新确诊的2型糖尿病患者采用药物联合治疗策略优于分步治疗策略

一项随机试验显示，新诊断2型糖尿病患者一开始就给予三药联合治疗，其疗效要好于从二甲双胍开始的分步治疗，它能使血糖保持更低的水平，更长的时间。

来自德克萨斯大学健康中心的Muhammad Abdul-Ghani博士和他的同事发现，同时联合二甲双胍、匹格列酮和艾塞那肽三药治疗，24个月时糖化血红蛋白A1c为6%，而传统治疗单药二甲双胍，再加用磺脲类降糖药，再结合胰岛素分步治疗的糖化血红蛋白A1c为6.6% (P<0.001)。研究小组在美国糖尿病协会的会议上报道，药物使用达最大剂量后仍不能保证糖化血红蛋白A1c低于6.5%则认为治疗失败，起始即为联合治疗组的治疗失败时间明显长于分步治疗组，24个月时联合治疗组只有17%病人治疗失败，而在分步治疗组则42%。同时在联合治疗组病人体重减轻并较少发生低血糖，相反分步治疗组病人体重增加。

Abdul-Ghani 告诉MedPage Today：“如果这种差距能维持更长的时间，那么想想将会减少多少微血管病变以及由此而节约的治疗费用。”他暗示这个结果可能会抵消因为多种药物提前联合使用带来的费用增加。来自纽约芒特西奈的Ronald Tamler医生这样评论，这种积极的治疗方法对于年轻的病人可能是更好的选择，因为他们总是想要做一切他们能做的事情来治疗糖尿病。Tamler同时也指出，现今临床实践中所应用的联合治疗方案真的不是很有吸引力，尤其在匹格列酮被警告有增加膀胱癌风险之后，同时还因为目前临床应用的方案较试验中的方案更为保守，其糖化血红蛋白A1c低于7%即达标。在MedPage Today访谈中他继续补充说，其它在实践中还需关注的问题是每天注射药物、联合使用多种药物的依从性。达拉斯糖尿病和内分泌中心的仲裁委员Julio Rosenstock医生说，这个结论同样是有争议的。

试验包括155名未经药物治疗的新诊断的2型糖尿病患者，随机分入开放性治疗实验组。联合治疗组药物剂量经过爬坡最后达到二甲双胍2,000 mg，匹格列酮30 mg，艾塞那肽10 mcg，1日1次使用药物，在试验的第一个月糖化血红蛋白要低于6.5%。对照组病人初始给予二甲双胍1,000 mg/天，如疗效不满意逐渐加量至2,000 mg/天，如果在1个月时空腹血糖仍超过100 mg/dL，则加用优降糖5mg/天。在第2个月时如果血糖仍超过100 mg/dL或是糖化血红蛋白没有达到治疗目标低于6.5%，则优降糖的剂量加倍。第3个月时如果治疗目标仍未达到，仍加用甘精胰岛素10U/天，如果血糖持续超过100 mg/dL则胰岛素每周增加10U。在最初的3个月后病人每三个月随访一次，药物剂量根据是否有低血糖或是其相应的症状进行下调。联合治疗组平均糖化血红蛋白A1c降至5.8%，而传统治疗组为6.4%。联合治疗组几乎所有病人糖化血红蛋白A1c水平都达到了美国糖尿病协会推荐的要求——低于7.0%（92%），传统治疗组则只有72% (P<0.001)。在最大药物治疗量下，联合治疗组84%病人的糖化血红蛋白A1c水平低于6.5%。联合治疗组糖化血红蛋白A1c水平低于6.0%的病人是分步治疗组的2倍(60% versus 27%, P<0.001)。治疗达24个月时，联合治疗组病人体重下降2.6磅，传统治疗组则增加9.0磅(-1.2 versus +4.1 kg, P<0.001)。3药联合治疗组低血糖发生率为15%，而分步治疗组为46%。Tamler说这并不奇怪，因为选择的药物不同。需要第三方介入的严重低血糖事件在二组都没有发生。联合治疗组消化道副反应更常见(33% versus 21%)，二组间总的副反应发生率相似。

正如Tamler所说的那样，这个研究的局限性在于，这是一个“苹果与桔子的比较”，因为二种治疗方法所包括的药物是不同的，同时这个研究的入组病人量也较小。

（丁香园：月下荷花）

ADA: Drug Combo Beats Step-Up Tx in New T2D

Starting newly-diagnosed type 2 diabetes patients on triple combination therapy rather than progressing step-wise up from metformin keeps glucose lower for longer, a randomized trial showed.

Hemoglobin A1c at 24 months was 6% with the combination of metformin, pioglitazone (Actos), and exenatide (Byetta) compared with 6.6% on the conventional strategy of metformin alone then addition of a sulfonylurea and then basal insulin (P<0.001), Muhammad Abdul-Ghani, MD, PhD, of the University of Texas Health Science Center in San Antonio, and colleagues found.

Time to failure in keeping A1c under the target 6.5% on maximal therapy was significantly longer with the initial combination, with 17% of patients in that category by 24 months versus 42% with the step-wise strategy, the group reported here at the American Diabetes Association meeting.

It also was associated with less hypoglycemia and weight loss, instead of weight gain as seen with the sequential strategy.

"If that difference really can be maintained for a longer period of time, think how much that translates into microvascular complications and how much cost that is going to save," Abdul-Ghani told MedPage Today, suggesting it might offset the price-tag of extra medication upfront.

Such an intensive strategy might be an option for younger patients who want to do everything they can to tackle their diagnosis, commented Ronald Tamler, MD, of the Mount Sinai Diabetes Center in New York City.

But the precise regimen used may not really be appealing in current practice, which is more conservative now than when the trial started both in terms of treatment targets under 7% A1c andpioglitazone after warnings about bladder cancer risk, Tamler noted.

Other practical concerns include the acceptability of a daily injectable drug in the regimen and polypharmacy, he added in an interview with MedPage Today.

Session moderator Julio Rosenstock, MD, of the Dallas Diabetes and Endocrine Center, likewise called the results controversial.

The trial included 155 drug-naive patients with newly-diagnosed type 2 diabetes randomized to open-label treatment strategy.

The combination group got doses ramped up to 2,000 mg of metformin, 30 mg pioglitazone, and 10 mcg exenatide once daily by the first month in the trial with a hemoglobin under 6.5% as the treatment target.

The comparison group got metformin at 1,000 mg per day that was stepped up to 2,000 mg at month 1, with the addition of glyburide at 5 mg daily if fasting glucose remained over 100 mg/dL.

At month 2, glyburide dose was doubled if glucose remained above 100 mg/dL or the A1c wasn't under the 6.5% target.

At month 3, insulin glargine was started at 10 units per day if those targets weren't met, with dose increased by 10 units on a weekly basis if glucose was over 100 mg/dL.

Visits went to an every 3-month schedule after the first 3 months and doses could be down titrated for hypoglycemia or its symptoms.

The combination therapy group brought the median hemoglobin A1c down to 5.8% compared with 6.4% in the conventional group.

Nearly all patients reached an A1c within the American Diabetes Association recommended threshold of 7.0% with the initial combination therapy strategy (92%), compared with 72% among the conventional group (P<0.001).

The combination strategy independently predicted 84% lower odds of failing to reach an A1c target under 6.5% on maximal therapy.

Twice as many combination-treated patient***** an A1c under 6.0% as did with the step-wise approach (60% versus 27%, P<0.001).

Body weight fell by 2.6 lb with the combination strategy but rose by 9.0 lb on conventional treatment over 24 months (-1.2 versus +4.1 kg, P<0.001).

The rate of hypoglycemia was 15% on triple therapy versus 46% on sequential therapy, which Tamler called not surprising based on the agents selected. Serious hypoglycemia requiring third-party assistance occurred in neither group.

GI adverse events were more common with the initial combination (33% versus 21%), while overall adverse event rates were similar between groups.

Limitations included what Tamler called an "apples to oranges" comparison of strategies that included different medications and the relatively small size.
 

原文链接：http://www.medpagetoday.com/MeetingCoverage/ADA/40042

编辑： belinda_1231    来源：丁香园