西布曲明对肥胖患者糖脂代谢、体脂及胰岛素抵抗影响的多中心研究

Effects of sibutramine on blood glucose and lipids, body fat mass and insulin resistance in obese patients: a multi-center clinical trial

目的观察减重药西布曲明对肥胖患者糖脂代谢、全身总脂量、腹内脂肪(IAFA)及胰岛素抵抗(IR)的影响。方法采用随机双盲双模拟、安慰剂对照、多中心临床试验。359例不伴高血压和糖尿病,体重指数≥27kg/m2的肥胖患者被随机分入西布曲明片或胶囊组或安慰剂组。西布曲明初始剂量为10mg/d,疗效不明显者加至20mg/d,疗程24周。结果西布曲明片和胶囊组治疗前后平均体重分别减轻4·86kg和4·68kg(P<0·05),空腹血糖及血脂有一定改善,HOMA-IR指数分别由5·32和5·09降至3·32和3·12(P<0·05);全身总脂量分别减少4·07kg和4·09kg(P<0·05),IAFA分别减少19·21%和16·98%(P<0·05);上述指标在安慰剂组改变不如西布曲明组明显。结论西布曲明有一定的纠正肥胖者糖脂代谢紊乱,减少脂肪特别是IAFA的作用,在一定程度上减轻IR。

Objective To evaluate the effects of sibutramine on body weight, body fat mass, metabolism of plasma glucose and serum lipids, and insulin resistance （IR） in primary obesity patients. Methods A double-blind, double-placebo, randomized controlled, multi-center clinical trial was conducted. 359 voluntary obese subjects, whose body mass index （BMI） ≥27 kg/m^2, without hypertention and diabetes, were enrolled. They were randomly divided into group A, B and C respectively. Sibutramine tablets or capsules were administered 10-20 mg/day for 24 weeks to the test groups and placebo to a control group. CT scan was used to measure the intra or subcutaneous-abdominal fat areas （ IAFA, SAFA） at L4-L5 level. Dual energy X-ray absorptiometry （DEXA） was used to measure total body fat mass （TBFM）. Results 315 subjects continued to be followed for 24 weeks. After opening the blind, it was shown that group A received sibutramine tablet （n = 107）, group B placebo （n = 104） and group C was capsule （n = 104）. In group A and C body weight loss was 4. 86 kg （6. 42% ） and 4.68 kg （6. 38% ）, TBFM reduction was 4. 07 kg （ 13.94% ） and 4.09 kg（ 15.02% ）, SAFA decreased 7. 30% and 7.45%, IAFA decreased 19. 21% and 16. 98% respectively. Fasting plasma glucose decreased from 5. 69 to 4. 83 mmol/L and from 5.38 to 4. 69 mmol/L in group A and C respectively. Fasting serum insulin decreased from 20. 98 to 14.75 mU/L and from 21.11 to 14.68 mU/L, 2 h insulin decreased from 70.91 to 44.11 mU/L and from 73.13 to 41.93 mU/L in group A and C respectively. Serum triglyceride decreased from 1.98 to 1.73 mmol/L and 1.84 to 1.67 retool/L, total cholesterol decreased from 5.08 to 4. 75 mmol/L and from 5. 06 to 4. 46 rental/L, high-density lipoprotein cholesterol increased from 1.13 to 1.28 mmol/L and 1.10 to 1.31 mmol/L in group A and C respectively, HOMA-IR index decreased from 5. 32 to 3. 32, and from 5.09 to 3.12 respectively in group A and C. Adverse drug reaction was 32.41%, 13.47% and 31.20% in group A, B and C. Conclusions Sibutramine tablet or capsule decreases comparably body weight and TBFM, especially IAFA regulates plasma glucose and serum lipid metabolism and also decreases IR. Sibutramine is well tolerated in most of the subjects.