Trial reportCurrent Alzheimer research2011
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.
Trial report in Current Alzheimer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 98 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Insulin Resistance and Mild Cognitive Impairment (MCI) in Older Chinese Adults With Pre-Diabetes and Diabetes: Cognitive Effects of Lifestyle Intervention and Metformin Treatment in a Randomized Controlled Trial
A 54 Week, Double-blind, Randomised, Placebo-controlled, Parallel Group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy to Acetylcholinesterase Inhibitors on Cognition and Overall Clinical Response in APOE4-stratified Subjects With Mild to Moderate Alzheimer's Disease
A 54-week, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy to Donepezil on Cognition and Overall Clinical Response in APOE ε4-stratified Subjects With Mild to Moderate Alzheimer's Disease.
An Open-label Extension to Study AVA102670 and AVA102672, to Assess the Long-term Safety and Efficacy of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy on Cognition in Subjects With Mild to Moderate Alzheimer's Disease.
Who cites it
98 citing papers in PubMed, 4 syntheses or guidelines pooled it, 192 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Efficacy and safety of hypoglycemic drugs in improving cognitive function in patients with Alzheimer's disease and mild cognitive impairment: A systematic review and network meta-analysis.Frontiers in neurology · 2022Pooled it
- Proportion of Women and Reporting of Outcomes by Sex in Clinical Trials for Alzheimer Disease: A Systematic Review and Meta-analysis.JAMA network open · 2021Pooled it
- Peroxisome proliferator-activated receptor-gamma agonists for Alzheimer's disease and amnestic mild cognitive impairment: a systematic review and meta-analysis.Drugs & aging · 2015Pooled it
- A Precision Medicine Approach to Treating Alzheimer's Disease Using Rosiglitazone Therapy: A Biomarker Analysis of the REFLECT Trials.Journal of Alzheimer's disease : JAD · 2021Trial
- Donepezil Plus Solifenacin (CPC-201) Treatment for Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Trial
- An evaluation of MSDC-0160, a prototype mTOT modulating insulin sensitizer, in patients with mild Alzheimer's disease.Current Alzheimer research · 2014Trial
- Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study.Alzheimer disease and associated disordersTrial
- The Substrate-Engine Model of Ferroptosis: Stage-Specific Targeting of Acyl-CoA Synthetase Long-Chain Family Member 4 and 5‑Lipoxygenase in Alzheimer's Disease.ACS pharmacology & translational science · 2026Review
- Amelioration of behavioral and neural deficits in animal models of neurodegenerative disease by nanoformulations of curcumin and quercetin.Neural regeneration research · 2026Article
- Article
- Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer's Disease? A Review of Recent Pertinent Observations from Molecular Biology.International journal of molecular sciences · 2025Review
- Exploring the Mechanisms and Therapeutic Approaches of Mitochondrial Dysfunction in Alzheimer's Disease: An Educational Literature Review.Molecular neurobiology · 2025Review
- Lipidome disruption in Alzheimer's disease brain: detection, pathological mechanisms, and therapeutic implications.Molecular neurodegeneration · 2025Review
- Patient stratification by genetic risk in Alzheimer's disease is only effective in the presence of phenotypic heterogeneity.PloS one · 2025Article
- Alzheimer's disease phenotype based upon the carrier status of the apolipoprotein E ɛ4 allele.Brain pathology (Zurich, Switzerland) · 2024Review
- New insights in lipid metabolism: potential therapeutic targets for the treatment of Alzheimer's disease.Frontiers in neuroscience · 2024Review
- siRNA drug delivery across the blood-brain barrier in Alzheimer's disease.Advanced drug delivery reviews · 2023Review
- The Deficits of Insulin Signal in Alzheimer's Disease and the Mechanisms of Vanadium Compounds in Curing AD.Current issues in molecular biology · 2023Review
- Repositioning of Anti-Diabetic Drugs against Dementia: Insight from Molecular Perspectives to Clinical Trials.International journal of molecular sciences · 2023Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTwo 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.
methodsIn 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.
resultsNo statistically or clinically relevant differences between treatment groups were observed on the a priori primary endpoints in REFLECT-2 or REFLECT-3. Edema was the most frequent adverse event with RSG in each study (14% and 19%, respectively, at 8 mg RSG XR).
conclusionsNo evidence of statistically or clinically significant efficacy in cognition or global function was detected for 2 mg or 8 mg RSG XR as adjunctive therapy to ongoing AChEIs. There was no evidence of an interaction between treatment and APOE status. Safety and tolerability of RSG XR was consistent with the known profile of rosiglitazone.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.