VIENNA (EGMN) – Glycemic control was maintained over 5 years using metformin, sulfonylureas, and insulin almost exclusively in a longitudinal study of cholesterol lowering in 4,900 patients with type 2 diabetes.
The findings call into question the need for new diabetes drugs, especially now that increased emphasis is being placed on the safety of these agents, Dr. James Best said at the annual meeting of the European Association for the Study of Diabetes.
The finding comes from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, which investigated whether fenofibrate could reduce the risk of cardiovascular disease in patients with type 2 diabetes in Finland, Australia, and New Zealand (Lancet 2005;366:1849-61). FIELD failed in its primary end point, but because its design did not involve modifying any aspect of glycemic management, it offered a real-world opportunity to see what happened over time with standard care for diabetes, mainly in primary care settings,
The results suggest that diabetes control can be effectively maintained using the three oldest and least expensive classes of diabetes drugs, and challenges the prevailing belief that new types of glucose-lowering drugs are needed. “There’s this background subtext that diabetes control inexorably deteriorates despite optimal therapy and therefore we need to find new drugs to treat this disease. My message is that we don’t,” Dr. Best, professor of medicine and head of the school of medicine at the University of Melbourne, said in an interview. At baseline, the study population had a mean age of 62 years and diabetes duration of 5 years. Just over a third were women. They were reasonably well controlled at baseline, with a median hemoglobin A1c of 6.9%, even though 26% were on no diabetes medications, 60% were on oral agents only, and just 14% were using insulin. Median body weight was 86.3 kg.
Over the subsequent 5 years, the median HbA1c rose slightly (0.22 percentage points), to just over 7.0%, while body weight fell slightly, to 85.0 kg. Oral hypoglycemic medication – nearly all metformin, sulfonylureas, or both – was initiated in 56% of the 1,287 who had been taking no medications at baseline, and insulin was started in 25% of the 2,917 who had not been taking it at baseline. Thus, at 5 years, 77% of patients were on oral agents and 28% were on insulin, but only 4% were on oral agents other than sulfonylureas or metformin, Dr. Best reported.
The 0.22 percentage-point increase in HbA1c seen in FIELD is in contrast to the 1.0 percentage-point rise that occurred in the landmark U.K. Prospective Diabetes Study (UKPDS), which is often cited as evidence for the inevitable decline in glucose control in patients with type 2 diabetes (Lancet 1998;352:837-53).
The findings support the new emphasis on cardiovascular safety that regulatory bodies are now imposing on all glucose-lowering drugs, following reports of adverse cardiovascular outcomes with the thiazolidinedione (TZD) rosiglitazone, Dr. Best said.
“I see much less urgency for new therapies. We need safety outcomes for new treatments, rather than just efficacy. The TZDs are a good example. They got to market before there was really safety data, on the grounds that glycemic control deteriorates with standard treatment and therefore we needed them. Now that we’ve seen the safety outcomes, their use should be much more limited than was thought initially.”
Dr. Best stated that he had no financial disclosures.
Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
维也纳(EGMN)——一项纳入4,900例2型糖尿病患者的降胆固醇纵向研究显示,单纯应用二甲双胍、磺脲类药物、胰岛素便能维持血糖控制长达5年。
James Best博士在欧洲糖尿病研究协会年会上说,该结果对新型糖尿病药物的需要提出了质疑,特别是目前这些药物的安全性正在被日益重视。
该结果来自非诺贝特干预降低糖尿病事件研究(FIELD)。这一研究在芬兰、澳大利亚和新西兰的2型糖尿病患者中探讨了非诺贝特是否能够降低心血管疾病风险(Lancet 2005;366:1849-61)。FIELD研究未达到主要终点,但由于其设计并未涉及修改血糖控制方案的任何方面,因此能够(主要在初级保健治疗环境中)真正观察到随时间推移出现的标准糖尿病治疗相关情况。
研究结果表明,应用这3种最传统且最便宜的糖尿病药物能够有效地维持血糖控制。这对有关需要新型降糖药物的现行观点提出了质疑。墨尔本大学医学院负责人兼内科学教授的Best博士在接受采访时说: “有些人认为,治疗对糖尿病的控制效果不可避免地会降低,即使给予最佳治疗也不例外,因此我们需要探索治疗该病的新型药物。我认为,我们并不需要新型药物。”在基线时,研究人群的平均年龄是62岁,糖尿病病程是5年。女性所占的比例略超过1/3。基线时,尽管26%的患者未服用任何糖尿病药物,60%仅服用口服药物,仅14%使用胰岛素,但是这些患者的血糖控制效果相当好,中位血红蛋白A1c水平为6.9%,中位体重为86.3 kg。
Best 博士报告,在随后5年中,中位HbA1c水平轻微升高,略超过7.0%,而体重轻微下降至85.0 kg。在基线时未服用任何药物的1,287例患者中,有56%开始服用口服降血糖药(几乎均为二甲双胍、磺脲类药物或两者联用)。在基线时未使用胰岛素的2,917例患者中,有25%开始使用胰岛素。因此,在5年中,77%的患者服用口服药物,28%使用胰岛素,但仅4%服用除了磺脲类药物或二甲双胍之外的其他口服药物。
在FIELD 研究中观察到HbA1c 水平增加0.22%,相比之下,里程碑式英国前瞻性糖尿病研究(UKPDS)中的HbA1c 水平增加了1.0%。后者常作为证据被用于证明2型糖尿病患者的血糖控制效果势必降低 (Lancet 1998;352:837-53)。
Best博士表示,在噻唑烷二酮类药物(TZD)罗格列酮相关不良心血管转归见诸报道之后,该研究结果支持目前监管部门强调提高所有降血糖药物的心血管安全性的新要求。
他说:“我看不出对新型治疗药物的需求有多紧迫。我们希望新型治疗药物能够带来安全的预后,而不仅仅是疗效。TZD就是个好例子。TZDs在安全性数据真正出来之前就得以上市,由于标准治疗对血糖的控制效果会降低,因此我们需要TZDs。 既然我们已经了解了他们的安全性结果,因此应比起初更为有限地应用他们。”
Best博士声明其无任何需披露的利益关系。
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