Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of Chinese Ministry of Health, Shanghai, China.
Seth Gordhandas Sunderdas, Medical College and King Edward Memorial Hospital, Mumbai, India.
Adv Ther. 2017 Sep;34(9):2150-2162. doi: 10.1007/s12325-017-0595-7. Epub 2017 Aug 17.
Asian patients with type 2 diabetes (T2D) are younger, leaner, and more likely to develop renal dysfunction than White populations. In this multiethnic analysis of data from phase 3 trials, we investigated the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in Asians stratified by these subphenotypes.
Data from randomized, double-blind, placebo-controlled trials evaluating linagliptin (as monotherapy, add-on therapy to metformin ± sulfonylurea, combined with pioglitazone or added to insulin) were pooled with efficacy data from 11 randomized trials of at least 24 weeks and safety data from 15 trials of various durations.
In the efficacy set, 1404 Asian patients received linagliptin [mean (standard deviation) age 54.5 (10.1) years; body mass index (BMI) 26.0 (3.9) kg/m] and 661 received placebo [age 55.0 (9.7) years; BMI 26.1 (3.9) kg/m] with the same glycated hemoglobin (HbA1c): 8.2 (0.9)% in both groups. At 24 weeks, the placebo-corrected adjusted mean ± standard error change from baseline in HbA1c with linagliptin was -0.73 ± 0.04% (95% confidence interval -0.81, -0.65; P < 0.0001). Reductions in HbA1c were similar upon stratification by age [<65 years, -0.71 ± 0.05% (-0.80, -0.62; P < 0.0001); ≥65 years, -0.81 ± 0.10% (-1.01, -0.60; P < 0.0001)], BMI (<25 kg/m, -0.82 ± 0.06% [-0.94, -0.70; P < 0.0001]; ≥25 kg/m, -0.65 ± 0.06% [-0.76, -0.54; P < 0.0001]) and estimated glomerular filtration rate [<90 mL/min/1.73 m, -0.71 ± 0.06% (-0.82, -0.60; P < 0.0001); ≥90 mL/min/1.73 m, -0.75 ± 0.06% (-0.87, -0.64; P < 0.0001)]. In the safety set (linagliptin, n = 1842; placebo, n = 839), 52.2% and 54.6% of patients, respectively, experienced adverse events. The rates of drug-related adverse events were 10.9% in the linagliptin group and 10.4% in the placebo group. The respective rates of hypoglycemia were 8.3% and 9.5%, mainly among patients treated with sulfonylurea or insulin. Severe hypoglycemia was rare (<1.0% in either group).
Linagliptin effectively reduced hyperglycemia in Asian patients with uncontrolled T2D, irrespective of age, BMI, renal function, or ethnic subgroups, and was well tolerated.
Boehringer Ingelheim, Eli Lilly and Company, and the Diabetes Alliance.
与白人人群相比，亚洲 2 型糖尿病（T2D）患者更年轻、更瘦，且更容易出现肾功能障碍。在这项来自 3 期临床试验的多中心分析中，我们根据这些亚表型，研究了二肽基肽酶-4 抑制剂利拉利汀在亚洲人群中的疗效和安全性。
汇总了评估利拉利汀（单药治疗、二甲双胍±磺酰脲类药物的联合治疗、与吡格列酮联合或添加胰岛素）的随机、双盲、安慰剂对照试验的疗效数据，以及来自 11 项至少 24 周的随机试验和 15 项不同持续时间的安全性数据。
在疗效组中，1404 例亚洲患者接受利拉利汀治疗[平均（标准差）年龄 54.5（10.1）岁；体重指数（BMI）26.0（3.9）kg/m]，661 例患者接受安慰剂治疗[年龄 55.0（9.7）岁；BMI 26.1（3.9）kg/m]，糖化血红蛋白（HbA1c）相同，两组均为 8.2（0.9）%。24 周时，利拉利汀治疗组与安慰剂组相比，HbA1c 的安慰剂校正平均变化值±标准误差为-0.73±0.04%（95%置信区间-0.81，-0.65；P<0.0001）。根据年龄分层[<65 岁，-0.71±0.05%（-0.80，-0.62；P<0.0001）；≥65 岁，-0.81±0.10%（-1.01，-0.60；P<0.0001）]、BMI（<25 kg/m，-0.82±0.06%（-0.94，-0.70；P<0.0001）；≥25 kg/m，-0.65±0.06%（-0.76，-0.54；P<0.0001）]和估计肾小球滤过率[<90 mL/min/1.73 m，-0.71±0.06%（-0.82，-0.60；P<0.0001）；≥90 mL/min/1.73 m，-0.75±0.06%（-0.87，-0.64；P<0.0001）]，HbA1c 降低情况相似。在安全性组（利拉利汀，n=1842；安慰剂，n=839）中，分别有 52.2%和 54.6%的患者发生不良事件。利拉利汀组药物相关不良事件发生率为 10.9%，安慰剂组为 10.4%。两组的低血糖发生率分别为 8.3%和 9.5%，主要发生在接受磺酰脲类药物或胰岛素治疗的患者中。严重低血糖症很少见（两组均<1.0%）。
利拉利汀有效降低了未控制的 2 型糖尿病亚洲患者的高血糖，无论年龄、BMI、肾功能或亚组种族如何，且耐受性良好。
勃林格殷格翰、礼来公司和糖尿病联盟。
