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Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors have potential beneficial effects in Alzheimer's disease (AD).
Methods: We conducted pharmacoepidemiologic studies using two large-scale real-world databases. We fitted covariate-adjusted Cox models to compare the risks of AD among initiators of GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors.
Results: We identified GLP-1 receptor agonist initiation compared to DPP-4 inhibitors initiation was associated with a reduced risk of AD (hazard ratio [HR] ≤ 0.69 and P value < 0.001) and SGLT-2 inhibitor initiation compared to DPP-4 inhibitor initiation was associated with a reduced risk of AD (HR ≤ 0.67 and P value < 0.001).
Discussion: GLP-1 receptor agonist initiation and SGLT-2 inhibitor initiation are associated with a reduced risk of AD. Randomized clinical trials are warranted to validate the causal beneficial effects of GLP-1 receptor agonists and SGLT-2 inhibitors in AD.
Highlights: Glucagon-like peptide-1 (GLP-1) receptor agonists are significantly associated with a reduced risk of Alzheimer's disease (AD) compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are significantly associated with a reduced risk of AD compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Two GLP-1 receptor agonists (liraglutide and semaglutide) and three SGLT-2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) are associated with a reduced risk of AD in drug-specific sensitivity analyses.
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http://dx.doi.org/10.1002/alz.70639 | DOI Listing |
Redox Biol
September 2025
Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong First People's Hospital, Medical School of Nantong University, Nantong, Jiangsu, 226000, China; Research Institute for Spine and Spinal Cord Disease of Nantong University, Nantong, Jiangsu, 226000, China. Elec
Spinal cord injury (SCI) is a devastating condition characterized by the accumulation of myelin debris (MD), persistent neuroinflammation, and impaired neural regeneration. Although macrophages are pivotal for MD clearance, the impact of excessive MD phagocytosis on macrophage phenotype and function remains poorly understood. Building upon our prior evidence that exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, mitigates microglia-driven neuroinflammation post-SCI, this study elucidates the therapeutic efficacy and underlying mechanisms of Ex-4 in alleviating macrophage senescence, restoring efferocytotic capacity, and facilitating neural repair.
View Article and Find Full Text PDFInjury
September 2025
Washington University School of Medicine, Department of Orthopaedic Surgery, St. Louis, MO, USA. Electronic address:
Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for Type 2 diabetes and obesity due to their cardiometabolic benefits. However, their effects on fracture healing remain controversial. This study investigates perioperative GLP-1 RA use and outcomes following surgical treatment of lower extremity (LE) fractures.
View Article and Find Full Text PDFDiabetes Metab Res Rev
September 2025
Department of Nephrology, Daping Hospital, Army Medical University, Chongqing, China.
Chronic kidney disease (CKD) substantially increases cardiovascular risk, with endothelial dysfunction as its central pathological mechanism. This review summarises the molecular regulatory mechanisms underlying endothelial dysfunction in CKD and highlights recent advances in treatment strategies. The pathophysiology of endothelial injuries involves a complex network of multiple factors and mechanisms, including oxidative stress, inflammation, glycocalyx damage, ischaemia, hypoxia, cellular senescence and endothelial-mesenchymal transition (EndMT).
View Article and Find Full Text PDFDiabetes Metab Res Rev
September 2025
Interdisciplinary Department of Medicine, School of Medicine, University of Bari 'Aldo Moro', Bari, Italy.
Overweight and obesity represent common chronic metabolic disorders in the general population, and observed trends describe a substantial growth in the prevalence of weight excess also among individuals with type 1 diabetes (T1D), the so-called 'lean phenotype' of diabetes. The sharp rise of weight excess and obesity-related cardio-nephron-metabolic burdens observed in T2D is expected to produce similar consequences in T1D, leading to the urgent need to endorse therapeutic protocols as in most parts of the World no adjunctive treatments are approved for T1D, making weight excess management challenging in these individuals. The notable results shown by newer glucagon-like peptide 1 receptor agonists (GLP-1RAs) and emerging dual agonists, especially while managing cardio-metabolic burdens, in T2D have encouraged fervent anecdotal and non-anecdotal research also in T1D, indicating that non-insulin injective agents can be effective and safe.
View Article and Find Full Text PDFDrug Deliv Transl Res
September 2025
Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Vidya Vihar, Pilani, Rajasthan, 333031, India.
Diabetes is a metabolic disorder of increasing global concern. Characterized by constantly elevated levels of glucose, severe β-cell dysfunction, and insulin resistance, it is the cause of a major burden on patients if not managed with therapeutic and lifestyle changes. The human body is slowly developing tolerance to many marketed antidiabetic drugs and the quest for the discovery of newer molecules continues.
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