The pharmacodynamics-based prophylactic benefits of GLP-1 receptor agonists and SGLT2 inhibitors on neurodegenerative diseases: evidence from a network meta-analysis DOI Creative Commons
Ping‐Tao Tseng,

Bing‐Yan Zeng,

Chih-Wei Hsu

et al.

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 6, 2025

Abstract Background Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors represent a new generation of antihyperglycemic agents that operate through mechanisms distinct from conventional diabetes treatments. Beyond their metabolic effects, these medications have demonstrated neuroprotective properties in preclinical studies. While clinical trials explored therapeutic potential established neurodegenerative conditions, role disease prevention remains unclear. We conducted network meta-analysis (NMA) to comprehensively evaluate the prophylactic benefits across multiple diseases identify most promising preventive strategies. Methods systematically searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ProQuest, ScienceDirect, Web Science, ClinicalTrials.gov October 24th, 2024, for randomized controlled (RCTs) GLP-1 or SGLT2 inhibitors. Our primary outcome was incidence seven major diseases: Parkinson’s disease, Alzheimer’s Lewy body dementia, sclerosis, amyotrophic lateral frontotemporal Huntington’s disease. Secondary outcomes included safety profiles assessed dropout rates. performed frequentist-based NMA evaluated risk bias with Risk Bias tool. The main result current study would be re-affirmed via sensitivity test Bayesian-based NMA. Results analysis encompassed 22 RCTs involving 138,282 participants (mean age 64.8 years, 36.4% female). Among all investigated medications, only dapagliflozin significant benefits, specifically preventing (odds ratio = 0.28, 95% confidence intervals 0.09 0.93) compared controls. Neither nor other showed effects any conditions. Drop-out rates were comparable Conclusions This comprehensive reveals novel specific effect against representing breakthrough neurology. specificity dapagliflozin’s protective might rely on its highly selective inhibition SGLT2. These findings provide important direction future research could inform strategies populations at Trial registration PROSPERO CRD42021252381.

Language: Английский

Antidiabetic agents as a novel treatment for Alzheimer’s and Parkinson’s disease DOI Creative Commons

Joseph Nowell,

Eleanor G Blunt, Dhruv Gupta

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 89, P. 101979 - 101979

Published: June 15, 2023

Therapeutic strategies for neurodegenerative disorders have commonly targeted individual aspects of the disease pathogenesis to little success. Neurodegenerative diseases, including Alzheimer's (AD) and Parkinson's (PD), are characterized by several pathological features. In AD PD, there is an abnormal accumulation toxic proteins, increased inflammation, decreased synaptic function, neuronal loss, astrocyte activation, perhaps a state insulin resistance. Epidemiological evidence has revealed link between AD/PD type 2 diabetes mellitus, with these sharing some commonalities. Such opened up promising avenue repurposing antidiabetic agents in treatment disorders. A successful therapeutic strategy would likely require single or which target separate processes disease. Targeting cerebral signalling produces numerous neuroprotective effects preclinical brain models. Clinical trials shown promise approved diabetic compounds improving motor symptoms PD preventing decline, further phase II III underway populations. Alongside signalling, targeting incretin receptors represents one most currently available AD/PD. Most notably, glucagon-like-peptide-1 (GLP-1) receptor agonists displayed impressive clinical potential early studies. GLP-1 agonist, liraglutide, been demonstrated improve glucose metabolism functional connectivity small-scale pilot trials. Whilst agonist exenatide effective restoring function cognition. reduces inhibits apoptosis, prevents protein aggregation, enhances long-term potentiation autophagy as well restores dysfunctional signalling. Support also increasing use additional treatments, intranasal insulin, metformin hydrochloride, peroxisome proliferator-activated nuclear γ agonists, amylin analogs, tyrosine phosphatase 1B inhibitors investigation deployment treatment. As such, we provide comprehensive review anti-diabetic PD.

Language: Английский

Citations

84
Atrial fibrillation: comorbidities, lifestyle, and patient factors DOI Creative Commons
Eduard Shantsila, Eue‐Keun Choi, Deirdre A. Lane

et al.

The Lancet Regional Health - Europe, Journal Year: 2024, Volume and Issue: 37, P. 100784 - 100784

Published: Feb. 1, 2024

Modern anticoagulation therapy has dramatically reduced the risk of stroke and systemic thromboembolism in people with atrial fibrillation (AF). However, AF still impairs quality life, increases heart failure, is linked to cognitive impairment. There also a recognition residual thromboembolic complications despite anticoagulation. Hence, management evolving towards more comprehensive understanding factors predisposing development this arrhythmia, its' interventions mitigate risk. This review summarises recent advances for incident managing these factors. It includes discussion lifestyle, somatic, psychological, socioeconomic The available data call practice shift individualised approach considering an increasingly broader range health patient contributing AF-related burden. highlights needs living co-morbidities (especially multimorbidity), polypharmacy role changing population demographics affecting European region globally.

Language: Английский

Citations

28
Sodium-glucose cotransporter-2 inhibitors and their potential role in dementia onset and cognitive function in patients with diabetes mellitus: a systematic review and meta-analysis DOI Creative Commons

Y J Youn,

Seung Yeon Kim,

Hyun‐Jeong Jeong

et al.

Frontiers in Neuroendocrinology, Journal Year: 2024, Volume and Issue: 73, P. 101131 - 101131

Published: Feb. 16, 2024

This systematic review and meta-analysis aimed to determine the association between use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors dementia onset as well cognitive function in patients with diabetes mellitus. We comprehensively searched MEDLINE, Embase, CENTRAL databases select relevant studies published up August 2023. The SGLT-2 significantly lowers risk compared SGLT-2i non-users (Hazard ratio: 0.68, 95 % CI: 0.50-0.92). Furthermore, our findings indicated a positive effect inhibitor on score improvement, demonstrated by standardized mean difference 0.88 (95 0.32-1.44), particularly among populations mild impairment or dementia. indicate potential role reducing These underscore need for well-controlled large clinical trials future research this field.

Language: Английский

Citations

24
Associations of semaglutide with first‐time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real‐world data in the US DOI Creative Commons
William Yang Wang,

QuangQiu Wang,

Xin Qi

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Abstract INTRODUCTION Emerging preclinical evidence suggests that semaglutide, a glucagon‐like peptide receptor agonist (GLP‐1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration neuroinflammation. However, real‐world its ability to protect Alzheimer's disease (AD) is lacking. METHODS We conducted emulation target trials based on nationwide database of electronic health records (EHRs) 116 million US patients. Seven were emulated among 1,094,761 eligible patients with T2DM who had no prior AD diagnosis by comparing semaglutide seven other antidiabetic medications. First‐ever occurred within 3‐year follow‐up period was examined using Cox proportional hazards Kaplan–Meier survival analyses. RESULTS Semaglutide associated significantly reduced risk first‐time diagnosis, most strongly compared insulin (hazard ratio [HR], 0.33 [95% CI: 0.21 0.51]) weakly GLP‐1RAs (HR, 0.59 0.37 0.95]). Similar results seen across obesity status, gender, age groups. DISCUSSION These findings support further studies assess semaglutide's potential in preventing AD. HIGHLIGHTS 40% 70% risks medications, including GLP‐1RAs. lower AD‐related medication prescriptions. reductions Our provide supporting the clinical benefits mitigating initiation development T2DM. delaying or

Language: Английский

Citations

23
Impact of Sodium Glucose Cotransporter 2 Inhibitors (SGLT2i) Therapy on Dementia and Cognitive Decline DOI Creative Commons

Antonio Lardaro,

L. Quarta,

Stefania Pagnotta

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1750 - 1750

Published: Aug. 3, 2024

Dementia is an age-related syndrome characterized by the progressive deterioration of cognition and capacity for independent living. Diabetes often associated with cognitive decline shares similar pathophysiological mechanisms dementia, such as systemic inflammation, oxidative stress, insulin resistance, advanced glycation end-products formation. Therefore, adequate diabetes management may reduce risk decline, especially in patients other comorbidities factors. The sodium glucose cotransporter inhibitors (SGLT2i) regulate renal reabsorption blocking SGLT2 cotransporters located proximal tubules, causing glycosuria intraglomerular pressure reduction. Their use helps to lower blood modifying water homeostasis; these drugs are also commonly used treatment heart failure chronic kidney disease, while recently, a potential neuroprotective role central nervous system has been suggested. aim our scoping review analyze current evidence about effects SGLT2i adult patients. We performed literature evaluate effect on mild impairment (MCI) Alzheimer's disease incidence progression. screening process was through different searches PubMed EMBASE, evaluating original works published up January 2024. In conclusion, could be diabetes, reducing or progression MCI dementia. Further prospective studies needed validate this hypothesis effectiveness class normal glycemic profile

Language: Английский

Citations

19
Risk of dementia after initiation of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in adults aged 40-69 years with type 2 diabetes: population based cohort study DOI Creative Commons
Anna Shin, Bo Kyung Koo,

Jun Young Lee

et al.

BMJ, Journal Year: 2024, Volume and Issue: unknown, P. e079475 - e079475

Published: Aug. 28, 2024

To compare the risk of dementia associated with sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) in adults aged 40-69 years type 2 diabetes.

Language: Английский

Citations

18
Association between use of sodium-glucose co-transporter-2 inhibitor and the risk of incident dementia: a population-based cohort study DOI Creative Commons
Zarin Abdullah, Ying Cui, Robert W. Platt

et al.

BMJ Open Diabetes Research & Care, Journal Year: 2025, Volume and Issue: 13(1), P. e004541 - e004541

Published: Jan. 1, 2025

Objectives To assess the association between sodium-glucose co-transporter-2 inhibitor (SGLT-2i) use and risk of incident dementia compared with dipeptidyl peptidase-4 inhibitors (DPP-4i) among individuals type 2 diabetes. Design A population-based retrospective cohort study. Setting The Clinical Practice Research Datalink (CPRD) Aurum database from UK. Participants Individuals diabetes, aged 40 years or older, newly prescribed SGLT-2i DPP-4i on after 2013–2021, registered in CPRD database. Main outcome measure primary was dementia, secondary mild cognitive impairment (MCI). Cox proportional hazard models were used to estimate HR corresponding 95% CI for outcomes. Propensity score fine stratification weights adjust confounding. Results Among a 118 006 individuals, rate (IR) 0.56/1000 person-years over median follow-up period 1.54 users 2.67/1000 users, 1.79 years. adjusted 0.78 (95% 0.55 1.12), while MCI 0.86 0.80 0.92). age-specific stratified analysis demonstrated elderly, ≥65 years, 0.50 0.31 0.80). Conclusion Primary findings did not yield conclusive evidence infer an dementia.

Language: Английский

Citations

3
Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Nervous System Disorders: A Systematic Review and Meta-Analysis DOI
Bo Xu,

Mingxia Yang,

Shaoqian Li

et al.

Annals of Pharmacotherapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 23, 2025

Background: Adults with type 2 diabetes mellitus (T2DM) are at an increased risk for certain brain or psychiatric disorders, as those without chronic kidney disease heart failure. Whether sodium-glucose cotransporter (SGLT2) inhibitors associated these diseases is unclear. Objective: This systematic review and meta-analysis aimed to investigate the effects of SGLT2 on nervous system disorders. Methods: We searched PubMed, ClinicalTrials.gov, Web Science randomized, double-blind placebo-controlled trials least ≥24 weeks. used Mantel–Haenszel statistical method, ratio (RR), 95% confidence interval (CI) dichotomous variables. Results: included 52 publications/trials covering 111 376 participants (SGLT2 62 192; Placebo 49 184). Sodium-glucose had no significant effect ischaemic stroke (RR = 0.97; CI 0.87-1.09; P 0.64), cerebrovascular accident 1.05; 0.91-1.22; 0.50), dementia 1.29; 0.78-2.12; 0.32), carotid artery occlusion/carotid stenosis 1.18; CI: 0.92-1.53; 0.20), haemorrhagic 0.84; 0.62-1.12; 0.23), transient attack 0.82-1.15; 0.73) compared placebo. No heterogeneity was observed. However, showed slight reduce Parkinson’s (major failure subgroup). Empagliflozin dapagliflozin significantly syncope 1.65; 1.15-2.38; < 0.01) 1.04-2.61; 0.03), respectively. Conclusion Relevance: disorders There reduced Disease observed in some specific populations. In addition, risks empagliflozin concerning worth attention.

Language: Английский

Citations

3
Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits DOI Open Access
Joyce Yip, Grace Shu Hui Chiang,

I Lee

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 364 - 364

Published: Jan. 3, 2025

This review describes our current understanding of the role mitochondria in repurposing anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, obesity. Metformin, most prominent these diabetes drugs, has been called “Drug Miracles Wonders,” as trials have found it to be beneficial human patients suffering from maladies. To promote viral replication all infected cells, SARS-CoV-2 stimulates liver cells produce glucose export into blood stream, which can cause COVID patients, reduces levels blood, was shown cut incidence rate half recovering SARS-CoV-2. Metformin leads phosphorylation AMP-activated protein kinase AMPK, accelerates import via transporter GLUT4 switches starvation mode, counteracting virus. Diabetes also stimulate unfolded response thus mitophagy, is healthy aging health. were mimic exercise help reduce body weight.

Language: Английский

Citations

2
Comparative Effectiveness of SGLT2 Inhibitors and GLP-1 Receptor Agonists in Preventing Alzheimer's Disease, Vascular Dementia, and Other Dementia Types Among Patients with Type 2 Diabetes DOI
Mingyang Sun, Xiaoling Wang, Zhongyuan Lu

et al.

Diabetes & Metabolism, Journal Year: 2025, Volume and Issue: unknown, P. 101623 - 101623

Published: Feb. 1, 2025

Language: Английский

Citations

2