Combination Drugs for Weight Loss Work

Two studies presented at the Obesity 2009 meeting have shown positive effects on weight loss using a combination of new agents. 

In the first study, presented by Dr. Steven Smith (Pennington Biomedical Research Center, Baton Rouge, LA), researchers showed that a combination peptide treatment with pramlintide and metreleptin(Amylin Pharmaceuticals), two analogs of amylin and leptin, which are peptides involved in satiety and adiposity signaling, significantly reduced body weight when compared with placebo or compared with therapy with pramlintide or metreleptin alone.

Among patients deemed “evaluable,” a prespecified analysis that included only patients with a minimum of 24 weeks of drug exposure, all five doses of the pramlintide/metreleptin combination –180 µg/2.5 mg, 180 µg/5 mg, 360 µg/1.25 mg, 360 µg/2.5 mg, and 360 µg/5 mg — significantly reduced body weight compared with placebo. On average, weight loss was 7% with the drug combinations and 2% with placebo.

Presenting the results of the 608-patient dose-ranging study during the late-breaking clinical-trials session, Smith noted that patients with a body-mass index <35 kg/m² had significantly more dose-dependent weight loss than more obese individuals, a finding that has been observed in other trials.

Overall, roughly 60% of patients completed the 28-week phase 2 trial, with most patients dropping out because of adverse injection-site reactions. In addition to the injection-site adverse events, the most commonly reported side effect was mild to moderate nausea. No cardiovascular or psychiatric safety signals were observed.

In a second study presented during the late-breaking clinical-trials session, Dr. Caroline Apovian (Boston University School of Medicine, MA) presented data from a phase 3 randomized controlled trial comparing the efficacy and safety of naltrexone and bupropion (Orexigen Therapeutics, La Jolla, CA) with placebo in 1,496 patients [2]. After one year of treatment, those randomized to drug therapy lost 6.4% of their body weight compared with 1.2% in the placebo arm. Nausea was the most commonly reported side effect, and drug treatment was not associated with any cardiovascular or psychiatric side effects, report investigators.

Smith SR, Aronne LJ, Apovian C, et al. Pramlintide/metreleptin combination treatment for obesity: effect of dose and baseline BMI on magnitude of weight loss. Obesity 2009; October 27, 2009; Washington, DC.

Apovian C, Aronne L, Wyatt H, et al. Results of the phase 3, 56-week, COR-II study: Naltrexone SR/Bupropion SR combination therapy led to significant and sustained weight loss in overweight and obese subjects. Obesity 2009; October 27, 2009; Washington, DC.