Osteoporosis Research Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Diabetes Obes Metab. 2012 Nov;14(11):990-9. doi: 10.1111/j.1463-1326.2012.01630.x. Epub 2012 Jun 29.
Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycaemia in patients with type 2 diabetes (T2DM) by increasing urinary glucose excretion. Owing to its mechanism of action, dapagliflozin could potentially affect the renal tubular transportation of bone minerals. Therefore, markers of bone formation and resorption and bone mineral density (BMD) were evaluated in patients with T2DM after 50 weeks of dapagliflozin treatment.
This international, multi-centre, randomized, parallel-group, double-blind, placebo-controlled study (ClinicalTrials.gov NCT00855166) enrolled patients with T2DM (women 55-75 years and men 30-75 years; HbA1c 6.5-8.5%; BMI ≥ 25 kg/m(2) ; body weight ≤ 120 kg) whose T2DM was inadequately controlled on metformin. One hundred and eighty-two patients 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 50, serum markers of bone formation (procollagen type 1 N-terminal propeptide; P1NP) and resorption (C-terminal cross-linking telopeptides of type I collagen; CTX), bone mineral density (BMD) as assessed by standardized Dual-Energy X-ray Absorptiometry (DXA) measurements and adverse events of fracture were evaluated as safety objectives.
One hundred and sixty-five patients (90.7%) completed the first 50 weeks. Compared with placebo, no significant changes from baseline in P1NP, CTX or BMD were identified over 50 weeks of dapagliflozin treatment, with no significant treatment-by-gender interactions. No fractures were reported.
Dapagliflozin had no effect on markers of bone formation and resorption or BMD after 50 weeks of treatment in both male and post-menopausal female patients whose T2DM was inadequately controlled on metformin.
达格列净是一种选择性钠-葡萄糖协同转运蛋白 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。由于其作用机制，达格列净可能会影响肾小管对骨矿物质的转运。因此，在接受达格列净治疗 50 周后，评估了 T2DM 患者的骨形成和骨吸收标志物以及骨密度（BMD）。
这是一项国际性、多中心、随机、平行分组、双盲、安慰剂对照研究（ClinicalTrials.gov NCT00855166），纳入了 T2DM 患者（女性 55-75 岁，男性 30-75 岁；糖化血红蛋白 6.5-8.5%；BMI≥25kg/m²；体重≤120kg），这些患者在二甲双胍治疗下血糖控制仍不理想。182 例患者被随机分为 1:1 组，分别接受达格列净 10mg/天或安慰剂治疗，联合开放标签二甲双胍治疗 24 周双盲治疗期，随后进行 78 周的站点和患者双盲扩展期。在第 50 周时，评估了血清骨形成标志物（I 型前胶原 N 端前肽；P1NP）和骨吸收标志物（I 型胶原 C 端交联肽；CTX）、通过标准化双能 X 射线吸收法（DXA）测量的骨密度（BMD）以及骨折不良事件，作为安全性目标。
165 例患者（90.7%）完成了前 50 周的治疗。与安慰剂相比，在接受达格列净治疗 50 周期间，P1NP、CTX 或 BMD 与基线相比均无显著变化，且无性别间的治疗差异。未报告骨折。
在二甲双胍控制不佳的 T2DM 男性和绝经后女性患者中，达格列净治疗 50 周后，对骨形成和骨吸收标志物或 BMD 没有影响。
