Glucose-dependent insulinotropic polypeptide (GIP)

Molecular Metabolism, Journal Year: 2025, Volume and Issue: 95, P. 102118 - 102118

Published: Feb. 28, 2025

Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin identified and plays an essential role in maintenance of glucose tolerance healthy humans. Until recently GIP had not been developed as a therapeutic thus has overshadowed by other incretin, glucagon-like peptide 1 (GLP-1), which is basis for several successful drugs to treat diabetes obesity. However, there rekindling interest biology recent years, great part due pharmacology demonstrating that both GIPR agonism antagonism may be beneficial treating obesity diabetes. This apparent paradox reinvigorated field, led new lines investigation, deeper understanding GIP. In this review, we provide detailed overview on multifaceted nature discuss implications signal modification various diseases. Following its classification hormone, emerged pleiotropic hormone with variety metabolic effects outside endocrine pancreas. The numerous render interesting candidate development pharmacotherapies obesity, diabetes, drug-induced nausea bone neurodegenerative disorders.

Language: Английский

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Comparative efficacy of incretin drugs on glycemic control, body weight, and blood pressure in adults with overweight or obesity and with/without type 2 diabetes: a systematic review and network meta-analysis

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 4, 2025

Background The rapid development of multi-receptor drugs targeting glucagon-like peptide-1 receptor (GLP-1R) is driving significant advancements in the treatment individuals with type 2 diabetes and obesity. This systematic review network meta-analysis aims to compare efficacy safety adults overweight or obesity, without diabetes. Methods A search was conducted PubMed, Cochrane, Web Science, Embase, CNKI, WanFang databases up May 12, 2024. Randomized controlled trials (RCTs) an intervention duration at least 12 weeks were included. population interest consisted Eligible studies compared placebo other drugs. primary outcomes weight reduction, glycated hemoglobin (HbA 1c ), fasting plasma glucose (FPG), blood pressure changes, adverse events. Risk bias assessed using version Cochrane risk-of-bias tool (ROB2), a random-effects performed frequentist approach. Confidence effect estimates evaluated In Network Meta-Analysis (CINeMA) framework. Results total 24 trials, involving 9165 participants, Retatrutide (mean difference (MD): -11.91 kg, 95% CI: -19.00 -4.82, P-score: 0.80, p: 0.0003) Tirzepatide (MD: -12.78 -16.10 -9.46, 0.89, p < 0.0001) exhibited superior reducing body weight, all agents except Mazdutide -5.31 -9.78 -0.84, 0.37, 0.0189) achieving reductions over 8 kg. patients diabetes, reduced HbA by 1%, -1.87%, -2.15 -1.59, 0.87, -1.89%, -2.43 -1.35, 0.88, showing greatest effects on glycemic control. For management, significantly systolic -6.69 mmHg, -7.62 -5.75, 0.84, diastolic -3.73 -4.75 -2.71, 0.92, 0.0001), nearly lowering more than 5 mmHg. Non-diabetic participants showed pronounced improvements both pressure. Safety analysis revealed that had favorable profile no impact serious events placebo. Conclusions Multi-receptor demonstrated substantial therapeutic potential control, regulation generally profile. Systematic registration https://www.crd.york.ac.uk/prospero/ , identifier CRD42024554005.

Language: Английский

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The GLP-1 medicines semaglutide and tirzepatide do not alter disease-related pathology, behaviour or cognitive function in 5XFAD and APP/PS1 mice

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 89, P. 102019 - 102019

Published: Aug. 30, 2024

The development of glucagon-like peptide-1 receptor (GLP-1R) agonists for the treatment type 2 diabetes and obesity has been accompanied by evidence anti-inflammatory cytoprotective actions in heart, blood vessels, kidney, brain. Whether GLP-1R might be useful clinically attenuating deterioration cognitive dysfunction reducing progression Alzheimer's disease remains uncertain. Here we evaluated semaglutide tirzepatide, distinct GLP-1 medicines, two mouse models neurodegeneration. Semaglutide reduced body weight improved glucose tolerance 12-month-old male female 5XFAD APP/PS1 mice, consistent with pharmacological engagement GLP-1R. Nevertheless, amyloid plaque density was not different cerebral cortex, hippocampus, or subiculum semaglutide-treated mice. IBA1 GFAP expression were increased hippocampus mice but semaglutide. Moreover, parameters neurobehavioral function using Open Field testing Morris water maze following To explore whether incretin therapies more effective younger studied tirzepatide action 6-month-old Neither nor modified extent accumulation, hippocampal IBA1+ GFAP+ cells, testing, despite improving weight. mRNA biomarkers inflammation neurodegeneration after tirzepatide. Collectively, these findings reveal preservation metabolic yet inability to detect improvement structural functional disease.

Language: Английский

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Dipeptidyl peptidase-4 inhibitors enhance memory retention via neuropeptide Y

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177556 - 177556

Published: March 1, 2025

Language: Английский

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Tirzepatide: A dual action approach to weight reduction and glycemic control in type 2 diabetes mellitus

MGM Journal of Medical Sciences, Journal Year: 2025, Volume and Issue: 12(1), P. 136 - 146

Published: Jan. 1, 2025

Abstract Tirzepatide, a dual GIP and GLP-1 receptor agonist, is an innovative therapy for type 2 diabetes mellitus (T2DM) obesity. By stimulating insulin secretion, inhibiting glucagon release, slowing gastric emptying, enhancing satiety, it offers superior glycemic control weight reduction compared to conventional agonists. Clinical trials, such as SURPASS SURMOUNT, have demonstrated their effectiveness in lowering HbA1c body weight, with potential benefits conditions like NAFLD, PCOS, cardiovascular health. While its therapeutic profile promising, further research needed assess long-term safety, particularly concerning outcomes, gastrointestinal effects, the risk of medullary thyroid carcinoma (MTC). Its once-weekly administration improves adherence; however, cost accessibility remain significant challenges. A personalized medicine approach, incorporating biomarker-driven patient selection, may enhance treatment outcomes. As continues, tripeptide has revolutionize metabolic disease management. Future studies will clarify cost-effectiveness, broader clinical applications.

Language: Английский

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Incretin-based therapeutics for the treatment of neurodegenerative diseases

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Language: Английский

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Role of Glucagon-Like Peptide-1 on Amyloid, Tau, and α-Synuclein: Target Engagement and Rationale for the Development in Neurodegenerative Disorders

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 106159 - 106159

Published: April 1, 2025

Language: Английский

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Tirzepatide for overweight and obesity management

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 19

Published: Dec. 4, 2024

Introduction Tirzepatide is a once-weekly dual agonist, acting on glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. It approved at the same doses (5, 10 15 mg) for both type 2 diabetes (T2D) chronic weight management.

Language: Английский

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