Comparative efficacy and safety of antidiabetic agents in Alzheimer's disease: A network meta-analysis of randomized controlled trials DOI Creative Commons
Zixin Cai, Jiaxin Zhong, Guanghui Zhu

и другие.

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2025, Номер unknown, С. 100111 - 100111

Опубликована: Фев. 1, 2025

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options. Emerging evidence suggests that antidiabetic agents may offer neuroprotective effects by targeting shared pathophysiological mechanisms such as insulin resistance and neuroinflammation. However, the comparative efficacy, safety of these in AD remain unclear. This study aimed to systematically evaluate compare efficacy for improving cognitive outcomes, reducing amyloid-β (Aβ) deposition, managing adverse patients AD, using network meta-analysis randomized controlled trials (RCTs). A comprehensive literature search was conducted across multiple databases identify RCTs examining AD. The primary outcomes included performance (e.g., MMSE scores), Aβ deposition (measured via CSF biomarkers), safety/adverse effects. performed integrate direct indirect evidence, ranking interventions Surface Under Cumulative Ranking (SUCRA) probabilities. Risk bias assessed Cochrane risk-of-bias tool. total 26 studies, involving 7,361 participants, were analysis. evaluated detemir (both low-dose high-dose), liraglutide, exenatide, metformin, pioglitazone. Both (mean difference: 2.10, 95 % CI: 1.04 3.15), high-dose 1.40, -0.07 2.88), exenatide 1.19, 0.06 2.32), metformin combined 1.06, -1.68 3.80) showed improvements compared placebo. Among these, demonstrated most significant improvement. In terms ranked highest effectiveness, SUCRA score (84.6), followed (SUCRA: 54.1). Low-dose 51.1) also moderate efficacy. some reduction -0.31, -2.82 2.20), although statistical significance limited. Liraglutide exhibited rate withdrawal 1.97, 4.00), while pioglitazone lowest rates 0.07, -0.03 0.17). provides valuable insights into improvement effect on deposition. Metformin emerged effective agent levels, though its function less pronounced. Safety profiles varied, liraglutide associated withdrawals, incidence treatment-related discontinuations. These findings support potential use agents, particularly detemir, therapeutic option further studies are needed confirm their long-term benefits safety.

Язык: Английский

Glucagon-like peptide-1 receptor: mechanisms and advances in therapy DOI Creative Commons

Zhikai Zheng,

Zong Yao,

Yiyang Ma

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 18, 2024

The glucagon-like peptide-1 (GLP-1) receptor, known as GLP-1R, is a vital component of the G protein-coupled receptor (GPCR) family and found primarily on surfaces various cell types within human body. This specifically interacts with GLP-1, key hormone that plays an integral role in regulating blood glucose levels, lipid metabolism, several other crucial biological functions. In recent years, GLP-1 medications have become focal point medical community due to their innovative treatment mechanisms, significant therapeutic efficacy, broad development prospects. article thoroughly traces developmental milestones drugs, from initial discovery clinical application, detailing evolution diverse along distinct pharmacological properties. Additionally, this paper explores potential applications agonists (GLP-1RAs) fields such neuroprotection, anti-infection measures, reduction inflammation, enhancement cardiovascular function. It provides in-depth assessment effectiveness GLP-1RAs across multiple body systems-including nervous, cardiovascular, musculoskeletal, digestive systems. includes integrating latest trial data delving into signaling pathways mechanisms. primary goal emphasize extensive benefits using treating spectrum diseases, obesity, non-alcoholic fatty liver disease (NAFLD), neurodegenerative musculoskeletal forms cancer. ongoing new indications for drugs offers promising prospects further expanding interventions, showcasing field.

Язык: Английский

Процитировано

140
Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment DOI Creative Commons
Katherine O. Kopp, Elliot J. Glotfelty, Yazhou Li

и другие.

Pharmacological Research, Год журнала: 2022, Номер 186, С. 106550 - 106550

Опубликована: Ноя. 11, 2022

Chronic, excessive neuroinflammation is a key feature of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's (PD). However, neuroinflammatory pathways have yet to be effectively targeted in clinical treatments for diseases. Interestingly, increased inflammation risk been associated with type 2 diabetes mellitus (T2DM) insulin resistance (IR), suggesting that mitigate T2DM pathology may successful treating well. Glucagon-like peptide-1 (GLP-1) an incretin hormone promotes healthy signaling, regulates blood sugar levels, suppresses appetite. Consequently, numerous GLP-1 receptor (GLP-1R) stimulating drugs developed approved by the US Food Drug Administration (FDA) related global regulatory authorities treatment T2DM. Furthermore, GLP-1R anti-inflammatory, neurotrophic, neuroprotective properties disorder preclinical models, hence hold promise repurposing In this review, we discuss pathways, intersections between neuroinflammation, brain IR, diseases, focus on AD PD. We additionally overview current FDA-approved agents development, including unimolecular single, dual, triple agonists, highlight those trials treatment. propose already-approved agonists safe, efficacious, cost-effective strategy ameliorating PD quelling neuroinflammation.

Язык: Английский

Процитировано

130
The expanding incretin universe: from basic biology to clinical translation DOI Open Access
Daniel J. Drucker, Jens J. Holst

Diabetologia, Год журнала: 2023, Номер 66(10), С. 1765 - 1779

Опубликована: Март 28, 2023

Язык: Английский

Процитировано

128
The amyloid cascade hypothesis: an updated critical review DOI
Kasper P. Kepp,

Nikolaos K. Robakis,

Poul Flemming Høilund‐Carlsen

и другие.

Brain, Год журнала: 2023, Номер 146(10), С. 3969 - 3990

Опубликована: Май 15, 2023

Results from recent clinical trials of antibodies that target amyloid-β (Aβ) for Alzheimer's disease have created excitement and been heralded as corroboration the amyloid cascade hypothesis. However, while Aβ may contribute to disease, genetic, clinical, imaging biochemical data suggest a more complex aetiology. Here we review history weaknesses hypothesis in view new evidence obtained anti-amyloid antibodies. These indicate treatments either no or uncertain effect on cognition. Despite importance definition argue point playing minor aetiological role. We also discuss suggesting concerted activity many pathogenic factors propose evolving multi-factor models will better underpin search effective strategies treat disease.

Язык: Английский

Процитировано

125
Mitochondrial dysfunction in Parkinson’s disease – a key disease hallmark with therapeutic potential DOI Creative Commons
Martin T. Henrich, Wolfgang H. Oertel, D. James Surmeier

и другие.

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Ноя. 11, 2023

Abstract Mitochondrial dysfunction is strongly implicated in the etiology of idiopathic and genetic Parkinson’s disease (PD). However, strategies aimed at ameliorating mitochondrial dysfunction, including antioxidants, antidiabetic drugs, iron chelators, have failed disease-modification clinical trials. In this review, we summarize cellular determinants impairment electron transport chain complex 1, increased oxidative stress, disturbed quality control mechanisms, bioenergetic deficiency. addition, outline pathways to neurodegeneration current context PD pathogenesis, review past treatment an attempt better understand why translational efforts thus far been unsuccessful.

Язык: Английский

Процитировано

106
Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide DOI

Jimena Tatiana Hathaway,

Madhura Shah, David Hathaway

и другие.

JAMA Ophthalmology, Год журнала: 2024, Номер 142(8), С. 732 - 732

Опубликована: Июль 3, 2024

Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated nonarteritic anterior ischemic optic neuropathy (NAION).

Язык: Английский

Процитировано

89
The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS) DOI
Roger S. McIntyre, Rodrigo B. Mansur, Joshua D. Rosenblat

и другие.

Expert Opinion on Drug Safety, Год журнала: 2023, Номер 23(1), С. 47 - 55

Опубликована: Дек. 13, 2023

Recently, the European Medicines Agency (EMA) received reports of suicidal thoughts and self-injury associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) liraglutide semaglutide.

Язык: Английский

Процитировано

66
Understanding the Gut–Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders DOI Open Access
Yadong Zheng, Laura Bonfili, Tao Wei

и другие.

Nutrients, Год журнала: 2023, Номер 15(21), С. 4631 - 4631

Опубликована: Окт. 31, 2023

The gut–brain axis (GBA) is a complex bidirectional communication network connecting the gut and brain. It involves neural, immune, endocrine pathways between gastrointestinal (GI) tract central nervous system (CNS). Perturbations of GBA have been reported in many neurodegenerative disorders (NDDs), such as Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS), among others, suggesting possible role pathogenesis. microbiota pivotal component GBA, alterations its composition, known dysbiosis, associated with dysfunction neurodegeneration. might influence homeostasis CNS by modulating immune and, more directly, regulating production molecules metabolites that systems, making it potential therapeutic target. Preclinical trials manipulating microbial composition through dietary intervention, probiotic prebiotic supplementation, fecal transplantation (FMT) provided promising outcomes. However, clear mechanism not well understood, results are always consistent. Here, we provide an overview major components approaches targeting to ameliorate NDDs.

Язык: Английский

Процитировано

51
Semaglutide ameliorates cognition and glucose metabolism dysfunction in the 3xTg mouse model of Alzheimer's disease via the GLP-1R/SIRT1/GLUT4 pathway DOI
Zhaojun Wang,

Xinru Li,

Shi-Fan Chai

и другие.

Neuropharmacology, Год журнала: 2023, Номер 240, С. 109716 - 109716

Опубликована: Сен. 18, 2023

Язык: Английский

Процитировано

49
Glucagon-like peptide-1 class drugs show clear protective effects in Parkinson's and Alzheimer's disease clinical trials: A revolution in the making? DOI Creative Commons
Christian Hölscher

Neuropharmacology, Год журнала: 2024, Номер 253, С. 109952 - 109952

Опубликована: Апрель 25, 2024

Parkinson's disease (PD) is a complex syndrome for which there no disease-modifying treatment on the market. However, group of drugs from Glucagon-like peptide-1 (GLP-1) class have shown impressive improvements in clinical phase II trials. Exendin-4 (Bydureon), Liraglutide (Victoza, Saxenda) and Lixisenatide (Adlyxin), that are market as treatments diabetes, clear effects improving motor activity patients with PD In addition, has improvement cognition brain shrinkage trial Alzheimer (AD). Two III trials testing GLP-1 drug semaglutide (Wegovy, Ozempic, Rybelsus) ongoing. This perspective article will summarize results obtained so far this novel research area. We at crossroads where emerging new strategy AD. Newer been designed to enter easier being developed already show improved preclinical studies compared older had treat diabetes. The future looks bright AD PD.

Язык: Английский

Процитировано

28