Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA.
Ann Pharmacother. 2011 Nov;45(11):1416-24. doi: 10.1345/aph.1Q238. Epub 2011 Oct 25.
To review the literature on the efficacy and safety of rosiglitazone and pioglitazone for the treatment of Alzheimer's disease (AD).
Literature was accessed through MEDLINE (1948-August 2011 week 2) and EMBASE (1980-2011 week 32) using the search terms rosiglita-zone, pioglitazone, and Alzheimer's disease. Results were limited to studies conducted in humans and published in English.
Clinical trials evaluating the efficacy and safety of rosiglitazone or pioglitazone in patients with AD were critically evaluated.
The mechanism for development of AD has been linked to both inflammation and decreased insulin sensitivity. Because of this, rosiglitazone and pioglitazone have been evaluated as potential treatments for AD because of their insulin-sensitizing and antiinflammatory effects. Five clinical trials were evaluated (3 assessing rosiglitazone, 2 assessing pioglitazone); 1 trial evaluating rosiglitazone demonstrated a beneficial effect on cognition in patients with probable AD. However, the largest randomized, double-blind, placebo-controlled trials conducted to date failed to demonstrate a difference between rosiglitazone and placebo when assessing primary endpoints. Two small trials evaluating pioglitazone produced conflicting results regarding efficacy in AD; numerous limitations make results difficult to interpret. The safety of these agents was also evaluated in these trials; edema was seen more commonly in patients receiving rosiglitazone or pioglitazone than in those receiving placebo; however, each drug was generally well tolerated.
Results from clinical trials and current safety data suggest that rosiglitazone should not be used for the treatment of AD. Application of results from trials evaluating pioglitazone in the treatment of AD is limited because of major trial limitations; therefore, it should not be recommended at this time. Although these drugs are not commonly used in the treatment of AD, further pharmacoepidemiologic studies are warranted before their use can be recommended.
综述罗格列酮和吡格列酮治疗阿尔茨海默病（AD）的疗效和安全性的文献。
通过 MEDLINE（1948 年-2011 年 8 月第 2 周）和 EMBASE（1980 年-2011 年第 32 周）检索文献，检索词为罗格列酮、吡格列酮和阿尔茨海默病。结果仅限于在人类中进行的并以英文发表的研究。
对评估 AD 患者罗格列酮或吡格列酮疗效和安全性的临床试验进行了严格评价。
AD 的发病机制与炎症和胰岛素敏感性降低均有关。正因为如此，罗格列酮和吡格列酮因其具有胰岛素增敏和抗炎作用而被评估为 AD 的潜在治疗药物。评价了 5 项临床试验（3 项评估罗格列酮，2 项评估吡格列酮）；1 项评估罗格列酮的试验显示该药物对可能患有 AD 的患者的认知功能有有益影响。然而，迄今为止进行的最大规模的随机、双盲、安慰剂对照试验未能显示罗格列酮与安慰剂在评估主要终点时的差异。评估吡格列酮在 AD 中的疗效的两项小型试验结果相互矛盾；大量局限性使结果难以解释。这些试验还评估了这些药物的安全性；与接受安慰剂的患者相比，接受罗格列酮或吡格列酮治疗的患者更常见水肿；然而，每种药物通常都具有良好的耐受性。
临床试验的结果和当前的安全性数据表明，罗格列酮不应用于治疗 AD。由于主要试验局限性，评估吡格列酮治疗 AD 的试验结果的应用受到限制；因此，目前不应推荐使用。尽管这些药物在 AD 的治疗中不常用，但在推荐使用之前，还需要进行进一步的药物流行病学研究。
