羅曼死

作者：Laurie Barclay, MD  
出處：WebMD醫學新聞

　　June 2, 2010 — 口服抗糖尿病藥物（OADs）大約可以降低糖化血色素（A1C）濃度達0.5%-1.25%。根據一項系統性綜論與綜合分析結果，最大效果大約發生在3-6個月，且thiazolidinediones與sulfonylureas的效果最好。
　　
　　加拿大安大略漢米爾頓曼徹斯特大學內科部Diana Sherifali博士與其同事們在糖尿病照護（Diabetes Care）期刊上報告，且於5月18日線上發表。
　　
　　研究者們寫到，過去研究的總結是，OADs約可降低A1C濃度0.5%-1.5%。然而，A1C濃度下降的估計值是根據不同研究設計的結論，這可能導致OADs真實效應被高估或低估。
　　
　　目前這項研究使用預先確立的標準來更精確地決定OADs對A1C濃度的影響。
　　
　　Sherifali博士與其同事們搜尋醫學文獻，找尋於1980年到2008年5月之間發表的隨機分派安慰劑控制研究。總共有61項研究由兩位獨立研究者篩選出來。這些研究共收納26,367位受試者，將近15,000位被隨機分派接受治療，其他受試者被隨機分派至安慰劑組。
　　
　　OAD藥物包括alpha糖解酶抑制劑、biguanides、雙胜胜肽酶-4抑制劑、meglitinides、sulfonylureas與thiazolidinediones。整體來看，OADs降低A1C濃度達0.5%-1.25%，thiazolidinediones與sulfonylureas降低A1C濃度程度較大，大約是1.0%-1.25%。
　　
　　除此之外，服藥前較高的A1C濃度也與6個月OAC治療後下降較多有關；相反的，罹病時間長短對於OADs反應並無影響。
　　
　　作者們的結論是，開始使用一種OAD藥物的好處大約在前4至6個月就可以看到，A1C濃度不太可能下降超過平均1.5%。
　　
　　根據研究者們表示，需要之後嚴謹執行的OAD研究，來解釋合併OAD藥物使用以及對A1C濃度的影響，長期使用OAD的效果、以及潛在不良事件。
　　
　　【試驗限制】
　　獨立評論者Philip Home哲學博士，他是Newcastle大學的糖尿病醫學教授，他向Medscape糖尿病與內分泌學表示，這項研究限制在於療效時程不明的研究被排除在外，這已知在sulfonylureas與其他口服降血糖藥物比較時是不同的，使得這樣的研究要比較療效是有困難的。
　　
　　Home博士向Medscape糖尿病與內分泌學表示，專家們應該對所有口服藥物有限的療效提高警覺，早期且頻繁地監測，不要等到病患已經血糖控制持續高於目標值造成的後果所苦。
　　
　　這項研究由Merck Frosst公司贊助。Sherifali博士接受安大略心臟與中風基金會的資助。共同作者Kara Nerenberg醫師接受加拿大健康研究機構的資助。共同作者Hertzel C. Gerstein醫師接受藥廠提供的諮詢或是演講費用。這些公司包括sanofi-aventis、Bristol-Myers Squibb、AstraZeneca、Bayer、GlaxoSmithKline、Lilly、Novo Nordisk、Biovail、Servier與Roche。Home博士是Medscape糖尿病與內分泌學的編輯團，且表示與AstraZeneca Pharmaceuticals LP、Bristol-Myers Squibb Co、Boehringer-Ingelheim Pharmaceuticals有限公司、GlaxoSmithKline、MannKind Corp、Merck Co有限公司、Novo Nordisk、Novartis Pharmaceuticals Corp、Roche、sanofi-aventis、Tolerx有限公司、XOMA（美國）LLC與Lilly有不同的資金往來。


Thiazolidinediones and Sulfonylureas Most Effective in Lowering HbA1C

By Laurie Barclay, MD
Medscape Medical News

June 2, 2010 — Oral antidiabetic drugs (OADs) decrease glycosylated hemoglobin (A1C) levels by approximately 0.5% to 1.25%. The maximal effect is achieved by 3 to 6 months, and thiazolidinediones and sulfonylureas show the greatest efficacy, according to the findings of a systematic review and meta-analysis.

Diana Sherifali, PhD, from the Department of Medicine, McMaster University, Hamilton, Ontario, Canada, and colleagues reported their findings in Diabetes Care, published online ahead of print on May 18.

"Summaries of previous studies of ...OADs suggest that they reduce A1C levels by 0.5-1.5%," the researchers write. "However, this estimated drop in A1C was based on summaries of studies with varying designs, which may lead to over or under estimates of the true effect of OADs."

The current study used predetermined methodologic criteria to determine the effect of OADs on A1C levels more accurately.

Dr. Sherifali and colleagues searched several databases on the medical literature for randomized, placebo-controlled studies published between 1980 and May 2008. A total of 61 trials were selected by 2 independent evaluators. The studies included 26,367 study participants, with approximately 15,000 randomly assigned to treatment and the remainder randomly assigned to placebo.

OAD drug classes included were the alpha glucosidase inhibitors, biguanides, dipeptidyl peptidase-4 inhibitors, meglitinides, sulfonylureas, and thiazolidinediones. Overall, OADs lowered A1C levels by 0.5% 1.25%, whereas thiazolidinediones and sulfonylureas lowered A1C levels, to a slightly greater extent, by approximately 1.0% to 1.25%.

In addition, a higher baseline A1C level was associated with a greater decline in A1C levels with 6 months of OAD treatment; by contrast, the length of disease duration had no effect on response to OADs.

The authors concluded that the benefit of initiating an OAD agent is most apparent within the first 4 to 6 months, with A1C levels unlikely to decrease more than 1.5% on average.

According to the researchers, further carefully conducted OAD trials are needed to account for combinations of OAD drug use and its impact on A1C levels, the effectiveness of long-term OAD use, and the potential for adverse events.

Study Limitations

Independent commentator Philip Home, DM, DPhil, MA, professor of diabetes medicine at Newcastle University, told Medscape Diabetes Endocrinology that limitations of the study were that comparative trials were excluded and that the time course of efficacy is known to be different for sulfonylureas vs other oral medications, which makes comparing efficacy difficult in a study such as this.

"Professionals need to be aware of the limited efficacy of all oral agents, to monitor response early and at frequent intervals, and to add further agents without waiting for their patients to suffer the consequences of continued glucose control above target levels," Dr. Home told Medscape Diabetes Endocrinology.

The study was sponsored by an unrestricted grant from Merck Frosst. Dr. Sherifali has received support through the Heart and Stroke Foundation of Ontario. Coauthor Kara Nerenberg, MD, MSc, has received support through the Canadian Institutes of Health Research. Coauthor Hertzel C. Gerstein, MD, MSc, has received honoraria for providing advice or speaking. These companies include sanofi-aventis, Bristol-Myers Squibb, AstraZeneca, Bayer, GlaxoSmithKline, Lilly, Novo Nordisk, Biovail, Servier, and Roche.

Dr. Home is on the Medscape Diabetes Endocrinology editorial board and has disclosed various financial relationships with AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb Co; Boehringer-Ingelheim Pharmaceuticals, Inc; GlaxoSmithKline; MannKind Corp; Merck & Co, Inc; Novo Nordisk; Novartis Pharmaceuticals Corp; Roche; sanofi-aventis; Tolerx, Inc; XOMA (US) LLC; and Lilly.

Diabetes Care. Published online May 18, 2010.