Inzucchi Silvio E, Davies Melanie J, Khunti Kamlesh, Trivedi Prabhav, George Jyothis T, Zwiener Isabella, Johansen Odd Erik, Sattar Naveed
Yale University School of Medicine, New Haven, Connecticut, USA.
Diabetes Research Centre, University of Leicester, Leicester, UK.
Diabetes Obes Metab. 2021 Feb;23(2):425-433. doi: 10.1111/dom.14234. Epub 2020 Nov 20.
To investigate the association of different categories of baseline cardio-metabolic risk factors on the treatment effects of empagliflozin 10 and 25 mg when added as second-line therapy to metformin in patients with type 2 diabetes (T2D).
Patients aged 18 years or older with HbA1c 7.0%-10.0% were included. Analysis of covariance compared change from baseline to weeks 24 and 76 in HbA1c, body weight (BW) and systolic blood pressure (SBP) by respective baseline categories (HbA1c <8.5/≥8.5%; BW <80/80-90/>90 kg, SBP <130/130-140/>140 mmHg). Analyses were also conducted with a model using continuous covariates of cardio-metabolic factors.
In total, 637 patients (56.7% males; mean [SD] age 55.7 [9.9] years, HbA1c 7.9% [0.9%], BW 81.2 [18.8] kg, SBP 129.4 [14.6] mmHg) received one or more dose of either empagliflozin 10 mg (n = 217) or 25 mg (n = 213), or placebo (n = 207). At both time points, empagliflozin 10/25 mg versus placebo significantly (P < .0001) reduced HbA1c and BW, with greater reductions in HbA1c at higher baseline HbA1c (P interaction week 24/76 categorical and continuous models: .0290/.1431 and .0004/.0042, respectively) and in BW (P interaction .1340/.0012 and .0202/<.0001, respectively). Both empagliflozin doses also significantly lowered SBP versus placebo at both time points, with similar efficacy by subgroups of baseline SBP. Adverse events were consistent with the established empagliflozin safety profile across treatment groups.
Empagliflozin, as add-on to metformin, decreases HbA1c and BW, particularly in patients with higher HbA1c and BW baseline values, and effectively lowers SBP.
探讨2型糖尿病（T2D）患者在二甲双胍基础上联用恩格列净10mg和25mg作为二线治疗时，不同类别的基线心脏代谢危险因素与治疗效果之间的关联。
纳入年龄≥18岁、糖化血红蛋白（HbA1c）为7.0%-10.0%的患者。采用协方差分析，比较各基线类别（HbA1c<8.5%/≥8.5%；体重<80/80-90/>90kg，收缩压<130/130-140/>140mmHg）从基线至第24周和第76周时HbA1c、体重（BW）和收缩压（SBP）的变化。还使用心脏代谢因素的连续协变量模型进行分析。
共有637例患者（男性占56.7%；平均[标准差]年龄55.7[9.9]岁，HbA1c为7.9%[0.9%]，BW为81.2[18.8]kg，SBP为129.4[14.6]mmHg）接受了一剂或多剂恩格列净10mg（n=217）或25mg（n=213），或安慰剂（n=207）。在两个时间点，恩格列净10/25mg组与安慰剂组相比，HbA1c和BW均显著降低（P<.0001），基线HbA1c水平较高时HbA1c降低幅度更大（第24/76周分类和连续模型的P交互作用分别为0.0290/0.1431和0.0004/0.0042），体重降低幅度也更大（P交互作用分别为0.1340/0.0012和0.0202/<.0001）。两个恩格列净剂量组在两个时间点的SBP均较安慰剂组显著降低，不同基线SBP亚组的疗效相似。各治疗组的不良事件与已确立的恩格列净安全性特征一致。
恩格列净作为二甲双胍的附加治疗药物，可降低HbA1c和BW，尤其是在HbA1c和BW基线值较高的患者中，并且能有效降低SBP。
