Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(1), С. 364 - 364

Опубликована: Янв. 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.

Язык: Английский

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Cognitive dysfunction in diabetes – the ‘forgotten’ diabetes complication: a narrative review

Scandinavian Journal of Primary Health Care, Год журнала: 2025, Номер unknown, С. 1 - 7

Опубликована: Янв. 28, 2025

In addition to peripheral neuropathy of various kinds, diabetes can also cause central neuropathy, which among other things manifest itself as premature cognitive dysfunction, often linked vascular dysfunction. Although the link between and dysfunction was discovered more than 100 years ago has important clinical implications, this complication remains relatively unknown. Recent have seen research that clarified cerebral insulin resistance defective signaling examples pathogenic factors behind impairment in diabetes. We provide a narrative review select contemporary publications with relevance for interface diabetes/prediabetes function. Recently published studies show physical activity reverse brain well pathological appetite regulation. Pharmacological interventions with, example, nasal insulin, GLP-1 receptor agonists, SGLT-2 inhibitors, or PPAR-γ agonists shown promising results. Optimization lifestyle (e.g. activity), several pharmaceutical agents already use against diabetes, results improving function diabetic patients. An task primary health care, where most patients type 2 are diagnosed, treated, followed, is increase awareness early detection these optimizing risk factor control.

Язык: Английский

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Challenges, current innovations, and opportunities for managing type 2 diabetes in frail older adults: a position paper of the European Geriatric Medicine Society (EuGMS)—Special Interest Group in Diabetes

European Geriatric Medicine, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

This position paper aims to address the challenges of managing type 2 diabetes mellitus (T2DM) in frail older adults, a diverse and growing demographic with significant variability health status. The primary research questions are: How can frailty assessment be effectively integrated into care? What strategies optimize glycaemic control outcomes for adults? innovative tools technologies, including artificial intelligence (AI), improve management this population? uses 5 I's framework (Identification, Innovation, Individualization, Integration, Intelligence) integrate care, proposing such as tools, novel therapies, digital AI systems. It also examines metabolic heterogeneity, highlighting anorexic-malnourished sarcopenic-obese phenotypes. proposed highlights importance tailoring targets levels, prioritizing quality life, minimizing treatment burden. Strategies leveraging are emphasized their potential enhance personalized care. distinct needs two phenotypes outlined, specific recommendations each group. calls holistic, patient-centered approach care ensuring equity access innovations life. need fill evidence gaps, refine healthcare integration better vulnerable

Язык: Английский

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Alterations in cerebral perfusion and substrate metabolism in type 2 diabetes: interactions with APOE-ε4

Diabetologia, Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

Язык: Английский

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Sodium‐glucose cotransporter‐2 inhibitors and subtype‐specific dementia risk: A multinational and multiethnic cohort study

Diabetes Obesity and Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Abstract Aims Type 2 diabetes mellitus (T2DM) significantly increases the risk of dementia, including Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia. Although sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) have shown potential neuroprotective effects, previous studies were limited by small sample sizes, single‐country datasets a lack detailed analyses subtypes. Materials Methods This retrospective cohort study utilized TriNetX database, comprising de‐identified electronic health records from over 100 million patients across 98 healthcare organizations worldwide. Adults with T2DM initiating treatment either SGLT2i or dipeptidyl peptidase‐4 (DPP4i) between November 20, 2004, 2024, included. Propensity score matching (PSM) at 1:1 ratio ensured balanced baseline characteristics. Primary outcomes included overall specific subtypes (VaD, AD, other dementias), while secondary all‐cause mortality. Results After propensity matching, 278 689 per group analysed. use was associated lower incidence (2.9% vs. 6.7%; adjusted hazard [AHR] 0.77, 95% confidence interval [CI], 0.75–0.79) (AHR 0.80), 0.82) dementias 0.68). These associations remained consistent age, sex, glycaemic control concurrent medication in subgroup analyses. also linked to mortality (4.1% 11.2%; AHR 0.66, CI, 0.65–0.68). Findings robust sensitivity analyses, supporting effects SGLT2i. Conclusions large‐scale observational suggests that is risks multiple T2DM.

Язык: Английский

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Use of sodium‐glucose cotransporter‐2 inhibitors and risk of dementia: A population‐based cohort study

Diabetes Obesity and Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

The effects of sodium-glucose co-transporter 2 inhibitors (SGLT-2i) on dementia risk have not been assessed in the Chinese population. We aimed to assess association between use SGLT-2i and incidence a mainland A target trial vs. dipeptidyl peptidase 4 (DPP-4i) was emulated, with cohorts type diabetes mellitus patients who were new users or DPP-4i being assembled using Yinzhou Regional Health Care Database. Inverse probability treatment weighting (IPTW) applied control potential confounding, Cox model used estimate hazard ratio (HR) incident dementia. final cohort included 47 335 SGLT-2i. In primary analysis, 500.2 347.5 per 100 000 person-years SGLT-2i, respectively. associated reduced after adjusting for confounding IPTW, an HR 0.74 (95% CI, 0.60-0.93). results generally consistent various subgroup analyses sensitivity analyses. is decreased study population China.

Язык: Английский

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Targeting Ferroptosis in Parkinson’s: Repurposing Diabetes Drugs as a Promising Treatment

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1516 - 1516

Опубликована: Фев. 11, 2025

This review explores the promising potential of repurposing type 2 diabetes (T2D) medications for treatment Parkinson's disease (PD), highlighting shared pathophysiological mechanisms between these two age-related conditions, such as oxidative stress, mitochondrial dysfunction, and ferroptosis. The overlap suggests that existing drugs could target common pathways involved in both conditions. Specifically, discusses how T2D medications, including metformin (Met), peroxisome-proliferator-activated receptor gamma (PPAR-γ) agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, incretins, dipeptidyl-peptidase 4 (DPP-4) can improve function, reduce neuroinflammation potentially inhibit connection ferroptosis treatments, medication, are only beginning to be explored. limited data attributed also complexity fact specific role pathogenesis has not been a primary focus until recent. Despite preclinical evidence, clinical findings mixed, underscoring need further research elucidate drugs' roles neurodegeneration. Repurposing have well-established safety profiles significantly time cost associated with drug development offer more comprehensive approach managing compared treatments targeting single mechanism.

Язык: Английский

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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

Diabetes & Metabolism, Год журнала: 2025, Номер unknown, С. 101623 - 101623

Опубликована: Фев. 1, 2025

Язык: Английский

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Parkinson's disease and glucose metabolism impairment

Translational Neurodegeneration, Год журнала: 2025, Номер 14(1)

Опубликована: Фев. 17, 2025

Abstract Parkinson's disease (PD) is the second most common neurodegenerative disorder. PD patients exhibit varying degrees of abnormal glucose metabolism throughout stages. Abnormal closely linked to pathogenesis and progression. Key processes involved in include transport, glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, pentose phosphate pathway, gluconeogenesis. Recent studies suggest that a potential therapeutic target for PD. In this review, we explore connection between metabolism, focusing on underlying pathophysiological mechanisms. We also summarize drugs related based results from current cellular animal model studies.

Язык: Английский

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Risk of depression and dementia among individuals treated with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists

Current Opinion in Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Purpose of the review To whether sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists decrease risk depression, suicidal ideation cognitive impairment in later life. Recent findings The results studies using information derived from large registries administrative health datasets suggest that GLP-1 (RAs) increase suicidality, although have been inconsistent. One nested-case control study reported SGLT2i decreases depression among adults with diabetes, a small trial empagliflozin provided supportive evidence. Several observational RAs dementia risk, target finding greater benefit associated use compared other medicines commonly used to manage diabetes. Summary RA may effects these on mood not as well explored, but there are concerns about potential increased suicidality users. Prescription bias could explain some associations, so robust evidence is now needed confirm or dismiss findings.

Язык: Английский

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