846

Published: June 8, 2024

Survodutide is a glucagon/glucagon-like peptide-1 receptor dual agonist in development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). We investigated pharmacokinetic and safety profile survodutide people with cirrhosis.

Language: Английский

Citations

14
The role of glucagon‐like peptide‐1 receptor agonists in metabolic dysfunction‐associated steatohepatitis DOI Creative Commons
Manal F. Abdelmalek, Stephen A. Harrison, Arun J. Sanyal

et al.

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: 26(6), P. 2001 - 2016

Published: March 21, 2024

Despite its considerable and growing burden, there are currently no Food Drug Administration-approved treatments for metabolic dysfunction-associated steatotic liver disease or progressive form, steatohepatitis (MASH). Several glucagon-like peptide-1 receptor agonists (GLP-1RAs) other agents in various phases of clinical development use MASH; an ideal therapy should reduce fat content, improve chronic disease, help mitigate comorbidities decrease all-cause mortality. Because interconnected mechanisms, disease/MASH often coexists with type 2 diabetes (T2D), obesity cardiovascular disease. Various GLP-1RAs T2D, two, liraglutide semaglutide, approved overweight obesity. glucose levels body weight outcomes people T2D who at high risk In addition, have been reported to content enzymes, oxidative stress hepatic de novo lipogenesis the histopathology MASH. Weight loss may contribute these effects; however, exact mechanisms unknown. Adverse events that commonly associated include vomiting, nausea diarrhoea. There is a lack evidence from meta-analyses regarding increased acute pancreatitis forms cancer GLP-1RAs. Large-scale, phase 3 trials, which will provide definitive data on potential therapies MASH, ongoing. Given spectrum modalities under investigation, it hoped trials support identification pharmacotherapies benefit patients

Language: Английский

Citations

12
Preventing the progression of cirrhosis to decompensation and death DOI
Cándid Villanueva, Dhiraj Tripathi, Jaime Bosch

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Language: Английский

Citations

1
Type 2 Diabetes Mellitus: A Comprehensive Review of Pathophysiology, Comorbidities, and Emerging Therapies DOI
Aditi Singh,

Sucharita Shadangi,

Pulkit Kr. Gupta

et al.

Comprehensive physiology, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 1, 2025

ABSTRACT Humans are perhaps evolutionarily engineered to get deeply addicted sugar, as it not only provides energy but also helps in storing fats, which survival during starvation. Additionally, sugars (glucose and fructose) stimulate the feel‐good factor, they trigger secretion of serotonin dopamine brain, associated with reward sensation, uplifting mood general. However, when consumed excess, contributes imbalance, weight gain, obesity, leading onset a complex metabolic disorder, generally referred diabetes. Type 2 diabetes mellitus (T2DM) is one most prevalent forms diabetes, nearly affecting all age groups. T2DM clinically diagnosed cardinal sign chronic hyperglycemia (excessive sugar blood). Chronic hyperglycemia, coupled dysfunctions pancreatic β‐cells, insulin resistance, immune inflammation, further exacerbate pathology T2DM. Uncontrolled T2DM, major public health concern, significantly toward progression several micro‐ macrovascular diseases, such diabetic retinopathy, nephropathy, neuropathy, atherosclerosis, cardiovascular including cancer. The current review discusses epidemiology, causative factors, pathophysiology, comorbidities, existing emerging therapies related It future roadmap for alternative drug discovery management

Language: Английский

Citations

1
Global burden and future trends of metabolic dysfunction-associated steatotic liver disease: 1990-2021 to 2045 DOI Creative Commons

Chengxia Kan,

Kexin Zhang, Yuqun Wang

et al.

Annals of Hepatology, Journal Year: 2025, Volume and Issue: unknown, P. 101898 - 101898

Published: March 1, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly non-alcoholic fatty disease, is a growing global health challenge. This study examines the burden of MASLD from 1990 to 2021 and projects data for 2045. Using Global Burden Disease (GBD) Study 2021, analyzed across 204 countries focusing on prevalence, incidence, deaths, disability-adjusted life years (DALYs). Linear Joinpoint regression assessed trends, an age-period-cohort model evaluated outcomes, Bayesian forecasted future cases. In approximately 1.27 billion people globally had MASLD, with higher prevalence in males (51.41%). There were 48.35 million new cases, primarily (52.24%). The age-standardized rate (ASPR) increased 12,085.09 15,018.07 per 100,000 (AAPC 0.71). incidence (ASIR) rose 475.54 593.28 caused 138,328 females experiencing mortality (52.18%). East Asia, South North Africa/Middle highest rates, while Western Europe showed fastest growth. By 2045, ASIR projected reach 928.10 100,000, resulting 667.58 predominantly affecting males. poses significant notable gender regional disparities. increase by 2045 underscores need urgent public interventions targeted strategies mitigate this epidemic.

Language: Английский

Citations

1
Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now? DOI Creative Commons
Prathima Gogineni, Eka Melson, Dimitris Papamargaritis

et al.

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: 25(7), P. 801 - 818

Published: May 2, 2024

Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have changed the landscape of type 2 diabetes (T2D) management due to their cardio-renal benefits, glucose-lowering efficacy and weight loss (WL) maintenance. However, response GLP-1 RA monotherapy is heterogeneous. Additionally, majority RAs are injectable treatments. Oral combinations with other entero-pancreatic hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon amylin) under development for T2D obesity management.

Language: Английский

Citations

8
MetALD: Does it require a different therapeutic option? DOI
George Marek, Harmeet Malhi

Hepatology, Journal Year: 2024, Volume and Issue: 80(6), P. 1424 - 1440

Published: May 31, 2024

New guidelines for the definitions of steatotic liver disease have named entity metabolic dysfunction and alcohol-associated (MetALD) as an overlap condition dysfunction–associated (MASLD) disease. There is a broad range therapeutics in all stages development MASLD, but these therapeutics, general, not been studied patients with significant ongoing alcohol use. In this review, we discuss current understanding endogenous exogenous risks MASLD MetALD. Rational strategies therapeutic intervention MetALD include biopsychosocial interventions, use cessation strategies, including medications disorder, judicious Therapeutics promise incretin-based therapies, FGF21 agonists, thyroid hormone receptor beta sodium-glucose co-transporter 2 inhibitors, agents to modify de novo lipogenesis. Currently, glucagon-like peptide 1 agonists peroxisome proliferator–activated γ largest body literature supporting their there paucity trials From existing studies, it clear if unique or combinatorial approach are needed Further elucidation safety benefits MASLD-related therapies paramount importance advancing carefully designed inclusive clinical trials.

Language: Английский

Citations

8
Pharmacotherapeutic options for metabolic dysfunction-associated steatotic liver disease: where are we today? DOI Creative Commons
Tobias Puengel, Frank Tacke

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: 25(9), P. 1249 - 1263

Published: June 12, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis and cardiometabolic risk factors like obesity, type 2 diabetes, dyslipidemia. Persistent metabolic injury may promote inflammatory processes resulting in steatohepatitis (MASH) fibrosis. Mechanistic insights helped to identify potential drug targets, thereby supporting the development of novel compounds modulating drivers.

Language: Английский

Citations

8