A Brief Review of Incretin Mimetics Intended for the Management of Diabetes and Associated Comorbidities DOI Open Access

Faryal Haider,

Syed Sarim Imam,

Orien L. Tulp

et al.

Published: May 21, 2024

Abstract Incretin mimetics, also known as glucagon-like peptide-1 (GLP-1) receptor agonists, are a class of medications used to treat type 2 diabetes by mimicking the actions incretin hormones in body. These responsible for promoting insulin release from pancreas response nutrient intake, well decreasing glucagon secretion, slowing gastric emptying, and satiety. By imitating these actions, mimetics help regulate blood sugar levels individuals with glucose intolerance. One key benefits is its ability lower without causing hypoglycemia. This especially important who may experience dangerous drops when using other medications. Additionally, have been shown promote weight loss some individuals, making them valuable option those struggling obesity addition diabetes. administered injection, once or twice daily, depending on specific medication. They often combined medications, such metformin insulin, optimal control. generally well-tolerated, common side effects including nausea, vomiting, diarrhea, which usually diminish over time body adjusts Studies that can improve cardiovascular outcomes diabetes, reducing risk heart attacks strokes. particularly significant given increased disease preserve pancreatic beta-cell function, producing insulin. slow progression reduce need higher doses time. Despite their many benefits, not limitations. be expensive compared make less accessible individuals. there concerns about potential pancreatitis cancer associated use However, more research needed fully understand risks. It healthcare providers carefully assess each individual's unique needs medical history considering mimetics. appropriate everyone, cancer. Patients should educated medications' proper administration ensure safety efficacy. Overall, emerged an therapeutic offering mechanism action control, loss, risk. With ongoing development this field, continue show promise tools managing complications comorbidities.

Language: 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

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

16
Managing insulin resistance: the forgotten pathophysiological component of type 2 diabetes DOI

Muhammad Abdul-Ghani,

Pietro Maffei, Ralph A. DeFronzo

et al.

The Lancet Diabetes & Endocrinology, Journal Year: 2024, Volume and Issue: 12(9), P. 674 - 680

Published: Aug. 1, 2024

Language: Английский

Citations

15
Recent advances in peptide-based therapies for obesity and type 2 diabetes DOI Creative Commons
Clifford J. Bailey, Peter R. Flatt, J. Michael Conlon

et al.

Peptides, Journal Year: 2024, Volume and Issue: 173, P. 171149 - 171149

Published: Jan. 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.

Language: Английский

Citations

11
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

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1320 - 1320

Published: June 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

Language: Английский

Citations

11
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

et al.

Peptides, Journal Year: 2025, Volume and Issue: 187, P. 171380 - 171380

Published: March 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).

Language: Английский

Citations

1
Enteroendocrine cell regulation of the gut-brain axis DOI Creative Commons
Joshua R. Barton, Anne Londregan, Tyler D. Alexander

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Nov. 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.

Language: Английский

Citations

19
Non-canonical G protein signaling DOI Creative Commons
Bernd Nürnberg, Sandra Beer‐Hammer, Ellen Reisinger

et al.

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 255, P. 108589 - 108589

Published: Jan. 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.

Language: Английский

Citations

8
Emerging role of antidiabetic drugs in cardiorenal protection DOI Creative Commons

Wen-Jia Fu,

Jin-Ling Huo,

Zi‐Hui Mao

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 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.

Language: Английский

Citations

7
Obesity and the gut microbiota: implications of neuroendocrine and immune signaling DOI Creative Commons
Marina Romaní‐Pérez, Rebeca Liébana-García,

Alejandra Flor‐Duro

et al.

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 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

Language: Английский

Citations

6
The interplay of glucose-dependent insulinotropic polypeptide in adipose tissue DOI Creative Commons

Samrin Kagdi,

Sulayman A. Lyons, Jacqueline L. Beaudry

et al.

Journal of Endocrinology, Journal Year: 2024, Volume and Issue: 261(3)

Published: April 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.

Language: Английский

Citations

6