Cook William, Minervini Gianmaria, Bryzinski Brian, Hirshberg Boaz
AstraZeneca, Wilmington, DE.
Postgrad Med. 2014 Oct;126(6):19-32. doi: 10.3810/pgm.2014.10.2818.
To test the effectiveness and safety of saxagliptin 5 mg/d in patients with type 2 diabetes mellitus (T2DM) with and without history of cardiovascular disease (CVD) or cardiovascular (CV) risk factors.
The authors conducted a post hoc analysis of data from 3 randomized studies that compared saxagliptin versus placebo as initial combination therapy with metformin for 24 weeks (N = 648) and versus placebo as an add-on to insulin with and without metformin for 24 weeks (N = 455), and assessed noninferiority to glipizide as an add-on to metformin for 52 weeks (N = 858). Efficacy outcomes were the adjusted mean change from baseline in glycated hemoglobin (HbA1c) level, fasting plasma glucose concentration, and body weight and the proportion of patients achieving an HbA1c level < 7%. Pairwise comparisons were performed in subgroups with 1) history/no history of CVD, 2) ≥ 2 versus 0 to 1 CV risk factors, 3) hypertension/no hypertension, and 4) statin use/no statin use. Adverse events (AE) and hypoglycemia were monitored.
In the initial combination therapy study, reductions in HbA1c level from baseline were greater with saxagliptin versus placebo in all subgroups (difference [saxagliptin - placebo], -0.38% to -0.67%). In the add-on to insulin ± metformin study, differences in adjusted mean change in HbA1c level versus placebo ranged from -0.23% to -0.58% across subgroups. In the noninferiority to glipizide study, adjusted mean changes in HbA1c level were comparable between saxagliptin and glipizide, across subgroups (difference, 0.08%-0.21%). No evidence suggested clinically relevant treatment-by-subgroup interactions in pairwise comparison. Incidences of ≥ 1 AE were comparable across subgroups. Incidences of confirmed hypoglycemia with saxagliptin were 0 in both metformin add-on studies and 1.2% to 7.8% with saxagliptin + insulin ± metformin.
In patients with T2DM, saxagliptin 5 mg/d was similarly effective in improving glycemic control, with an AE profile similar to that of placebo, irrespective of CVD history, number of CV risk factors, hypertension, or statin use.
www.ClinicalTrials.gov identifiers: NCT00327015, NCT00575588, NCT00757588.
在有或无心血管疾病（CVD）病史或心血管（CV）危险因素的2型糖尿病（T2DM）患者中，测试5毫克/天的沙格列汀的有效性和安全性。
作者对3项随机研究的数据进行了事后分析，这些研究比较了沙格列汀与安慰剂作为二甲双胍初始联合治疗24周（N = 648），以及与安慰剂作为胰岛素加或不加二甲双胍的附加治疗24周（N = 455），并评估了沙格列汀作为二甲双胍附加治疗52周（N = 858）时相对于格列吡嗪的非劣效性。疗效指标包括糖化血红蛋白（HbA1c）水平、空腹血糖浓度和体重相对于基线的调整后平均变化，以及HbA1c水平<7%的患者比例。在以下亚组中进行了两两比较：1）有/无CVD病史；2）≥2个与0至1个CV危险因素；3）有高血压/无高血压；4）使用他汀类药物/未使用他汀类药物。监测不良事件（AE）和低血糖情况。
在初始联合治疗研究中，在所有亚组中，沙格列汀组的HbA1c水平相对于基线的降低幅度均大于安慰剂组（差异[沙格列汀-安慰剂]，-0.38%至-0.67%）。在胰岛素±二甲双胍附加治疗研究中，各亚组中HbA1c水平相对于安慰剂的调整后平均变化差异为-0.23%至-0.58%。在相对于格列吡嗪的非劣效性研究中，各亚组中沙格列汀和格列吡嗪的HbA1c水平调整后平均变化相当（差异为0.08%-0.21%）。两两比较中没有证据表明存在具有临床意义的亚组治疗交互作用。各亚组中≥1次AE的发生率相当。在两项二甲双胍附加治疗研究中，沙格列汀导致的确诊低血糖发生率均为0，而在沙格列汀+胰岛素±二甲双胍治疗中为1.2%至7.8%。
在T2DM患者中，无论CVD病史、CV危险因素数量、高血压或他汀类药物使用情况如何，5毫克/天的沙格列汀在改善血糖控制方面同样有效，且AE情况与安慰剂相似。
www.ClinicalTrials.gov标识符：NCT00327015、NCT00575588、NCT00757588。
