Effect of bremelanotide on body weight of obese women: Data from two phase 1 randomized controlled trials

作者：Carl Spana, Robert Jordan, Steven Fischkoff · 发表于：Diabetes Obesity and Metabolism · 年份：2022 · DOI：10.1111/dom.14672 · 被引用次数：15 · 研究领域：Regulation of Appetite and Obesity、Biochemical Analysis and Sensing Techniques、Pharmacology and Obesity Treatment

AIMS: The melanocortin 4 receptor (MC4R) plays a central role in appetite regulation, and agonistic activity at this receptor promotes satiety. Results from two randomized controlled clinical trials examine the effects of bremelanotide's agonism at MC4R on caloric intake and body weight. METHODS: were studied in two phase 1, single-centre, randomized, double-blind, placebo-controlled trials. Study A matched subjects 1:1 to receive subcutaneous placebo or bremelanotide three times daily for days 1-15. Study B was a crossover trial with six distinct treatment sequences consisting of three 4-day treatment periods, investigating once-a-day and twice-a-day exposure to bremelanotide versus placebo. Subjects received one of the three treatments twice-daily during each period: 0 mg/0 mg, 2.5 mg/0 mg or 2.5 mg/2.0 mg bremelanotide. Body weight and food intake were recorded in detail daily. Adverse events were recorded throughout both studies. RESULTS: In Study A, 27 of 30 bremelanotide subjects (90.0%) completed the trial and exhibited a significantly greater reduction in body weight after 16 days versus placebo [least squares mean difference (95% CI), -1.3 (-1.9 to -0.8) kg; p < .0001]. Mean caloric intake in bremelanotide subjects was decreased versus placebo, with a magnitude of reduction of approximately 400 kcal/day throughout Study A (p < .01). In Study B, 15 of 27 subjects (55.6%) completed all three phases. Significantly greater reduction of mean body weight occurred in twice-...