利拉利汀对非裔2型糖尿病患者安全有效

费城(EGMN)——一项纳入226例非裔2型糖尿病患者的多中心、随机、安慰剂对照试验显示，利拉利汀治疗与高血糖显著改善相关。

 “非裔美国人一生中发生糖尿病的可能性增加77%，并且在临床试验中对降糖药物应答不佳，”美国小石城阿肯色糖尿病与内分泌中心的医学研究主管James R. Thrasher博士在美国临床内分泌医师协会年会上介绍，利拉利汀是一种每日用药1次的二肽基肽酶-4(DPP-4)抑制剂，已被批准用于治疗2型糖尿病。与其他DPP-4抑制剂不同，对于肾脏或肝脏受损患者不需调整利拉利汀的剂量。

该研究中，患者被随机分配至利拉利汀5 mg/d或安慰剂治疗24周。54%的患者为男性，平均年龄为54岁，平均体重指数为32.7 kg/m²。近2/3(72%)的患者有高血压。疗效分析集中包含接受利拉利汀治疗的100例患者和接受安慰剂的111例患者，利拉利汀和安慰剂组的基线糖化血红蛋白A_1c(HbA_1c)分别为8.6%和8.7%。多数患者已接受二甲双胍或一种磺脲类药物治疗，研究过程中这些治疗无变化。12%的患者未接受过任何治疗。

结果显示，24周时，利拉利汀和安慰剂组平均HbA1c分别降低了0.88%和0.24%，具有高度统计学差异(P=0.0002)。利拉利汀组达到HbA_1c低于7.0%的患者数是安慰剂组的3倍以上（28.0% vs. 8.7%），达到HbA_1c降幅≥0.5%的患者数接近安慰剂组的2倍（55.3% vs. 28.3%）。在纳入106例接受利拉利汀治疗的患者和120例接受安慰剂患者的安全性分析中，多数不良事件为轻度或中度，并且被视为与研究药物无关。最常见的不良事件为高血糖（利拉利汀组和安慰剂组发生率分别为2.8%和9.2%）和鼻咽炎（两组发生率分别为3.8%和5.0%）。利拉利汀组1例患者和安慰剂组2例患者发生严重不良事件。利拉利汀组3例患者和安慰剂组1例患者发生低血糖。无一事件需要外部辅助治疗。

Thrasher博士披露接受了勃林格殷格翰和礼来的研究资助，并且担任这两家公司的讲师，其中勃林格殷格翰是利拉利汀的生产商。

PHILADELPHIA (EGMN) – Linagliptin was associated with significant improvements in hyperglycemia in a multicenter, randomized, placebo-controlled, double-blind trial of 226 African-American patients with type 2 diabetes.

“African Americans have a 77% greater likelihood of developing diabetes yet tend to be underrepresented in clinical trials of antidiabetic drugs,” said Dr. James R. Thrasher, director of medical investigation at Arkansas Diabetes and Endocrinology Center, Little Rock. “We wanted to look at this group with higher rates of diabetes and higher risk for complications of diabetes.”

Linagliptin is a once-daily dipeptidyl peptidase-4 inhibitor, licensed for the treatment of type 2 diabetes. Unlike other DPP-4 inhibitors, it does not require dose adjustment for patients with renal or hepatic impairment, Dr. Thrasher noted in an interview at the annual meeting of the American Association of Clinical Endocrinologists.

Patients were randomized to 24 weeks of 5 mg/day linagliptin or placebo. Overall, 54% of the patients were men. The mean age was 54 years and mean body mass index was 32.7 kg/m². Nearly two-thirds (72%) had hypertension. In the efficacy analysis set of 100 linagliptin and 111 placebo patients, mean baseline hemoglobin A1c was 8.6% for the linagliptin group and 8.7% for the placebo group. Most patients were already taking metformin or a sulfonylurea, which did not change. Twelve percent were treatment naive.

By 24 weeks, mean HbA1c had dropped by 0.88 percentage points with linagliptin and 0.24 with placebo, a highly significant difference (P = 0.0002). Roughly three times more linagliptin patients achieved an HbA1c of less than 7.0% (28.0% vs. 8.7%) and almost twice as many had an HbA1c reduction of 0.5% or more (55.3% vs. 28.3%), Dr. Thrasher reported.

In the safety analysis set comprising 106 linagliptin and 120 placebo patients, most adverse events were mild or moderated and were considered unrelated to the study drug. The most common of these were hyperglycemia (2.8% in the linagliptin group and 9.2% in the placebo group) and nasopharyngitis (3.8% and 5.0%, respectively). Serious adverse events were reported in one linagliptin patient and two placebo patients. Hypoglycemia occurred in three linagliptin patients and one placebo patient. No event required external assistance, he said.

The responses among the African Americans in this study were comparable to those seen in the pivotal trials for linagliptin. “We know from studies of blood pressure medications that African Americans respond differently to different medications. In the area of diabetes, this is kind of landmark. It’s something new for us to look at ethnic groups specifically with a clinical trial for a drug. ... I hope this opens up the door to more [such] research with other drugs,” Dr. Thrasher said.

Dr. Thrasher disclosed that he has received research grants and is a speaker for Boehringer Ingelheim, which manufactures linagliptin, and Lilly.