確認第2型糖尿病的適當胰島素處方劑量
作者：Alison Palkhivala
出處：WebMD醫學新聞
October 26, 2009 (蒙特婁) — 根據發表於國際糖尿病聯盟(International Diabetes Federation，IDF)第20屆世界糖尿病研討會的一篇隨機試驗結果，需要使用胰島素的第2型糖尿病患，如果先用基礎胰島素，有需要時再加入餐前胰島素，效果會最好。該研究也線上發表於10月22日的新英格蘭醫學期刊(New England Journal of Medicine)。
【胰島素治療無共識】
發表人、第一作者、英國牛津大學糖尿病試驗小組主任、糖尿病醫學教授Rury Holman醫師向Medscape Diabetes and Endocrinology表示，第2型糖尿病是一種漸漸惡化的狀況，多數病患後來都需要胰島素治療。全球對於第2型糖尿病的胰島素治療方法各有不同考量，但是未曾對複雜的胰島素處方進行大規模的直接比較。有關應該先使用哪種胰島素處方或哪種複方胰島素處方最適當，並沒有具實證基礎的共識。
在這三年的開放標籤多中心研究中，Holman醫師等人將糖化血色素值(HbA1c)欠佳的708名第2型糖尿病患者，不管服用metformin和磺醯尿素類，隨機分派接受三種胰島素處方之一。第一種處方包括雙效胰島素(商品名NovoMix 30)、每天兩次，第二種處方包括餐前胰島素(商品名NovoRapid) 、每天三次，第三種處方包括基礎胰島素determir(商品名Levemir)、每天一次(需要時才給予第二次)。如果在治療第一年發生無法接受的高血糖或HbA1c值依舊超過6.5%，可以用第二種胰島素取代磺醯尿素類治療。使用雙效胰島素的病患加入每天一次的餐前胰島素，使用餐前胰島素的病患加入每天一次的基礎胰島素，使用基礎胰島素的病患加入每天三次的餐前胰島素。
主要結果是測量HbA1c值、HbA1c值小於等於6.5%的病患比率、低血糖事件比率以及體重增加情況。
【基礎胰島素、需要時加入餐前胰島素這組的結果最好】
追蹤三年結束時，三組病患的HbA1c中位數值相似：雙效胰島素組為7.1%、餐前胰島素組為6.8%、餐前胰島素組為6.9%。雙效胰島素組達到HbA1c值小於6.5%的病患比率(31.9%)比餐前胰島素組(44.7%)和基礎胰島素組(43.2%)少。同樣的，雙效胰島素組只有67.7%的病患需要第二種的胰島素，餐前胰島素組有81.6%、基礎胰島素組有73.6%需要。
基礎胰島素組的低血糖事件比率中位數為1.7%，但是其他兩組較高：雙效胰島素組為3.0%，餐前胰島素組為5.7% 。餐前胰島素組的平均體重增加較多(6.4公斤)，雙效胰島素組為5.7公斤、基礎胰島素組3.6公斤。三組的其他副作用比率相似。
Holman醫師表示，四分之三的病患需要加入第二種胰島素。相較於雙效胰島素組，以基礎胰島素或餐前胰島素開始治療者，有較佳的HbA1c控制。以基礎胰島素開始治療者發生的低血糖事件較少、體重增加較少，腰圍則略為增加。這些發現首度提供支持以每天一次的基礎胰島素開始治療第2型糖尿病患、如果未達血糖目標才於用餐時加入餐前胰島素的清楚實證。
杜賽道夫UKD Heinrich Heine大學代謝科、德國糖尿病中心主任Michael Roden醫師為新英格蘭醫學期刊寫編輯評論。他向Medscape Diabetes and Endocrinology表示，對我們來說，該報告確認了第2型糖尿病使用胰島素治療的現有指引與共識。這些建議之前因為缺乏證據而沒有太多醫師接受。我們最後獲得第2型糖尿病使用胰島素治療的證據，認為開始時先使用基礎胰島素，之後漸漸增加劑量。不過，特別要注意的是，作者們使用的胰島素都是來自Novo-Nordisk這家藥廠，因此這些資料套用到其他胰島素製劑時是否依舊成立也值得討論。
該研究接受Novo Nordisk藥廠的資助。Holman醫師宣告接受Novo Nordisk藥廠的資助且擔任其諮詢委員。Roden醫師接受Novo Nordisk藥廠的演講費用。
國際糖尿病聯盟(IDF)第20屆世界糖尿病研討會。摘要0562，發表於2009年10月22日。
N Engl J Med. 線上發表於2009年10月22日。
Optimal Insulin Dosing Regimen for Type 2 Diabetes Identified
By Alison Palkhivala
Medscape Medical News
October 26, 2009 (Montreal, Quebec) — Type?2 diabetic patients requiring insulin will do best if they start with a basal insulin and then add prandial insulin as needed, according to the results of a randomized trial presented here at the International Diabetes Federation 20th World Diabetes Congress. The research was published online October 22 in the New England Journal of Medicine.
No Consensus on Insulin Therapy
"Type?2 diabetes is a progressive condition, with the majority of patients requiring insulin therapy in the longer term," presenter and lead author Rury Holman, MB, professor of diabetic medicine and director of the University of Oxford Diabetes Trials Unit in the United Kingdom, told Medscape Diabetes and Endocrinology. "Approaches to insulin therapy for type?2 diabetes vary considerably across the world, but large-scale direct comparisons of complex insulin regimens have not been performed. There is no evidence-based consensus about which insulin formulation should be used to initiate insulin therapy or which complex insulin regimen might be most appropriate."
In a 3-year open-label multicenter study, Dr. Holman and colleagues randomized 708 type?2 diabetes patients who had suboptimal glycated hemoglobin (HbA1c) levels, despite taking metformin and sulfonylurea, to 1 of 3 insulin regimens. The first regimen consisted of biphasic insulin aspart (NovoMix?30) dosed twice daily, the second consisted of prandial insulin aspart (NovoRapid) dosed 3 times daily, and the third consisted of basal insulin determir (Levemir) dosed once daily (and a second time if required). If hyperglycemia became unacceptable during the first year of therapy or if HbA1c levels subsequently remained over 6.5%, the sulfonylurea therapy could be replaced with a second type of insulin. Patients taking biphasic insulin added prandial insulin once daily, patients taking prandial insulin added basal insulin once daily, and patients taking basal insulin added prandial insulin 3 times day.
The primary outcome measures were HbA1c level, proportion of patients with an HbA1c of 6.5% or less, rate of hypoglycemia, and weight gain.
Best Outcomes With Basal Insulin, With Addition of Prandial Insulin if Needed
At the end of 3 years of follow-up, median HbA1c levels were similar for all 3 groups of patients: 7.1% in the biphasic group, 6.8% in the prandial group, and 6.9% in the prandial group. A smaller proportion of patients achieved an HbA1c level under 6.5% in the biphasic group (31.9%) than either the prandial group (44.7%) or the basal (43.2%) group. Similarly, only 67.7% of patients in the biphasic group required a second type of insulin, compared with 81.6% in the prandial group and 73.6% in the basal group.
The median rate of hypoglycemia was 1.7% in the basal group, but it was higher in the other 2 groups: 3.0% in the biphasic group and 5.7% in the prandial group. Mean weight gain was higher in the prandial group (6.4?kg) than in either the biphasic (5.7?kg) or basal (3.6?kg) group. Other adverse events were similar for all 3 groups.
"Three-quarters of patients needed to add a second insulin," said Dr. Holman. "Those commencing therapy with a basal or prandial based insulin had better HbA1c control than patients commencing with a biphasic insulin. Patients commencing therapy with basal insulin had fewer hypoglycemic episodes, less weight gain, and a smaller increase in their waist circumference.?.?.?. These findings provide clear evidence to support starting insulin therapy in people with type?2 diabetes with a once a day basal insulin with the subsequent addition of a mealtime insulin if glycemic targets are not met."
Michael Roden, MD, director of the German Diabetes Center and the Department of Metabolic Diseases at UKD Heinrich Heine University in Dusseldorf, wrote an editorial to accompany the article in the New England Journal of Medicine. He told Medscape Diabetes and Endocrinology that, "for many of us, the paper confirms current guidelines/consensus reports on insulin treatment in type?2 diabetes. [These recommendations were] not [followed] by many doctors due to lack of evidence.?.?.?. [We finally have evidence that] insulin therapy in type?2 [diabetic patients] should by started with basal insulin and then progressively increased [in] dosage.?.?.?.? Of note, [however], the authors used only insulin analogs from 1 company [Novo-Nordisk], which leaves open whether these data hold true for human insulin analogs."
This study received funding from Novo Nordisk. Dr. Holman has received funding from and sits on an advisory board for Novo Nordisk. Dr. Roden has received lecture fees from Novo Nordisk.
International Diabetes Federation (IDF) 20th World Diabetes Congress. Abstract 0562 Presented October 22, 2009.
N Engl J Med. Published online October 22, 2009.
