I.G. - Endocrinologie, Campus Gasthuisberg, Leuven, Belgium.
Int J Clin Pract. 2013 Oct;67(10):947-56. doi: 10.1111/ijcp.12252. Epub 2013 Aug 21.
Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale 'pragmatic' trials.
EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA(1c) > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA(1c) < 7% without hypoglycaemia or ≥ 3% increase in body weight.
In this large group of T2DM patients, a second OAD was added at mean HbA(1c) of 8.2 ± 1.3%, with no baseline HbA(1c) difference between cohorts. Second-line OAD therapy attained the PEP in the majority of patients, with higher attainment in those prescribed a vildagliptin-based regimen. The adjusted odds ratio was 1.49 (95% CI: 1.42, 1.55; p < 0.001). In patients with baseline HbA(1c) ≥ 7%, SEP 3 was achieved by 35% of patients on a vildagliptin-based combination and by 23% of those receiving comparator combinations. The adjusted odds ratio was 1.96 (95% CI: 1.85, 2.07; p < 0.001). Safety events were reported infrequently and safety profiles of vildagliptin and other OADs were consistent with previous data.
EDGE demonstrates that in a 'real-life' setting, vildagliptin as second OAD can lower HbA(1c) to target without well-recognised OAD side effects, more frequently than comparator OADs. In addition, EDGE illustrates that conducting large-scale, prospective, real-life studies poses challenges but yields valuable clinical information complementary to RCTs.
需要真实世界的研究来证实随机对照试验（RCT）结果的临床相关性。本研究旨在评估维格列汀添加治疗与其他口服降糖药（OAD）添加到 OAD 单药治疗在真实环境中的有效性和耐受性，并探讨大规模“实用”试验的优势和局限性。
EDGE 是一项前瞻性、为期 1 年、全球性的真实世界观察性研究，2957 名医生报告了在 OAD 单药治疗未能达到血糖目标的 45868 例 2 型糖尿病患者中，二线 OAD 的治疗效果。医生可以添加任何 OAD，患者进入维格列汀或（汇总）对照队列。主要有效性和耐受性终点（PEP）评估了 HbA1c 降低>0.3%、无低血糖、体重增加、外周水肿或胃肠道副作用的患者比例。最具临床相关性的次要终点（SEP3）是在无低血糖或体重增加≥3%的情况下达到终点 HbA1c<7%。
在这一大组 2 型糖尿病患者中，二线 OAD 在平均 HbA1c 为 8.2±1.3%时添加，两组患者基线 HbA1c 无差异。大多数患者达到了 PEP，使用维格列汀为基础的治疗方案的患者达到 PEP 的比例更高。调整后的优势比为 1.49（95%CI：1.42，1.55；p<0.001）。在基线 HbA1c≥7%的患者中，维格列汀为基础的联合治疗组有 35%的患者达到 SEP3，而接受对照联合治疗组有 23%的患者达到 SEP3。调整后的优势比为 1.96（95%CI：1.85，2.07；p<0.001）。不良事件报告频率较低，维格列汀和其他 OAD 的安全性与先前数据一致。
EDGE 表明，在“真实世界”环境中，作为二线 OAD 的维格列汀可以在不产生公认的 OAD 副作用的情况下降低 HbA1c 至目标值，其频率高于对照 OAD。此外，EDGE 表明，进行大规模、前瞻性、真实世界的研究具有挑战性，但可以提供有价值的临床信息，补充 RCT 的结果。
