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

GLP-1RA and SGLT2i Medications for Type 2 Diabetes and Alzheimer Disease and Related Dementias DOI
Huilin Tang, William T. Donahoo, Steven T. DeKosky

et al.

JAMA Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Importance The association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) risk of Alzheimer disease related dementias (ADRD) remains to be confirmed. Objective To assess the ADRD associated with GLP-1RAs SGLT2is in people type 2 diabetes (T2D). Design, Setting, Participants This target trial emulation study used electronic health record data from OneFlorida+ Clinical Research Consortium January 2014 June 2023. Patients were 50 years or older T2D no prior diagnosis antidementia treatment. Among 396 963 eligible patients T2D, 33 858 included GLP-1RA vs other glucose-lowering drug (GLD) cohort, 34 185 SGLT2i GLD 24 117 cohort. Exposures Initiation treatment a GLP-1RA, SGLT2i, second-line GLD. Main Outcomes Measures was identified using clinical codes. Hazard ratios (HRs) 95% CIs estimated Cox proportional hazard regression models inverse probability weighting (IPTW) adjust for potential confounders. Results cohort (mean age, 65 years; 53.1% female), 65.8 49.3% 63.8 51.7% female). In IPTW-weighted cohorts, incidence rate lower initiators compared (rate difference [RD], −2.26 per 1000 person-years [95% CI, −2.88 −1.64]), yielding an HR 0.67 (95% 0.47-0.96). had than (RD, −3.05 −3.68 −2.42]), 0.57 0.43-0.75). There SGLT2is, RD −0.09 −0.80 0.63) 0.97 0.72-1.32). Conclusion Relevance both statistically significantly decreased GLDs, observed drugs.

Language: Английский

Citations

2
Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism DOI Creative Commons
Yixuan Wang, Hao Hu, Xinyu Liu

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 23, 2023

Alzheimer's Disease (AD) is a global chronic disease in adults with beta-amyloid (Aβ) deposits and hyperphosphorylated tau protein as the pathologic characteristics. Although exact etiology of AD still not fully elucidated, aberrant metabolism including insulin signaling mitochondria dysfunction plays an important role development AD. Binding to receptor substrates, can transport through blood-brain barrier (BBB), thus mediating pathways regulate physiological functions. Impaired pathways, PI3K/Akt/GSK3β MAPK could cause damage brain pathogenesis Mitochondrial overexpression TXNIP also be causative links between DM. Some antidiabetic medicines may have benefits treatment Metformin beneficial for cognition improvement patients, although results from clinical trials were inconsistent. Exendin-4 affect animal models but there lack trials. Liraglutide dulaglutide benefit patients adequate studies semaglutide. Dipeptidyl peptidase IV inhibitors (DPP4is) such saxagliptin, vildagliptin, linagliptin, sitagliptin boost cognitive function models. And SGLT2 empagliflozin dapagliflozin considerably protective against new-onset dementia T2DM patients. Insulin therapy promising some indicated that it increase risk Herbal are helpful neuroprotection brain. For example, polyphenols, alkaloids, glycosides, flavonoids glucose metabolism. Focusing on metabolism, we summarized pharmacological mechanism hypoglycemic drugs herbal medicines. New approaches synthesized would provided More needed produce definite evidence effectiveness medications.

Language: Английский

Citations

36
SGLT2 Inhibitor Use and Risk of Dementia and Parkinson Disease Among Patients With Type 2 Diabetes DOI
Hae‐Kyung Kim, Geert Jan Biessels, Min Yu

et al.

Neurology, Journal Year: 2024, Volume and Issue: 103(8)

Published: Sept. 18, 2024

Despite the mechanistic potential of sodium-glucose cotransporter 2 inhibitor (SGLT2i) to improve neurologic outcomes, efficacy SGLT2i in neurodegenerative disorders among patients with type diabetes is not well established. This population-based cohort study aimed investigate association use risks incident dementia and Parkinson disease (PD) diabetes.

Language: Английский

Citations

17
Pharmacological Approaches Using Diabetic Drugs Repurposed for Alzheimer’s Disease DOI Creative Commons

Muna A. Adem,

Boris Decourt, Marwan N. Sabbagh

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(1), P. 99 - 99

Published: Jan. 3, 2024

Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are chronic, progressive disorders affecting the elderly, which fosters global healthcare concern with growing aging population. Both T2DM AD have been linked increasing age, advanced glycosylation end products, obesity, insulin resistance. Insulin resistance in periphery is significant development of it has posited that brain plays a key role pathogenesis, earning name “type 3 diabetes”. These clinical epidemiological links between become increasingly pronounced throughout years, serve as means to investigate effects antidiabetic therapies AD, such metformin, intranasal insulin, incretins, DPP4 inhibitors, PPAR-γ agonists, SGLT2 inhibitors. The majority these drugs shown benefit preclinical trials, some promising results improvement cognitive faculties participants mild impairment AD. In this review, we summarize benefits, risks, conflicting data currently exist for diabetic being repurposed treatment

Language: Английский

Citations

15
Assessment of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and other antidiabetic agents in Alzheimer’s disease: A population-based study DOI Creative Commons

Mar Garcia-Zamora,

Gemma García‐Lluch, Lucrecia Moreno

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107295 - 107295

Published: July 4, 2024

The lack of effective treatments for dementia has led to explore the potential antidiabetic agents as a possible approach. This cross-sectional and population-based study aimed investigate relationship between each drug their defined daily doses (DDDs) use anti-Alzheimer's disease (AD) drugs in order establish new hypotheses about role AD. For that purpose, database containing information on medications prescribed 233183 patients aged 50 years or older 2018 2020 was used. DDDs were calculated according ATC/DDD index 2023. Statistical analyses, with logistic regression, carried out assess anti-AD consumption. A total 91836 who at least one antihypertensive, antidiabetic, lipid-modifying agent included study; specifically, 29260 medication. Among agents, glucagon-like peptide-1 analogs (GLP-1) likely have positive association people 70 80 years. Additionally, sodium-glucose cotransporter 2 inhibitors (SGLT2i) prone usage across almost every age. However, insulin associated an increased agents. In conclusion, there is evidence suggesting correlation certain dementia. Specifically, GLP-1 SGLT2i might be lower odds usage, while insulins linked higher using drugs.

Language: Английский

Citations

15
SGLT2 inhibitors: a novel therapy for cognitive impairment via multifaceted effects on the nervous system DOI Creative Commons
Jiaqi Mei,

Yi Li,

Liyan Niu

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 9, 2024

The rising prevalence of diabetes mellitus has casted a spotlight on one its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for management, are increasingly studied their benefits. These benefits may include reduction oxidative stress and neuroinflammation, decrease amyloid burdens, enhancement neuronal plasticity, improved cerebral glucose utilization. multifaceted effects the relatively favorable side-effect profile SGLT2 inhibitors render them promising therapeutic candidate disorders. Nonetheless, application impairment is not without limitations, necessitating more comprehensive research to fully determine potential treatment. In this review, we discuss role in neural function, elucidate diabetes-cognition nexus, synthesize current knowledge based animal studies clinical evidence. Research gaps proposed spur further investigation.

Language: Английский

Citations

15
Alzheimer’s Disease as Type 3 Diabetes: Understanding the Link and Implications DOI Open Access
Mateusz Kciuk, Weronika Kruczkowska, Julia Gałęziewska

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11955 - 11955

Published: Nov. 7, 2024

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two prevalent conditions that present considerable public health issue in aging populations worldwide. Recent research has proposed a novel conceptualization of AD as "type 3 diabetes", highlighting the critical roles insulin resistance impaired glucose metabolism pathogenesis disease. This article examines implications this association, exploring potential new avenues for treatment preventive strategies AD. Key evidence linking to emphasizes metabolic processes contribute neurodegeneration, including inflammation, oxidative stress, alterations signaling pathways. By framing within context, we can enhance our understanding its etiology, which turn may influence early diagnosis, plans, measures. Understanding manifestation opens up possibility employing therapeutic incorporate lifestyle modifications use antidiabetic medications mitigate cognitive decline. integrated approach improve patient outcomes deepen comprehension intricate relationship between neurodegenerative diseases disorders.

Language: Английский

Citations

13
Risk of Dementia in Patients with Diabetes Using Sodium-Glucose Transporter 2 Inhibitors (SGLT2i): A Systematic Review, Meta-Analysis, and Meta-Regression DOI Creative Commons
Pricilla Yani Gunawan, Paskalis Andrew Gunawan, Timotius Ivan Hariyanto

et al.

Diabetes Therapy, Journal Year: 2024, Volume and Issue: 15(3), P. 663 - 675

Published: Feb. 10, 2024

Dementia is quite prevalent and among the leading causes of death worldwide. According to earlier research, diabetes may increase possibility developing dementia. However, association between antidiabetic agents dementia not yet clear. This investigation examines use sodium-glucose transporter 2 inhibitors (SGLT2i) risk in patients with diabetes. Up April 18, 2023, four databases—Europe PMC, Medline, Scopus, Cochrane Library—were searched for relevant literature. We included all studies that examine adults who SGLT2i. Random-effect models were used compute outcomes this investigation, producing pooled odds ratios (OR) 95% confidence intervals (CI). Pooled data from seven observational revealed SGLT2i was linked a lower people (OR 0.45, CI 0.34–0.61; p < 0.00001, I2 = 97%). The reduction due SGLT2i's neuroprotective effect only significantly affected by dyslipidemia (p 0.0004), but sample size 0.2954), study duration 0.0908), age 0.0805), sex 0.5058), hypertension 0.0609), cardiovascular disease 0.1619), or stroke 0.2734). taking reduces incidence having beneficial impact. Randomized controlled trials (RCTs) are still required order verify findings our research.

Language: Английский

Citations

12
The impact of sodium‐glucose co‐transporter‐2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation DOI

Yun‐Yu Chen,

Hao‐Chih Chang, Yenn‐Jiang Lin

et al.

Diabetes/Metabolism Research and Reviews, Journal Year: 2024, Volume and Issue: 40(2)

Published: Feb. 1, 2024

Abstract Aims The effectiveness of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i risk diabetic AF, explore interactions oral anticoagulants or dipeptidyl peptidase‐4 (DPP4i). Materials Methods We conducted a cohort using Taiwan's National Health Insurance Research Database. Patients AFwithout prior history established cardiovascular diseases, were identified. Using propensity score matching, 810 receiving matched 1620 not SGLT2i. primary outcome was dementia, secondary outcomes included composite events mortality. Results After up 5 years follow‐up, use associated significantly lower (hazard: 0.71, 95% confidence interval: 0.51–0.98), particularly vascular (HR: 0.44, CI: 0.24–0.82). related reduced risks AF‐related hospitalisation 0.72, 0.56–0.93), stroke 0.75, 0.60–0.94), all‐cause death 0.33, 0.24–0.44). protective effects consistent irrespective concurrent non‐vitamin K antagonist (NOACs) DPP4i. Conclusions In hospitalisation, stroke, death. independent either NOACs

Language: Английский

Citations

11
Association between SGLT2 Inhibitors and Risk of Dementia and Parkinson's Disease: A Meta-Analysis of 12 Randomized Controlled Trials DOI Creative Commons
Vikash Jaiswal, Yusra Mashkoor,

Nishchita Raj

et al.

The American Journal of Medicine, Journal Year: 2024, Volume and Issue: 137(11), P. 1136 - 1141

Published: July 6, 2024

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to reduce the risk of hospitalizations from heart failure and cardiovascular mortality. However, SGLT2i therapy's potential effects on risks dementia Parkinson's disease are not well established, with conflicting results based observational studies. Hence, we sought evaluate association between in patients type diabetes mellitus, failure, or chronic kidney disease.

Language: Английский

Citations

11