Dallas Diabetes Research Center at Medical City, Dallas, Texas.
National Research Institute, Los Angeles, California.
Diabetes Obes Metab. 2018 Mar;20(3):520-529. doi: 10.1111/dom.13103. Epub 2017 Oct 2.
We evaluated the efficacy and safety of ertugliflozin, an SGLT2 inhibitor, in type 2 diabetes mellitus (T2DM) inadequately controlled (HbA1c, 7.0%-10.5%) with metformin monotherapy (≥1500 mg/d for ≥8 weeks).
This was a double-blind, 26-week, multicentre study with ongoing 78-week extension (ClinicalTrials.gov identifier: NCT02033889). A total of 621 participants were randomized 1:1:1 to placebo, or ertugliflozin 5 or 15 mg/d. The primary endpoint was change from baseline at week 26 in HbA1c. Secondary efficacy endpoints were change from baseline at week 26 in fasting plasma glucose (FPG), body weight, systolic/diastolic blood pressure (SBP/DBP) and number of participants with HbA1c <7.0% (53 mmol/mol). Pre-specified adverse events (AEs) of special interest and percent change from baseline in bone mineral density (BMD) were also assessed at week 26.
At week 26, the placebo-adjusted least-squares mean change from baseline HbA1c (8.1%) was -0.7% and -0.9% for ertugliflozin 5 and 15 mg, respectively (both P < .001), to final means of 7.3% and 7.2%, respectively. The odds of HbA1c <7.0% were significantly greater in both ertugliflozin groups vs placebo. Ertugliflozin significantly reduced FPG, body weight, SBP and DBP vs placebo. The incidence of genital mycotic infections was higher in the ertugliflozin groups (female subjects: placebo, 0.9%; ertugliflozin 5 mg, 5.5%; ertugliflozin 15 mg, 6.3% [P = .032]; male subjects: 0%; 3.1%; 3.2%, respectively), as was the incidence of urinary tract infections and symptomatic hypoglycaemia. The incidence of hypovolaemia AEs was similar across groups. Ertugliflozin had no adverse impact on BMD at week 26.
Ertugliflozin added to metformin in patients with inadequately controlled T2DM improved glycaemic control, reduced body weight and BP, but increased the incidence of genital mycotic infections.
我们评估了 SGLT2 抑制剂依格列净在二甲双胍单药治疗（≥1500mg/d，至少 8 周）控制不佳的 2 型糖尿病（T2DM）患者中的疗效和安全性（HbA1c，7.0%-10.5%）。
这是一项为期 26 周的双盲、多中心研究，同时进行了 78 周的扩展（ClinicalTrials.gov 标识符：NCT02033889）。共有 621 名参与者按 1:1:1 的比例随机分配至安慰剂组或依格列净 5mg/d 或 15mg/d 组。主要终点为 26 周时与基线相比的 HbA1c 变化。次要疗效终点为 26 周时与基线相比的空腹血糖（FPG）、体重、收缩压/舒张压（SBP/DBP）和 HbA1c＜7.0%（53mmol/mol）的参与者比例。还在第 26 周评估了预先指定的特别关注不良事件（AE）和骨密度（BMD）的基线百分比变化。
在第 26 周时，安慰剂调整后的最小二乘均数基线 HbA1c（8.1%）变化分别为依格列净 5mg 和 15mg 组的-0.7%和-0.9%（均 P＜0.001），最终平均值分别为 7.3%和 7.2%。与安慰剂相比，依格列净 5mg 和 15mg 组的 HbA1c＜7.0%的可能性显著更高。与安慰剂相比，依格列净显著降低了 FPG、体重、SBP 和 DBP。依格列净组女性患者（女性受试者：安慰剂组为 0.9%；依格列净 5mg 组为 5.5%；依格列净 15mg 组为 6.3%[P=0.032]；男性受试者：0%；3.1%；3.2%，分别）和男性患者（0%；3.1%；3.2%，分别）的生殖器真菌感染发生率更高，尿路感染和症状性低血糖的发生率也更高。各组低血容量相关 AE 的发生率相似。依格列净对第 26 周的 BMD 无不良影响。
在二甲双胍控制不佳的 T2DM 患者中，依格列净联合二甲双胍治疗可改善血糖控制，降低体重和血压，但增加了生殖器真菌感染的发生率。
