Enhanced Weight Loss Following Coadministration of Pramlintide With Sibutramine or Phentermine in a Multicenter Trial
Enhanced Weight Loss Following Coadministration of Pramlintide With Sibutramine or Phentermine in a Multicenter Trial
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DOI：
10.1038/oby.2009.478
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发表时间：
2010-09-01
期刊：
影响因子：
6.9
通讯作者：
Shen, Larry Z.
中科院分区：
文献类型：
--
作者：
Aronne, Louis J.;Halseth, Amy E.;Shen, Larry Z.
临床前证据表明，使用针对不同调节途径的药物组合进行肥胖药物治疗可能会对体重减轻产生强大的累加或协同作用。这项随机安慰剂对照试验检查了胰淀素类似物普兰林肽单独使用或与芬特明或西布曲明联合使用的安全性和有效性。所有患者均接受生活方式干预。在为期1周的安慰剂导入期后，244名肥胖或超重、非糖尿病受试者（88%女性; 41 ± 11岁; BMI 37.7 ± 5.4 kg/m2;体重103 ± 19 kg;平均值± s.d.）接受安慰剂皮下（sc）t.i.d.，普兰林肽SC（120 μ g每日3次），普兰林肽sc（120 μ g t.i.d.）+ 口服西布曲明（10 mg q. a.m.），或普兰林肽sc（120 μ g t.i.d.）+ 口服芬特明（37.5 mg q. a.m.）24周对于仅接受皮下给药的受试者，治疗为单盲，对于联合治疗组的受试者，治疗为开放标签。第24周时，任一联合治疗组的体重减轻均大于普兰林肽单独治疗组或安慰剂组（P < 0.001;普兰林肽+西布曲明组为11.1 ± 1.1%，普兰林肽+芬特明组为11.3 ± 0.9%，普兰林肽组为-3.7 ± 0.7%;安慰剂组为-2.2 ± 0.7%;平均值± s.e.）。普兰林肽+西布曲明组心率和舒张压均较基线升高（3.1 ± 1.2次/分，P < 0.05; 2.7 ± 0.9 mm Hg，P < 0.01）和普兰林肽+芬特明（4.5 +/- 1.3次/分，P < 0.01; 3.5 +/- 1.2 mm Hg，P < 0.001）。然而，接受这些治疗的大多数受试者的血压保持在正常范围内。这些结果支持含普兰林肽的组合治疗肥胖症的潜力。
Preclinical evidence suggests that pharmacotherapy for obesity using combinations of agents targeted at distinct regulatory pathways may produce robust additive or synergistic effects on weight loss. This randomized placebo-controlled trial examined the safety and efficacy of the amylin analogue pramlintide alone or in combination with either phentermine or sibutramine. All patients also received lifestyle intervention. Following a 1-week placebo lead-in, 244 obese or overweight, nondiabetic subjects (88% female; 41 +/- 11 years; BMI 37.7 +/- 5.4 kg/m(2); weight 103 +/- 19 kg; mean +/- s.d.) received placebo subcutaneously (sc) t.i.d., pramlintide sc (120 mu g t.i.d.), pramlintide sc (120 mu g t.i.d.) + oral sibutramine (10 mg q.a.m.), or pramlintide sc (120 mu g t.i.d.) + oral phentermine (37.5 mg q.a.m.) for 24 weeks. Treatment was single-blind for subjects receiving subcutaneous medication only and open-label for subjects in the combination arms. Weight loss achieved at week 24 with either combination treatment was greater than with pramlintide alone or placebo (P < 0.001; 11.1 +/- 1.1% with pramlintide + sibutramine, 11.3 +/- 0.9% with pramlintide + phentermine, -3.7 +/- 0.7% with pramlintide; -2.2 +/- 0.7% with placebo; mean +/- s.e.). Elevations from baseline in heart rate and diastolic blood pressure were demonstrated with both pramlintide + sibutramine (3.1 +/- 1.2 beats/min, P < 0.05; 2.7 +/- 0.9 mm Hg, P < 0.01) and pramlintide + phentermine (4.5 +/- 1.3 beats/min, P < 0.01; 3.5 +/- 1.2 mm Hg, P < 0.001) using 24-h ambulatory monitoring. However, the majority of subjects receiving these treatments remained within normal blood pressure ranges. These results support the potential of pramlintide-containing combination treatments for obesity.