The phase 3b IGNITE study shows that naltrexone/bupropion (Contrave/Mysimba, Orexigen) combined with a comprehensive lifestyle intervention led to greater weight loss at 26 weeks than usual care consisting of a doctor's advice to lose weight and be more active.
Specifically, obese and overweight patients who responded to naltrexone/bupropion plus a comprehensive lifestyle intervention lost 9.5% of their body weight, whereas patients in the usual-care group lost just 0.9% of their body weight at 26 weeks (P < .001), the primary study end point.
Moreover, "the efficacy was maintained for at least 78 weeks, a longer duration than has been previously studied," Amy Halseth, PhD, with Orexigen Therapeutics, La Jolla, California, and colleagues report in an article published online in Obesity.
The results provide hope for meaningful weight loss, Scott Kahan, MD, MPH, director of the National Center for Weight and Wellness, George Washington University, Washington, DC, and chair of the clinical committee of the Obesity Society, who was not involved in the study, told Medscape Medical News.
"There's an overriding sense of futility among physicians and patients that nothing works for weight management, especially longer-term weight management, and this is a great example refuting that," he said.
Patients in the usual-care group received "what usually happens: the doctor basically tells the patient 'you should lose weight' without providing comprehensive counseling, referrals, or medications."
In contrast, the other study arm showed that "with just a little bit of decent counseling and when appropriate, a medication, we can go a long way; a lot of people lost > 15% of their body weight, which is what you get with lap-band surgery, and [among responders] virtually everyone (80% or more) had a meaningful > 5% weight loss," Dr Kahan added.
"I think this study should incite optimism among clinicians that there's a lot we can be doing if we spend some time with our patients focusing on this," he continued.
"Real-World" Study
As previously reported, another study, the LIGHT trial — to test cardiovascular-disease rates with naltrexone/bupropion — was controversially stopped in May 2015 due to leaked results from 25% of planned enrollment, and the phase 4 CONVENE trial, set to replace the LIGHT study, was also ended, in April 2016, after Takeda sold its US rights to Contrave to Orexigen.
Dr Kahan said it would be good to see a completed cardiovascular-outcomes trial, but as bupropion and naltrexone "have been around for 60, 70 years…I'm not bothered at all" that these trials were not completed, he commented.
Since Contrave includes the antidepressant bupropion, as with all antidepressants, there is a warning that it may cause suicidal thoughts in people under age 24.
The current IGNITE study aimed to assess what may occur in real-world clinical practice.
To be eligible for the trial, patients had to be 18 to 60 years old, obese (body mass index [BMI] 30–45 kg/m2) or overweight (BMI 27–45 kg/m2), with dyslipidemia and/or controlled hypertension — but no diabetes, recent myocardial infarction, severe angina, stroke, seizures, cranial trauma, bulimia or anorexia nervosa, chronic use of opioids, mania, psychosis, acute depression, suicide risk, or regular smoking.
As well as receiving Contrave — starting at a daily dose of 8 mg of naltrexone/90mg of buproprion and titrated up — the 153 patients in the treatment arm received 11 structured phone calls in the first 26 weeks and up to 12 phone calls later on from a coach/dietician, plus online information, individualized goal setting, and tracking tools.
The 89 patients in the usual-care arm received advice to exercise and to try to eat 500 fewer calories a day, given at baseline and at 10 weeks, and tools such as a nutrition tracker, a pedometer, and nutrition information.
At the primary study end point (26 weeks), five of the 89 patients in the usual-care arm were lost to follow-up and two patients discontinued the study. The remaining 82 patients were switched to the treatment intervention (Contrave plus structured care); of these, 35 patients completed 52 weeks and 28 patients completed 78 weeks of the study.
At 26 weeks, 82 of 153 patients in the treatment arm discontinued the study because they had adverse events (35 patients), achieved less than a 5% weight loss (deemed nonresponders so had to discontinue study medication) and/or had elevated blood pressure at week 16 (32), or were lost to follow-up (nine) or for other reasons (six).
Of the remaining 71 patients who continued the study, 61 patients completed 52 weeks and 55 completed 78 weeks.
Significantly more "responders" to the study drug lost at least 5%, 10%, or 15% of their initial weight at 26 weeks compared with patients who received usual care, and this weight loss was sustained for the year-and-a-half study.
Weight Loss at 26 Weeks, Usual-Care vs Treatment Groups
| Weight loss | Usual care (n=82), % patients | Treatment arm* (n=71), % patients |
| > 5% | 12.2 | 84.5 |
| > 10% | 3.7 | 42.3 |
| > 15% | 0 | 12.7 |
The most common adverse events among patients receiving Contrave that led to discontinuation were nausea (7%), anxiety (2.1%), headache (1.7%), dizziness (1.2%), and insomnia (1.2%), which tended to occur in the first month of treatment.
"These results strengthen the body of evidence suggesting combination therapy of naltrexone/bupropion along with lifestyle to promote weight loss is a promising approach to lowering the prevalence of obesity," say Dr Halseth and colleagues
"The results of this study reflect what may be expected to occur in real-world clinical practice," they conclude.
The study was funded by Orexigen Therapeutics. Dr Halseth and three coauthors are Orexigen Therapeutics employees and shareholders; the fourth coauthor was an Orexigen employee and remains a shareholder; and the fifth coauthor is a consultant to the company. Dr Kahan is a consultant for Orexigen, Novo Nordisk, Takeda, Vivus, and Eisai and an unpaid member of the board of directors of the American Board of Obesity Medicine and the Obesity Action Coalition, and he receives textbook royalties from Johns Hopkins University Press and Lippincott Williams & Wilkins.
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Obesity. Published online December 27, 2017. Abstract
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Cite this: Contrave Plus Intense Lifestyle Tops Usual Care for 18 Months - Medscape - Jan 17, 2017.
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