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 選択的セロトニン5-HT2c受容体アゴニストのロルカセリンlorcaserinが、体重減少に効果があるかもしれないという報告。これまでの体重減少薬fenfluramineやdexfenfluramineは、受容体の選択性が低く、肺高血圧症などのリスクがあった。

 二重盲検臨床試験で、3182人の肥満成人(BMI値平均は36.2)に対し、ロルカセリン(10mgx2/day)あるいはプラセボを52週間投与。52週後、プラセボ群にはプラセボを投与し続け、ロルカセリン群にはランダムにロルカセリンあるいはプラセボを投与。主要アウトカムは、1年後の体重減少と2年後の体重維持。

 結果として、1年後にロルカセリン群55.4%とプラセボ群45.1%が評価対象として残り、1年後の5%以上の体重減少はロルカセリン群47.5%とプラセボ群20.3%であった。1年間でのロルカセリン群の平均体重減少量は5.8kg、プラセボ群は2.2kg。

 1年目にロルカセリンで5%あるいはそれ以上体重減少を示した患者で、2年目もロルカセリン投与を受けた患者では67.9%が体重減少を維持し、プラセボ投与を受けた患者では50.3%が体重減少を維持。 有害事象は、頭痛、めまい、吐き気が頻度が高かった。重篤な有害事象の発生頻度は両投与群においてほぼ同等。

気づき)

・1年後の中断率が50%と高いのは、なぜ?

・製薬会社のスポンサーのついた研究のため、利益相反あり?

・セロトニン作動薬による体重減少の評価は不十分なので、慎重な市販後評価が必要か

N Engl J Med. 2010 Jul 15;363(3):245-56.

Multicenter, placebo-controlled trial of lorcaserin for weight management.

BACKGROUND: Lorcaserin is a selective serotonin 2C receptor agonist that could be useful in reducing body weight.

METHODS: In this double-blind clinical trial, we randomly assigned 3182 obese or overweight adults (mean body-mass index [the weight in kilograms divided by the square of the height in meters] of 36.2) to receive lorcaserin at a dose of 10 mg, or placebo, twice daily for 52 weeks. All patients also underwent diet and exercise counseling. At week 52, patients in the placebo group continued to receive placebo but patients in the lorcaserin group were randomly reassigned to receive either placebo or lorcaserin. Primary outcomes were weight loss at 1 year and maintenance of weight loss at 2 years. Serial echocardiography was used to identify patients in whom valvulopathy (as defined by the Food and Drug Administration) developed.

RESULTS: At 1 year, 55.4% of patients (883 of 1595) receiving lorcaserin and 45.1% of patients (716 of 1587) receiving placebo remained in the trial; 1553 patients continued into year 2. At 1 year, 47.5% of patients in the lorcaserin group and 20.3% in the placebo group had lost 5% or more of their body weight (P<0.001), corresponding to an average loss of 5.8+/-0.2 kg with lorcaserin and 2.2+/-0.1 kg with placebo during year 1 (P<0.001). Among the patients who received lorcaserin during year 1 and who had lost 5% or more of their baseline weight at 1 year, the loss was maintained in more patients who continued to receive lorcaserin during year 2 (67.9%) than in patients who received placebo during year 2 (50.3%, P<0.001). Among 2472 patients evaluated at 1 year and 1127 evaluated at 2 years, the rate of cardiac valvulopathy was not increased with the use of lorcaserin. Among the most frequent adverse events reported with lorcaserin were headache, dizziness, and nausea. The rates of serious adverse events in the two groups were similar.

CONCLUSIONS: In conjunction with behavioral modification, lorcaserin was associated with significant weight loss and improved maintenance of weight loss, as compared with placebo.

これから)日病薬関東ブロックのプレ発表、職員面接1名、理科大早期実習3名、weekly review、感染委員会、管理会議。明日は走ろう!

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カテゴリー: EBM

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