Pioglitazone for the treatment of Alzheimer’s disease
Abstract
INTRODUCTION: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Pharmacological treatment of AD includes Anticholinesterase Inhibitors (AChEIs) for mild-moderate AD, and memantine for severe AD. These drugs provide mainly symptomatic short-term benefits without clearly influencing the progression of the disease. Pioglitazone (AD4833) is an insulin sensitizer of the thiazolidinedione class of nuclear Peroxisome-Proliferator Activated Receptor γ (PPARγ) agonists. It binds to PPARγ, affecting gene transcription and reducing inflammation. Areas covered: This review discusses the history of Pioglitazone, its pharmacokinetics and pharmacodynamics profile, and safety issues, together with an overview of clinical trials carried out so far. A literature search was made in Pubmed for pioglitazone, AD, trial, and on the ClinicalTrials.gov site for clinical trials with Pioglitazone. Expert opinion: A Phase II study in AD, and its previous indication for diabetes, showed that Pioglitazone is safe and well tolerated. So far, two large Phase III trials are ongoing, but there are no preliminary results yet on a possible beneficial effect on cognition in patients with AD.
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In 2018, two phase 3 clinical trials involving azeliragon for patients with mild Alzheimer's disease were initiated.
“In the year 2018, two phase 3 clinical trials involving azeliragon for patients with mild AD were initiated and its the study (phase 3) in individuals with AD and poor glucose tolerance started in the year 2019 which is expected to be completed in 2023 (Galimberti et al., 2017).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Galimberti et al., 2017
A phase 3 study of azeliragon in individuals with Alzheimer's disease and poor glucose tolerance started in 2019 and is expected to be completed in 2023.
“In the year 2018, two phase 3 clinical trials involving azeliragon for patients with mild AD were initiated and its the study (phase 3) in individuals with AD and poor glucose tolerance started in the year 2019 which is expected to be completed in 2023 (Galimberti et al., 2017).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Galimberti et al., 2017
Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Epidemiology of Alzheimer disease
Reitz, C., Brayne, C., & Mayeux, R. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.2 · Cited by 1,675 · see citing works
Heneka, M. T., Sastre, M., Dumitrescu-Ozimek, L., Hanke, A., Dewachter, I., Kuiperi, C., O'Banion, K., Klockgether, T., Van Leuven, F., & Landreth, G. E. (2005) · Brain · doi:10.1093/brain/awh452 · Cited by 565 · see citing works
How does diabetes accelerate Alzheimer disease pathology?
Sims-Robinson, C., Kim, B., Rosko, A., & Feldman, E. L. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.130 · Cited by 492 · see citing works
Alzheimer disease therapy—moving from amyloid-β to tau
Giacobini, E., & Gold, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.223 · Cited by 483 · see citing works
Yan, Q., Zhang, J., Liu, H., Babu-Khan, S., Vassar, R., Biere, A. L., Citron, M., & Landreth, G. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-20-07504.2003 · Cited by 469 · see citing works
Neuropsychiatric Manifestations in Mild Cognitive Impairment: A Systematic Review of the Literature
Apostolova, L. G., & Cummings, J. L. (2007) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000112509 · Cited by 395 · see citing works
The Cholinergic Hypothesis: A Historical Overview, Current Perspective, and Future Directions
Bartus, R. T., Dean, R. L., Pontecorvo, M. J., & Flicker, C. (1985) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1985.tb37600.x · Cited by 384 · see citing works
Mandrekar-Colucci, S., Karlo, J. C., & Landreth, G. E. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5268-11.2012 · Cited by 355 · see citing works
Yamanaka, M., Ishikawa, T., Griep, A., Axt, D., Kummer, M. P., & Heneka, M. T. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1569-12.2012 · Cited by 326 · see citing works
Geldmacher, D. S., Fritsch, T., McClendon, M. J., & Landreth, G. (2011) · Archives of Neurology · doi:10.1001/archneurol.2010.229 · Cited by 221 · see citing works
Harrington, C. M., Sawchak, S. T., Chiang, C., Davies, J., Donovan, C., Saunders, A. M., Irizarry, M. C., Jeter, B., Zvartau-Hind, M. E., van Dyck, C. H., et al. (2011) · Current Alzheimer Research · doi:10.2174/156720511796391935 · Cited by 198 · see citing works
Bogacka, I., Xie, H., Bray, G. A., & Smith, S. R. (2004) · Diabetes Care · doi:10.2337/diacare.27.7.1660 · Cited by 197 · see citing works
Survival following dementia onset: Alzheimer's disease and vascular dementia
Fitzpatrick, A. L., Kuller, L. H., López, O. L., Kawas, C. H., & Jagust, W. (2004) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2004.11.022 · Cited by 177 · see citing works
Jaakkola, T., Laitila, J., Neuvonen, P. J., & Backman, J. T. (2006) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2006.pto_437.x · Cited by 142 · see citing works
Ko, G.-J., Kang, Y. S., Han, S. Y., Lee, M. H., Song, H. K., Han, K. H., Kim, H. K., Han, J., & Cha, D. R. (2008) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfn157 · Cited by 132 · see citing works
Progress in Alzheimer’s disease
Galimberti, D., & Scarpini, E. A. (2011) · Journal of Neurology · doi:10.1007/s00415-011-6145-3 · Cited by 113 · see citing works
Self-citationProgress of Alzheimer‚s disease
Lawrence, W. S. (2009) · Docs.school Publications · Cited by 68 · see citing works
Bekris, L. M., Galloway, N. M., Montine, T. J., Schellenberg, G. D., & Yu, C. (2009) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30993 · Cited by 63 · see citing works
Roses, A. D., Lutz, M. W., Crenshaw, D. G., Grossman, I., Saunders, A. M., & Gottschalk, W. K. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2012.10.009 · Cited by 63 · see citing works
Journal, C. (2006) · Core evidence · doi:10.2147/ce.s7447 · Cited by 53 · see citing works
Moon, J. H., Kim, H. J., Yang, A. H., Kim, H. M., Lee, B., Kang, E. S., Lee, H. C., & Soo, B. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711001611 · Cited by 47 · see citing works
Toba, J., Nikkuni, M., Ishizeki, M., Yoshii, A., Watamura, N., Inoue, T., & Ohshima, T. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.04.012 · Cited by 41 · see citing works
Scarpini, E. A., Bruno, G., Zappalà, G., Adami, M., Richarz, U., Gaudig, M., Jacobs, A., & Schäuble, B. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110134 · Cited by 37 · see citing works
Self-citationAl‐Majed, A. A., Bakheit, A. H. H., Abdel‐Aziz, H. A., et al. (2016) · Profiles of drug substances, excipients, and related methodology · doi:10.1016/bs.podrm.2015.11.002 · Cited by 33 · see citing works
Jiang, D.-Q., Yang, X., Li, M., Wang, Y., & Wang, Y. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1358-0 · Cited by 28 · see citing works
Efficacy of memantine hydrochloride once-daily in Alzheimer’s disease
Kurz, A., & Grimmer, T. (2014) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2014.945907 · Cited by 22 · see citing works
Transdermal rivastigmine in the treatment of Alzheimer’s disease: current and future directions
Amanatkar, H. R., & Grossberg, G. T. (2014) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2014.955852 · Cited by 8 · see citing works
Clinical drug research in chronic central neurodegenerative disorders
Müller, T. H., & Foley, P. B. (2016) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2016.1163220 · Cited by 7 · see citing works
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Clinical trials of new drugs for Alzheimer disease
Huang, L.-K., Chao, S.-P., & Hu, C.-J. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-019-0609-7 · Cited by 702 · see citing works
Dhapola, R., Hota, S. S., Sarma, P., Bhattacharyya, A., Medhi, B., & Reddy, D. H. (2021) · Inflammopharmacology · doi:10.1007/s10787-021-00889-6 · Cited by 383 · see citing works
Drug development for alzheimer’s disease: Microglia induced neuroinflammation as a target
Dong, Y., Li, X., Cheng, J., & Hou, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030558 · Cited by 136 · see citing works
Is Alzheimer’s Disease a Liver Disease of the Brain?
Bassendine, M. F., Taylor-Robinson, S. D., Fertleman, M., Khan, M., & Neely, D. (2020) · Journal of Alzheimer's Disease · doi:10.3233/jad-190848 · Cited by 124 · see citing works
Fang, J., Zhang, P., Wang, Q., Chiang, C.-W., Zhou, Y., Hou, Y., Xu, J., Chen, R., Zhang, B., Lewis, S. J., et al. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00951-z · Cited by 140 · see citing works
An update on the novel and approved drugs for Alzheimer disease
Alhazmi, H. A., & Albratty, M. (2022) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2022.10.004 · Cited by 122 · see citing works
McMillan, J. M., Mele, B. S., Hogan, D. B., & Leung, A. A. (2018) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2018-000563 · Cited by 80 · see citing works
- Authors
- Galimberti, D., & Scarpini, E.
- Affiliations
- University of Milan (IT)
- Corresponding author
- Galimberti, Daniela
- Venue
- Expert Opinion on Investigational Drugs
- Publisher
- Informa UK Limited
- Published
- 2016-12-04
- Volume
- 26
- Issue
- 1
- Pages
- 97-101
- ISSN
- 1354-3784 (ISSN-L)
- 1744-7658
- OpenAlex
- W2550251289
- Cited by
- 106
- References
- 29
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 11 · 2023: 13 · 2022: 14 · 2021: 15 · 2020: 20 · 2019: 11 · 2018: 9 · 2017: 6
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Investigational Drugs (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- pioglitazone, Alzheimer's disease, thiazolidinediones, PPARγ agonists, insulin sensitizers, pharmacokinetics, pharmacodynamics, drug safety, clinical trials, dementia treatment, cognitive function
- MeSH terms
- Pioglitazone, Aged, Alzheimer Disease, Animals, Cognition, Dementia, Humans, Hypoglycemic Agents, Severity of Illness Index, Disease Progression, Thiazolidinediones, PPAR gamma
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