By Robert Finn  |  Thu, 29 Jul 2010 22:30 GMT
Elsevier Global Medical NewsBreaking NewsTwo different doses of naltrexone in combination with bupropion resulted in significantly more weight loss than did a placebo in a 56-week trial involving 1,742 overweight and obese participants. According to the study, published online in the journal the Lancet on July 30, patients taking 32 mg of naltrexone together with 360 mg sustained release bupropion daily lost on average 6.1% of their body weight (6.1 kg or 13.4 pounds), significantly more than patients taking placebo, who lost 1.3% of their body weight (1.4 kg or 3.1 pounds). Patients taking a lower dose of naltrexone – 16 mg daily – along with 360 mg bupropion lost 5.0% of their body weight (4.9 kg or 10.8 pounds). This too was significantly greater than placebo, according to Dr. Frank L. Greenway of Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, and colleagues (Lancet 2010 July 30 [doi:10.1016/S0140-6736(10)60888-4]). Investigators conducted the study at 34 sites in the United States. The study population included men and women aged 18-65 years with a body mass index of 30-45 kg/m2 and uncomplicated obesity or a BMI of 27-45 kg/m2 with dyslipidemia or hypertension. Eighty-five percent of the participants were women, and 75% were white. Their weight averaged 99.5 kg (219.4 pounds). In addition to the study drugs or placebo, participants were instructed to follow a mild diet (500 kcal/day deficit) and were told to increase their physical activity. Among patients who completed the trial, 62% on the higher dose medication and 55% on the lower dose medication lost at least 5% of their body weight, compared with just 23% of the patients taking placebo. Thirty-four percent of the completers on the higher-dose medication and 30% of those on the lower-dose medication lost at least 10% of their body weight, compared with 11% of those on placebo. Patients on the combination treatment also experienced significant improvements in waist circumference, insulin resistance, HDL cholesterol, triglycerides, and high sensitivity C-reactive protein, compared with patients on placebo. However, while mean blood pressure decreased slightly from baseline in the placebo group, it was unchanged in either of the naltrexone-bupropion groups. Only 50% of the participants completed all 56 weeks of the trial, with similar discontinuation rates in all three groups. While a total of 26 patients experienced serious adverse events, none of those was related to study treatments, according to the investigators. Several adverse effects were significantly more frequent in the treatment groups than in the placebo group. These included nausea, headache, constipation, dizziness, vomiting, and dry mouth. No psychiatric adverse event, including insomnia, anxiety, and depression, was more common in the treatment groups than in the placebo group. Compared with the placebo group, patients in the treatment groups reported experiencing significantly less hunger, and significantly less difficulty in controlling their eating. The naltrexone-bupropion combination is thought to affect two key systems in weight control. Bupropion affects the hypothalamic melanocortin system, which is thought to control feelings of hunger, while naltrexone affects the mesolimbic reward system. The study was funded by Orexigen Therapeutics, which manufactures the naltrexone-bupropion combination under the trade name Contrave. Dr. Greenway has received consulting fees and travel support from Orexigen; is a member of advisory boards for Orexigen, Baronova, Biologene, Catalyst Pharmaceutical Partners, GlaxoSmithKline, Jenny Craig, Leptos Biomedical, Novo Nordisk, Obecure, Schering-Plough Research Institute, NuMe, and Origin Biomed; is a consultant for Basic Research, Dow Chemical, General Nutrition, Lithera, Otsuka Pharmaceutical Development and Commercialization, and Third Rock Ventures; and has received research grants or has grants pending from Amylin, Lilly, Orexigen, Merck, Sanofi-Aventis, Arena Pfizer, Bristol-Myers Squibb, Nastech, Schering Plough, GlaxoSmithKline, and Hollis-Eden. He also holds three patents related to obesity treatment. Several of the other co-authors acknowledged membership on Orexigen’s advisory board, receiving consulting fees as well as research grant support from Orexigen. Three other co-authors acknowledged being current or former employees of Orexigen and owning stock in the company. Subject Codes: top_stories; diabetes; general_primary; endocrinology; http://www.imng.com July 29, 2010   06:30 PM EDT