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Title: Weight Loss in Patients Taking Sibutramine Is Greater With Specific Genetic Make-Up
URL: http://www.pslgroup.com/dg/22DF8A.htm
Doctor's Guide
October 1, 2008

BETHESDA, Md -- October 1, 2008 -- Obese patients with a specific genetic make-up lose more weight when taking sibutramine and undergoing behavioural therapy compared with those without this genetic make-up, reports a study in Gastroenterology.

"We found significantly lower values for weight, BMI [body mass index], and proportion of body fat in patients taking sibutramine. The candidate gene variations provided useful markers of enhanced response to the drug," said lead author Michael Camilleri, MD, Mayo Clinic, Rochester, Minnesota.

"Gene variations may help select obese patients who are more likely to experience improved outcome with this treatment. Since the different markers were present in almost 50% of patients, inclusion of screening for these genetic markers before prescribing the medication may even be cost-effective from a public health perspective."

Weight loss with sibutramine is highly variable. Therefore, researchers assessed the influence of specific markers of candidate genes controlling serotonergic and adrenergic mechanisms (alpha-2A receptor, 5-HTTLPR and GNbeta3) on weight loss/body composition in response to sibutramine or placebo.

In the randomised, double-blind, pharmacogenetic study, Dr. Camilleri and colleagues evaluated behavioural therapy and sibutramine 10 or 15 mg daily or placebo for 12 weeks in 181 overweight or obese participants. They measured body weight, BMI, body composition, gastric emptying, and genetic variation.

Study results showed that sibutramine at both doses, given in combination with behavioural therapy, caused significant weight loss (P = .009). The drug resulted in lower values for weight (P < .01), BMI (P < .001), and proportion of body fat (P = .05) compared with placebo. Weight loss at 4 weeks was a predictor of weight loss achieved at 12 weeks.

There was a statistically significant gene-by-dose interaction for GNbeta3 genotype. For each candidate gene, treatment effects were observed at 12 weeks (P < .017) for all specific genotype variants. The research showed gene pairs resulted in greater sibutramine treatment effects on weight.

However, there was no evidence of synergism between combinations of 2 genotypes on the response to sibutramine therapy compared to the effect on weight loss associated with individual genotypes.

"Our results suggest the genetic make-up of patients could predispose their responsiveness to a drug. This could have important implications for the future of personalized molecular-based or individualised medicine," said Dr. Camilleri.

SOURCE: American Gastroenterological Association

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