The pharmacodynamics-based prophylactic benefits of GLP-1 receptor agonists and SGLT2 inhibitors on neurodegenerative diseases: evidence from a network meta-analysis

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

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Rock inhibitors in Alzheimer’s disease

Frontiers in Aging, Journal Year: 2025, Volume and Issue: 6

Published: March 20, 2025

Alzheimer’s disease (AD) is the most common age-related neurodegenerative and cause of dementia. AD pathology primarily involves formation amyloid β (Aβ) plaques neurofibrillary tangles containing hyperphosphorylated tau (p-tau). While Aβ targeted treatments have shown clinical promise, other aspects such as microgliosis, astrocytosis, synaptic loss, hypometabolism may be viable targets for treatment. Among notable novel therapeutic approaches, Ras homolog (Rho)-associated kinases (ROCKs) are being investigated treatment, based on observations that ROCK1/2 levels elevated in AD, activation or inhibition ROCKs changes dendritic/synaptic structures, protein aggregate accumulation, inflammation, gliosis. This review will highlight key findings effects ROCK ptau pathologies, well its neuroinflammation, density, potentially metabolism bioenergetics.

Language: Английский

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Glucagon-like peptide-1 receptor agonists for major neurocognitive disorders

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. jnnp - 335593

Published: April 10, 2025

Disease-modifying treatments for major neurocognitive disorders, including Alzheimer’s disease, Parkinson’s disease and other cognitive deficits, are among the main unmet needs in modern medicine. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), currently licensed treatment of type 2 diabetes mellitus obesity, offer a novel, multilayered mechanism intervention neurodegeneration through intermediate, aetiology-agnostic pathways, likely involving metabolic, inflammatory several relevant neurobiological processes. In vitro animal studies have revealed promising signals neuroprotection, with preliminary supportive evidence emerging from recent pharmacoepidemiological investigations clinical trials. this article, we comprehensively review that investigate impact GLP-1RAs on various aetiologies impairment dementia syndromes. Focusing human studies, highlight how brain energy homeostasis, neurogenesis, synaptic functioning, neuroinflammation cellular stress responses, pathological protein aggregates, proteostasis, cerebrovascular system blood-brain barrier dynamics may underlie GLP-1RA putative neuroprotective effects. We then report appraise observational investigations, trials pooled analyses. Finally, discuss current challenges perspectives ahead research implementation care people their individual penetrance potential, need response biomarkers stage-based indications, possible non-specific effects health, profile terms adverse events unwanted effects, lack long-term data efficacy safety, issues surrounding cost availability treatment.

Language: Английский

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GLP-1 Agonists for Weight Loss and Beyond

Transformative Medicine, Journal Year: 2024, Volume and Issue: 3(4), P. 143 - 146

Published: Dec. 19, 2024

Glucagon-like peptide-1 (GLP-1) agonists are medications that were originally approved for type 2 diabetes to help improve glycemic control in conjunction with exercise and dieting. One of the beneficial effects this medication class is weight loss, recently FDA has a select few indication loss. With these becoming increasingly more popular, it imperative both providers patients understand differences terms efficacy potential adverse events make best decision about initiating therapy. This article summarizes indications all GLP-1 includes supporting trial data showcasing their as loss treatments. Outside diabetes, there also may be other benefits seen agonist usage specific populations such cardiovascular disease, neurodegenerative diseases, non-alcoholic fatty liver steatohepatitis.

Language: Английский

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