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Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies
Harrington C, Sawchak S, Chiang C, Davies J, Donovan C, Saunders AM, Irizarry M, Jeter B et al.. Current Alzheimer research, 2011-08-01
Topic: Amyloid, tau and blood-test diagnosis
Introduction Two phase 3 studies evaluated the efficacy and safety of rosiglitazone (RSG), a type 2 diabetes treatment, in an extended release (RSG XR) form as adjunctive therapy to ongoing acetylcholine esterase inhibitor (AChEI) treatment in AD (REFLECT-2, adjunctive to donepezil; REFLECT-3, to any AChEI). An open-label extension study (REFLECT-4) assessed RSG XR long-term safety. Methods In these two double-blind, placebo-controlled studies, subjects with mild-to-moderate probable AD were randomized within 2 apolipoprotein E (APOE) allelic strata (APOE ε4-positive, APOE ε4-negative) to once daily placebo, 2 mg RSG XR, or 8 mg RSG XR for 48 weeks (REFLECT-2, N=1,496; REFLECT-3, N=1,485).
Key findings
- An open-label extension study (REFLECT-4) assessed RSG XR long-term safety.
- Methods In these two double-blind, placebo-controlled studies, subjects with mild-to-moderate probable AD were randomized within 2 apolipoprotein E (APOE) allelic strata (APOE ε4-positive, APOE ε4-negative) to once daily placebo, 2 mg RSG XR, or 8 mg RSG XR for 48 weeks (REFLECT-2, N=1,496; REFLECT-3, N=1,485).
- Co-primary efficacy endpoints were change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Clinical Dementia Rating scale - Sum of Boxes (CDR-SB) scores at week 48.
- Three populations were analyzed: APOE4-negative, all subjects except APOE ε4 homozygotes, and the full intent-to-treat population.
Why it matters
Two phase 3 trials found that rosiglitazone, added to ongoing cholinesterase inhibitor treatment, did not improve cognition or global function in mild-to-moderate Alzheimer's disease. This is a clear negative result: the drug did not help patients in these studies.
Study details
- Study designclinical trial
- Participants1,496
- Evidence strengthHigh
How this study scored 64/100
Published in a peer-reviewed journal, and it is a large phase 3 trial. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Current Alzheimer research) |
| Journal's citation record | 1 / 4 | Current Alzheimer Research: journal h-index 119 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A large phase 3 trial (from PubMed type “Clinical Trial, Phase III”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,496 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 196 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.5 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 3 / 6 | Cited 6.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 2 / 4 | Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Maike Gold: h-index 15 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | GlaxoSmithKline (United States): institution h-index 621 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21592048) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Harrington, C., Sawchak, S., Chiang, C., Davies, J., Donovan, C., Saunders, A. M., et al. (2011). Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies. Current Alzheimer research. https://doi.org/10.2174/156720511796391935
Vancouver
Harrington C, Sawchak S, Chiang C, Davies J, Donovan C, Saunders AM, et al. Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies. Current Alzheimer research. 2011. doi:10.2174/156720511796391935. PMID: 21592048.
BibTeX
@article{harrington2011-21592048,
author = {Harrington, C. and Sawchak, S. and Chiang, C. and Davies, J. and Donovan, C. and Saunders, A. M. and Irizarry, M. and Jeter, B. and others},
title = {{Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies}},
journal = {Current Alzheimer research},
year = {2011},
doi = {10.2174/156720511796391935},
pmid = {21592048},
url = {https://doi.org/10.2174/156720511796391935}
}
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