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01-08-2010 | Cardiometabolic | Article

Naltrexone–bupropion combination aids weight loss


Free abstract

MedWire News: Overweight patients taking the combination of extended-release naltrexone and bupropion lose more weight than those taking placebo, shows the randomized COR-I trial.

Both drugs are already used in the management of addiction disorders. They work by suppressing the hypothalamic melanocortin system, while simultaneously stimulating the mesolimbic reward system.

In obese people, the drugs should therefore suppress cravings and help patients to stick to their diet and exercise plans.

The COR (Contrave Obesity Research)-I study, which is reported in The Lancet, enrolled 1742 patients with a body mass index (BMI) of 30-45 kg/m2 and no complications or a BMI of 27-45 kg/m2 plus dyslipidemia or hypertension.

All participants were assigned to a mild hypocaloric diet and exercise as well as to drug or placebo treatment. Half of the patients completed the 56-week study, and 1453 were included in the primary analysis.

Patients given placebo lost 1.3% of their body weight, on average. There were two active-treatment groups, and both lost significantly more weight than did the placebo group.

Specifically, patients taking bupropion 360 mg/day plus naltrexone 16 mg/day lost 5.0% of their body weight, while those taking bupropion plus naltrexone 32 mg/day lost 6.1%.

A weight reduction of at least 5% was noted in 16% of the placebo group, compared with 39% and 48% of the bupropion plus naltrexone 16 and 32 mg/day groups, respectively.

In an accompanying commentary, Arne Astrup (University of Copenhagen, Denmark) warned that strict attention must be paid to the drugs' combined safety profile. There have recently been a number of withdrawals of obesity drugs, which Astrup attributes to "too much focus on efficacy and too little attention on safety."

Based on the drugs' individual safety profiles in other indications, he said that expected side effects for the combination could include insomnia, anxiety, and raised blood pressure "that are difficult to accept for a weight-loss compound."

Greenway et al report that the most frequent side effect was nausea, which occurred in nearly 30% of patients on active treatment, compared with about 5% of the placebo group.

Active treatment was associated with a transient blood pressure increase of about 1.5 mmHg, followed by a decline to slightly below baseline. The biggest fall in blood pressure occurred in the placebo group, however. There were no changes in low-density lipoprotein (LDL) cholesterol levels, but patients on active treatment achieved reductions in triglycerides, C-reactive protein, and increases in high-density lipoprotein (HDL) cholesterol.

But Astrup questioned how relevant these effects are "when the reductions in blood pressure and LDL cholesterol that normally occur with weight loss are absent."

He concluded: "Experience with sibutramine perhaps suggests that more data are needed to get a better overall assessment of cardiovascular risk of this otherwise promising combination therapy for obesity."

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Eleanor McDermid