Liraglutide の体重減少降下、糖尿病発症遅延化?


LEAD-6 :リラグルチド vs バイエッタ GLP-1アゴニスト・ガチンコ対決(2009年 07月 07日) で、liraglutide(Novo Nordisk)とexenatide (Byetta, Amylin Pharmaceuticals)の直接比較

the heart.orgで・・・orlistat(Xenical, Roche)とliraglutide(Novo Nordisk)のガチンコ比較

Effects of Liraglutide in the Treatment of Obesity: A Randomized, Double-Blind, Placebo-Controlled Study

プラセボ -2.8Kg
Liraglutide 1.2mg -4.8Kg
Liraglutide 1.8mg -5.5Kg
Liraglutide 2.4mg -6.3Kg
Lireglutide 3mg  -7.2Kg
Orlistat -4.1Kg

肥満治療に対し作られた薬剤ですでに発売されているorlistat(Xenical, Roche)より、liraglutide(Novo Nordisk)の方が、肥満者に対する体重減少が認められた(Lancet 2009; DOI:10.1016/S0140-6736(09)61375-1.)。これは、liraglutideのようなGLP-1アナログの評価の最初の二重盲検プラセボ対照研究で、open-label比較

native GLP-1は1-2分と半減期短く、短期しか存在しないが、liraglutideは長期で13時間に及び、他のGLP-1アナログも糖尿病へのmarketを持つが、exenatide (Byetta, Amylin Pharmaceuticals)などは60-90分。


After a shaky FDA advisory panel meeting last Thursday, the Danish drug maker Novo Nordisk is entertaining new doubts about whether their most promising new diabetes drug liraglutide will receive timely FDA approval. An intense discussion about a rare form of thyroid cancer (medullary thyroid cancer) seen in mouse and rat studies seemed to unexpectedly pall the focus of the meeting, one of the first meetings to evaluate diabetes drugs under stricter new guidelines to rule out cardiovascular risk. The panel initially believed a few cases of a common thyroid tumor found in human clinical trials was insignificant, but when considered in light of the more serious type of thyroid tumors in rats and mice, the panel could not convincingly rule out the cancer risk.

Novo Nordisk Chief Scientific Officer Mads Krogsgaard Thomsen was indeed caught off-guard: “We knew we were going to discuss the issue, but we did not know [it was going to be] the overarching dominating thing.” The advisory panel was decidedly split (6-6 with 1 abstention) on whether the thyroid tumor risk should preclude the drug’s approval, and could not agree how to reliably assess the cancer risk. In the vote that was supposed to make headlines regarding whether there was sufficient data to rule out “unacceptable excess” cardiovascular risk, the panel voted 8-5 that the data was sufficient (not a hopeful sign either).

Liraglutideはまた血圧降下作用あり、1.8~3.0mg/dayで糖尿城前状態減少(84%-96%減少)を示した。モントリオールの2009年IDFのWorld Diabetes Congressで、ポスタープレゼンテーションを行いたのが後者の報告である。post hoc解析で、orlistatやプラセボ比較で有意に20週目の耐糖能正常オッズ比増加(p<0.01 all doses)



・ Astrup A, Rossner S, Van Gaal L, et al. Effects of liraglutide in the treatment of obesity: a randomized, double-blind, placebo-controlled study. Lancet 2009; DOI:10.1016/S0140-6736(09)61375-1.
・ Bray GA. Gastrointestinal hormones and weight management. Lancet 2009. DOI:10.1016/S0140-6736(09)61560-9.
・ Rucker D, Padwal R, Li SK, et al. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ 2008; 335: 1194-1199.
・Van Gaal L, Al Hakim M, Astrup A, et al. Liraglutide, a once-daily human GLP-1 analog, improves prediabetes status in obese subjects over 20 weeks: a randomized placebo-controlled trial. International Diabetes Federation 2009; October 18-22, 2009; Montreal, QC. Abstract D-0986.


by internalmedicine | 2009-10-26 10:03 | 糖尿病・肥満  

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