Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin
Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin
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DOI：
10.1111/dom.12189
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发表时间：
2014-02-01
影响因子：
5.8
通讯作者：
Parikh, S.
中科院分区：
文献类型：
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作者：
Bolinder, J.;Ljunggren, O.;Parikh, S.
AimsDapagliflozin是一种高选择性钠-葡萄糖共转运蛋白2 （SGLT2）抑制剂，通过增加尿糖排泄来降低2型糖尿病（T2DM）患者的高血糖和体重。在达格列净治疗102周后，对T2DM患者的长期血糖控制、体成分和骨安全性进行了评估。方法：该随机、双盲、安慰剂对照研究（NCT00855166）纳入T2DM患者[平均年龄：60.7岁；糖化血红蛋白7.2%;体重指数（BMI） 31.9 kg/m(2)；体重[91.5 kg]未充分控制二甲双胍。患者（N=182）随机按1:1分配，接受达格列净10mg /天或安慰剂加开放标签二甲双胍，为期24周的双盲治疗期，随后是78周的部位盲和患者盲延长期。在第102周，评估HbA1c、体重、腰围、双能x线吸收仪（DXA）测量的总体脂量、骨转换血清标志物、DXA测量的骨矿物质密度（BMD）和不良事件与基线的变化。结果140例患者（76.9%）完成研究。在102周内，达格列净治疗的患者HbA1c降低了-0.3%，体重降低了-4.54 kg，腰围降低了-5.0 cm，脂肪质量降低了-2.80 kg，而低血糖发生率没有增加。与安慰剂组相比，在102周内，骨转换或骨密度标记物与基线相比没有明显变化。两组各发生1例骨折。泌尿道感染（UTI）和生殖器感染的频率在两组治疗中相似。结论在102周内，达格列净改善了血糖控制，降低了体重和脂肪量，未影响二甲双胍控制不充分的T2DM患者的骨转换或骨密度指标。
AimsDapagliflozin, a highly selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycaemia and weight in patients with type2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. Long-term glycaemic control, body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment.MethodsThis randomized, double-blind, placebo-controlled study (NCT00855166) enrolled patients with T2DM [mean: age 60.7 years; HbA1c 7.2%; body mass index (BMI) 31.9 kg/m(2); body weight 91.5 kg] inadequately controlled on metformin. Patients (N=182) were randomly assigned 1:1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period. At week 102, changes from baseline in HbA1c, weight, waist circumference, total body fat mass as measured by dual-energy X-ray absorptiometry (DXA), serum markers of bone turnover, bone mineral density (BMD) as measured by DXA, and adverse events were evaluated.ResultsA total of 140 patients (76.9%) completed the study. Over 102 weeks, dapagliflozin-treated patients showed reductions in HbA1c by -0.3%, weight by -4.54 kg, waist circumference by -5.0 cm and fat mass by -2.80 kg without increase in rate of hypoglycaemia. Compared with placebo, no meaningful changes from baseline in markers of bone turnover or BMD were identified over 102 weeks. One fracture occurred in each treatment group. The frequency of urinary tract infection (UTI) and genital infection was similar in both treatment groups.ConclusionsOver 102 weeks, dapagliflozin improved glycaemic control, and reduced weight and fat mass, without affecting markers of bone turnover or BMD in patients with T2DM inadequately controlled on metformin.