Effects of Dapagliflozin on Body Weight, Total Fat Mass, and Regional Adipose Tissue Distribution in Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Metformin
Effects of Dapagliflozin on Body Weight, Total Fat Mass, and Regional Adipose Tissue Distribution in Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Metformin
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DOI：
10.1210/jc.2011-2260
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发表时间：
2012-03-01
影响因子：
5.8
通讯作者：
Parikh, Shamik
中科院分区：
文献类型：
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作者：
Bolinder, Jan;Ljunggren, Osten;Parikh, Shamik
内容：达格列净是一种选择性钠-葡萄糖协同转运蛋白2（SGLT 2）抑制剂，通过增加尿糖排泄降低2型糖尿病（T2 DM）患者的高血糖，体重减轻是一项一致的相关发现。目的：我们的目的是确认使用达格列净的体重减轻，并通过身体组成测量确定体重减轻是否由脂肪或液体组分的变化引起。设定：这是一项为期24周、国际性、多中心、随机、平行组、双盲、安慰剂对照研究，在5个国家的40个研究中心进行了为期78周的研究中心和患者设盲扩展期。（平均值：女性63.3岁，男性58.6岁;血红蛋白A1 c 7.17%，体重指数31.9 kg/m2，体重91.5 kg）二甲双胍控制不佳。干预：Dapagliflozin 10 mg/d或安慰剂添加到开放标签二甲双胍为24 wk.Main结局措施：主要终点是总体重（TBW）从基线在第24周的变化。关键次要终点为第24周时腰围和双能X线吸收法总体脂量（FM）较基线的变化，以及第24周时体重减轻至少5%的患者比例。结果：在wk 24，用达格列净的安慰剂校正的变化如下：TBW，-2.08 kg [95%置信区间（CI）= -2.84 to -1.31; P < 0.0001];腰围，-1.52 cm（95% CI = -2.74至-0.31; P = 0.0143）; FM，-1.48 kg（95% CI = -2.22至-0.74; P = 0.0001）;体重减轻至少5%的患者比例，+26.2%（95% CI = 15.5至36.7; P < 0.0001）; VAT，-258.4 cm（3）（95% CI = -448.1至-68.6;标称P = 0.0084）; SAT，-184.9 cm（3）（95% CI = -359.7至-10.1;标称P = 0.0385）。在达格列净组和安慰剂组中，严重不良事件的报告率分别为6.6%和1.1%;提示外阴阴道炎、龟头炎和相关生殖器感染的事件的报告率分别为3.3%和0%;下尿路感染的报告率分别为6.6%和2.2%。结论：在二甲双胍控制不佳的T2 DM患者中，达格列净主要通过降低FM、VAT和SAT来降低TBW。（临床内分泌代谢杂志97：1020-1031，2012）
Context: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding.Objectives: Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components.Design and Setting: This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries.Patients: Included were 182 patients with T2DM (mean values: women 63.3 and men 58.6 yr of age; hemoglobin A1c 7.17%, body mass index 31.9 kg/m(2), and body weight 91.5 kg) inadequately controlled on metformin.Intervention: Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk.Main Outcome Measures: Primary endpoint was total body weight (TBW) change from baseline at wk 24. Key secondary endpoints were waist circumference and dual-energy x-ray absorptiometry total-body fat mass (FM) changes from baseline at wk 24, and patient proportion achieving body weight reduction of at least 5% at wk 24. In a subset of patients, magnetic resonance assessment of visceral adipose tissue (VAT) and sc adipose tissue (SAT) volume and hepatic lipid content were also evaluated.Results: At wk 24, placebo-corrected changes with dapagliflozin were as follows: TBW, -2.08 kg [95% confidence interval (CI) = -2.84 to -1.31; P < 0.0001]; waist circumference, -1.52 cm(95% CI = -2.74 to -0.31; P = 0.0143); FM, -1.48 kg (95% CI = -2.22 to -0.74; P = 0.0001); proportion of patients achieving weight reduction of at least 5%, +26.2% (95% CI = 15.5 to 36.7; P < 0.0001); VAT, -258.4 cm(3) (95% CI = -448.1 to -68.6; nominal P = 0.0084); SAT, -184.9 cm(3) (95% CI = -359.7 to -10.1; nominal P = 0.0385). In the dapagliflozin vs. placebo groups, respectively, serious adverse events were reported in 6.6 vs. 1.1%; events suggestive of vulvovaginitis, balanitis, and related genital infection in 3.3 vs. 0%; and lower urinary tract infections in 6.6 vs. 2.2%.Conclusions: Dapagliflozin reduces TBW, predominantly by reducing FM, VAT and SAT in T2DM inadequately controlled with metformin. (J Clin Endocrinol Metab 97: 1020-1031, 2012)