Medical management of obesity: unlocking the potential DOI Creative Commons
Angie S. Xiang, Priya Sumithran

Climacteric, Год журнала: 2025, Номер unknown, С. 1 - 5

Опубликована: Фев. 7, 2025

After a long and challenging history, there have finally been major breakthroughs in the development of effective obesity medications. Agents that act at receptors one or more gut hormones are achieving unprecedented weight reductions improvements cardiovascular risk factors, comparable to some bariatric surgical procedures. Importantly, is evidence beneficial effects on growing range conditions, including type 2 diabetes, fatty liver, chronic kidney disease, obstructive sleep apnea disease. Barriers access need be overcome allow standard care for match other diseases.

Язык: Английский

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

и другие.

Endocrinology and Metabolism, Год журнала: 2024, Номер 39(1), С. 12 - 22

Опубликована: Фев. 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.

Язык: Английский

Процитировано

17

Managing insulin resistance: the forgotten pathophysiological component of type 2 diabetes DOI

Muhammad Abdul-Ghani,

Pietro Maffei, Ralph A. DeFronzo

и другие.

The Lancet Diabetes & Endocrinology, Год журнала: 2024, Номер 12(9), С. 674 - 680

Опубликована: Авг. 1, 2024

Язык: Английский

Процитировано

15

New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists DOI Creative Commons
Ferenc Sztanek,

László Imre Tóth,

Attila Pető

и другие.

Biomedicines, Год журнала: 2024, Номер 12(6), С. 1320 - 1320

Опубликована: Июнь 13, 2024

Guidelines for the management of obesity and type 2 diabetes (T2DM) emphasize importance lifestyle changes, including a reduced-calorie diet increased physical activity. However, many people, these changes can be difficult to maintain over long term. Medication options are already available treat obesity, which help reduce appetite and/or caloric intake. Incretin-based peptides exert their effect through G-protein-coupled receptors, receptors glucagon-like peptide-1 (GLP-1) glucose-dependent insulinotropic polypeptide (GIP), glucagon peptide hormones important regulators insulin secretion energy metabolism. Understanding role intercellular signaling pathways inflammatory processes is essential development effective pharmacological agents in obesity. GLP-1 receptor agonists have been successfully used, but it assumed that effectiveness may limited by desensitization downregulation target receptor. A growing number new acting on incretin becoming everyday clinical practice, oral agonists, dual GLP-1/GIP agonist tirzepatide, other triple GLP-1/GIP/glucagon show further significant therapeutic potential. This narrative review summarizes effects different presents future prospects treatment T2DM

Язык: Английский

Процитировано

13

Recent advances in peptide-based therapies for obesity and type 2 diabetes DOI Creative Commons
Clifford J. Bailey, Peter R. Flatt, J. Michael Conlon

и другие.

Peptides, Год журнала: 2024, Номер 173, С. 171149 - 171149

Опубликована: Янв. 5, 2024

Options for the treatment of type 2 diabetes mellitus (T2DM) and obesity have recently been expanded by results several large clinical trials with incretin-based peptide therapies. Most these studies conducted glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, which is available as a once weekly subcutaneous injection daily tablet, injected dual tirzepatide, interacts receptors GLP-1 glucose-dependent insulinotropic polypeptide (GIP). In individuals T2DM therapies achieved reductions glycated haemoglobin (HbA1c) > 2% lowered body weight 10%. some studies, agents tested in non-diabetic, obese at much higher doses 15%. Emerging evidence suggests can also offer cardio-protective potentially reno-protective effects. Other early development, notably triple GLP-1/GIP/glucagon (retatrutide) combination semaglutide amylin analogue cagrilintide (CagriSema), shown strong efficacy. Although incretin incur adverse gastrointestinal effects are most patients mild-to-moderate transient but result cessation cases. Thus, efficacy new enhancing opportunity to control blood glucose improve obesity.

Язык: Английский

Процитировано

11

Non-canonical G protein signaling DOI Creative Commons
Bernd Nürnberg, Sandra Beer‐Hammer, Ellen Reisinger

и другие.

Pharmacology & Therapeutics, Год журнала: 2024, Номер 255, С. 108589 - 108589

Опубликована: Янв. 29, 2024

The original paradigm of classical - also referred to as canonical cellular signal transduction heterotrimeric G proteins (G protein) is defined by a hierarchical, orthograde interaction three players: the agonist-activated protein-coupled receptor (GPCR), which activates transducing protein, that in turn regulates its intracellular effectors. This receptor-transducer-effector concept was extended identification regulators and adapters such protein signaling (RGS), kinases like βARK, or GPCR-interacting arrestin are integrated into this process at different levels enable fine-tuning. Finally, atypical mechanisms regulators, together with discovery novel modulators, added new fascinating dimension transduction. heterogeneous group accessory modulators coined "activators signaling" (AGS) plays distinct roles non-canonical pathways. AGS contribute control essential functions cell development division, transport processes, secretion, autophagy movements. As such, they involved numerous biological processes crucial for diseases, diabetes mellitus, cancer, stroke, represent major health burdens. Although large number pathways has broadened spectrum communication system, their underlying mechanisms, functions, effects poorly understood. In review, we highlight discuss protein-dependent focus on inhibitory (Gi) transduction, review recent developments open questions, address potential approaches targeted pharmacological interventions.

Язык: Английский

Процитировано

9

Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities DOI Creative Commons
Clifford J. Bailey, Peter R. Flatt, J. Michael Conlon

и другие.

Peptides, Год журнала: 2025, Номер 187, С. 171380 - 171380

Опубликована: Март 11, 2025

Recent studies with peptide-based incretin herapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and dual tirzepatide that engages receptors for GLP-1 glucose-dependent insulinotropic polypeptide (GIP). Randomised clinical trials 'real-world' confirmed marked glucose-lowering weight-lowering efficacy of these agents across diverse populations. These include different ethnic groups, young elderly individuals without diabetes and/or overweight or obesity. also protections against development progression cardiovascular renal diseases are additive to benefits conferred by improved control blood glucose body weight. Emerging evidence suggests therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea possibly degenerative bone disorders cognitive decline. New incretin-based peptide in a long-acting glucagon (LY3324954), GLP-1/glucagon agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon (retatrutide, efocipegtrutide), combination amylin analogue cagrilintide (CagriSema), unimolecular GLP-1/amylin (amycretin), GIP antibody agonism (MariTide). The creation multi-targeting synthetic peptides provides opportunities management type 2 obesity as well new therapeutic approaches an expanding list associated co-morbidities. aim review is acquaint reader developments field from 2023 present (February 2025).

Язык: Английский

Процитировано

1

Enteroendocrine cell regulation of the gut-brain axis DOI Creative Commons
Joshua R. Barton, Anne Londregan, Tyler D. Alexander

и другие.

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Ноя. 7, 2023

Enteroendocrine cells (EECs) are an essential interface between the gut and brain that communicate signals about nutrients, pain, even information from our microbiome. EECs hormone-producing expressed throughout gastrointestinal epithelium have been leveraged by pharmaceuticals like semaglutide (Ozempic, Wegovy), terzepatide (Mounjaro), retatrutide (Phase 2) for diabetes weight control, linaclotide (Linzess) to treat irritable bowel syndrome (IBS) visceral pain. This review focuses on role of intestinal lumen brain. Canonically, environment through a variety hormones, dividing into separate classes based hormone each cell type secretes. Recent studies revealed more diverse profiles communication modalities including direct synaptic with peripheral neurons. known as neuropod rapidly relay via vagal primary sensory Further, this discusses complex processing machinery within EECs, receptors transduce intraluminal ion channel complement govern initiation propagation these signals. Deeper understanding EEC physiology is necessary safely devastating pervasive conditions obesity.

Язык: Английский

Процитировано

19

Emerging role of antidiabetic drugs in cardiorenal protection DOI Creative Commons

Wen-Jia Fu,

Jin-Ling Huo,

Zi‐Hui Mao

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Фев. 6, 2024

The global prevalence of diabetes mellitus (DM) has led to widespread multi-system damage, especially in cardiovascular and renal functions, heightening morbidity mortality. Emerging antidiabetic drugs sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 (DPP-4i) have demonstrated efficacy preserving cardiac function, both type diabetic non-diabetic individuals. To understand the exact impact these on cardiorenal protection underlying mechanisms, we conducted a comprehensive review recent large-scale clinical trials basic research focusing SGLT2i, GLP-1RAs, DPP-4i. Accumulating evidence highlights diverse mechanisms including glucose-dependent independent pathways, revealing their potential disease. This provides critical insights into protective effects DPP-4i underscores importance medications mitigating progression complications, broader implications beyond glycemic management.

Язык: Английский

Процитировано

7

Obesity and the gut microbiota: implications of neuroendocrine and immune signaling DOI Creative Commons
Marina Romaní‐Pérez, Rebeca Liébana-García,

Alejandra Flor‐Duro

и другие.

FEBS Journal, Год журнала: 2024, Номер unknown

Опубликована: Авг. 19, 2024

Obesity is a major health challenge due to its high prevalence and associated comorbidities. The excessive intake of diet rich in fat sugars leads persistent imbalance between energy expenditure, which increases adiposity. Here, we provide an update on relevant diet-microbe-host interactions contributing or protecting from obesity. In particular, focus how unhealthy diets shape the gut microbiota thus impact crucial intestinal neuroendocrine immune system functions. We describe these promote dysfunction gut-to-brain pathways involved food control postprandial metabolism elevate proinflammatory tone, promoting obesity metabolic complications. addition, examples this knowledge may inspire microbiome-based interventions, such as fecal transplants, probiotics, biotherapeutics, effectively combat obesity-related disorders. also discuss current limitations gaps research

Язык: Английский

Процитировано

7

The interplay of glucose-dependent insulinotropic polypeptide in adipose tissue DOI Creative Commons

Samrin Kagdi,

Sulayman A. Lyons, Jacqueline L. Beaudry

и другие.

Journal of Endocrinology, Год журнала: 2024, Номер 261(3)

Опубликована: Апрель 3, 2024

Adipose tissue was once known as a reservoir for energy storage but is now considered crucial organ hormone and flux with important effects on health disease. Glucose-dependent insulinotropic polypeptide (GIP) an incretin secreted from the small intestinal K cells, responsible augmenting insulin release, has gained attention its independent amicable glucagon-like peptide 1 (GLP-1), another L cells. The GIP receptor (GIPR) found in whole adipose tissue, whereas GLP-1 (GLP-1R) not, some studies suggest that GIPR action lowers body weight plays role lipolysis, glucose/lipid uptake/disposal, blood flow, lipid oxidation, free-fatty acid (FFA) re-esterification, which may or not be influenced by other hormones such insulin. This review summarizes research of (distinct depots white brown) using cellular, rodent, human models. In doing so, we explore mechanisms GIPR-based medications treating metabolic disorders, type 2 diabetes obesity, how agonism antagonism contribute to improvements outcomes, potentially through actions tissues.

Язык: Английский

Процитировано

6