Early Phase Clinical Unit - Berlin, Parexel International GmbH, Klinikum Westend - Haus 18, Spandauer Damm 130, 14050 Berlin, Germany.
Novartis Pharmaceuticals Corporation, Florham Park, NJ, USA.
Diabetes Res Clin Pract. 2014 Mar;103(3):458-65. doi: 10.1016/j.diabres.2013.12.011. Epub 2013 Dec 25.
Pasireotide, a multireceptor-targeted somatostatin analogue with efficacy in Cushing's disease and acromegaly, can affect glucose metabolism due to inhibition of insulin secretion and incretin hormone responses. A study was therefore conducted to evaluate different antihyperglycemic drugs in the management of pasireotide-associated hyperglycemia.
This was a 1-week, Phase I, open-label study. Healthy male volunteers were randomized to pasireotide 600 μg sc bid alone or co-administered with metformin 500 mg po bid, nateglinide 60 mg po tid, vildagliptin 50mg po bid, or liraglutide 0.6 mg sc qd. An oral glucose tolerance test (OGTT) was performed on days 1 and 7 to evaluate effects on serum insulin, plasma glucose and glucagon levels. Safety/tolerability and pharmacokinetic effects were also evaluated.
Ninety healthy male volunteers were enrolled (n=18 per arm). After 7 days of treatment, plasma glucose AUC post-OGTT increased by 69% with pasireotide alone. The effect was reduced by 13%, 29%, 45% and 72% with co-administration of metformin, nateglinide, vildagliptin and liraglutide, respectively. On day 7, compared with pasireotide alone, the decrease in serum insulin was attenuated with nateglinide, metformin, liraglutide and vildagliptin co-administration (levels were 3%, 6%, 34% and 71% higher, respectively). Minimal changes in plasma glucagon were observed. Adverse events were consistent with the safety profiles of the drugs used.
Vildagliptin and liraglutide were most effective in minimizing pasireotide-associated hyperglycemia in healthy volunteers.
帕瑞肽是一种多受体靶向生长抑素类似物，对库欣病和肢端肥大症有效，由于抑制胰岛素分泌和肠促胰岛素激素反应，它可能会影响葡萄糖代谢。因此，进行了这项研究以评估不同的抗高血糖药物在帕瑞肽相关高血糖症的治疗中的作用。
这是一项为期 1 周、I 期、开放性标签研究。健康男性志愿者随机分为帕瑞肽 600μg 皮下注射，每天 2 次，或与二甲双胍 500mg 口服，每天 2 次，那格列奈 60mg 口服，每天 3 次，维格列汀 50mg 口服，每天 2 次，或利拉鲁肽 0.6mg 皮下注射，每天 1 次联合治疗。在第 1 天和第 7 天进行口服葡萄糖耐量试验（OGTT），以评估对血清胰岛素、血浆葡萄糖和胰高血糖素水平的影响。还评估了安全性/耐受性和药代动力学效应。
共纳入 90 名健康男性志愿者（每组 18 名）。帕瑞肽单用时，OGTT 后血浆葡萄糖 AUC 增加 69%。与帕瑞肽联合使用时，二甲双胍、那格列奈、维格列汀和利拉鲁肽分别使这种作用降低了 13%、29%、45%和 72%。第 7 天，与帕瑞肽单用时相比，那格列奈、二甲双胍、利拉鲁肽和维格列汀联合使用时，血清胰岛素的下降得到缓解（水平分别升高了 3%、6%、34%和 71%）。血浆胰高血糖素仅有微小变化。不良事件与所用药物的安全性特征一致。
在健康志愿者中，维格列汀和利拉鲁肽在最小化帕瑞肽相关高血糖方面最有效。
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