Genes influence effectiveness of weight-loss drug

October 02, 2008

Obese patients with a specific genetic make-up lose more weight when taking the weight loss drug sibutramine and undergoing behavioral therapy compared to those without this genetic make-up, reports a new study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute.

The obesity epidemic continues to be an increasingly global problem: an estimated 1.6 billion adults worldwide are overweight (body mass index [BMI]>25) and 400 million are obese (BMI>30). In addition, the incidences of diabetes and other debilitating diseases attributable to obesity continue to rise.

While there are numerous options for the treatment of obesity, this study examined sibutramine, a medication approved for the long-term treatment of obesity. The drug creates a feeling of fullness, prevents decline in metabolic rate associated with low calorie diets and causes weight loss, especially when combined with behavioral therapy. However, weight loss with the drug is highly variable. Therefore, a research team at the Mayo Clinic assessed the influence of specific markers of candidate genes controlling serotonergic and adrenergic mechanisms (α2A-receptor, 5-HTTLPR and GNβ3) on weight loss/body composition in response to sibutramine or placebo.

"We found significantly lower values for weight, BMI and proportion of body fat in patients taking sibutramine. The candidate gene variations provided useful markers of enhanced response to the drug," said Michael Camilleri, MD, AGAF, of the Mayo Clinic and lead author of the study. "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 percent of patients, inclusion of screening for these genetic markers before prescribing the medication may even be cost-effective from a public health perspective."

In this randomized, double-blind, pharmacogenetic study, Dr. Camilleri and colleagues evaluated behavioral 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 behavioral therapy, caused significant weight loss (p = 0.009). The drug resulted in lower values for weight, BMI and proportion of body fat compared to placebo (p<0.01, p<0.001 and p=0.05, respectively). Weight loss at four weeks was a predictor of weight loss achieved at 12 weeks.

There was a statistically significant gene-by-dose interaction for GNβ3 genotype. This gene determines the function of G proteins, which are involved in translating the message from surface receptors that bind the transmitters serotonin and norepinephrine (e.g. of cells controlling appetite). Those surface receptors are indirectly influenced by sibutramine, which blocks the reuptake of the two transmitters. For each candidate gene, treatment effects were observed at 12 weeks (p<0.017) for all specific genotype variants. The research showed gene pairs (e.g. for GNβ3and α2A-receptor) resulted in greater sibutramine treatment effects on weight (both p<0.002). However, there was no evidence of synergism between combinations of two 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 individualized medicine," added Dr. Camilleri. As new and exciting research like this study continues into the causes, prevention and treatments for obesity, the role played by the GI tract is becoming more defined. This understanding has the potential to lead to novel endoscopic, pharmacological and nutritional therapies for obesity as well as changes in policies and societal practices related to obesity.

American Gastroenterological Association

SCOUT Trial Reports on the Safety Profile of Sibutramine in Patients with Cardiovascular Diseases (The Physician and Sportsmedicine)
by JTE Multimedia

Abstract: Practice Pearl: These preliminary data from the SCOUT trial appear to demonstrate that sibutramine is well tolerated by high-risk cardiovascular patients. Original Article: Torp-Pedersen C, Caterson I, Coutinho W, et al; SCOUT Investigators. Cardiovascular responses to weight management and sibutramine in high-risk subjects: an analysis from the SCOUT trial.

Anorectic sibutramine detected in a Chinese herbal drug for weight loss [A short communication from: Forensic Science International
by J. Jung (Author), M. Hermanns-Clausen (Author), W. Weinmann (Author)

This digital document is a journal article from Forensic Science International, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser.

Abstract:
In the presented case, a young healthy woman had ordered a Chinese herbal medicine, called ''LiDa Dai Dai Hua Jiao Nang'', via internet. She took this product for approximately 1 week, but on the second day she developed severe headache, vertigo and sensation of numbness. After discontinuing medication, symptoms disappeared within 2 days. For identification of the ingredients, a urine sample as well as a sample of the ''LiDa'' capsule were analysed by GC-MS and HPLC-DAD. One major ingredient was detected...

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Title: Sibutramine effective in real-world patients. (No Drop in Heart Risks).
Publication: Internal Medicine News (Magazine/Journal)
Date: February 15, 2002
Publisher: International Medical News Group
Volume: 35 Issue: 4 Page: 33(1)

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Title: Sibutramine helps weight, lipids in obese adolescents: not yet approved for patients under age 16.(News)
Author: Jane Salodof MacNeil
Publication: Internal Medicine News (Magazine/Journal)
Date: January 15, 2005
Publisher: International Medical News Group
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Title: Sibutramine helped obese teens cut risk factors: the drug allowed 12- to 16-year-olds to lower BMI and improve triglycerides, HDL, and insulin levels.(Obesity)
Author: Jane Salodof MacNeil
Publication: Family Practice News (Magazine/Journal)
Date: January 15, 2005
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Title: Behavioral Tx plus sibutramine sheds pediatric pounds but has CV risks. (Poor Quality of Life).(treatment, cardiovascular)
Author: Michele G. Sullivan
Publication: Clinical Psychiatry News (Magazine/Journal)
Date: May 1, 2003
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Title: Sibutramine effective in major BED domains: binge eating disorder.(Psychopharmacology)
Author: Bruce Jancin
Publication: Clinical Psychiatry News (Magazine/Journal)
Date: August 1, 2003
Publisher: International Medical News Group
Volume: 31 Issue: 8 Page: 31(1)

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Title: Drug therapy advocated in binge eating disorder: topiramate, sibutramine promising.(Psychopharmacology)
Author: Bruce Jancin
Publication: Clinical Psychiatry News (Magazine/Journal)
Date: August 1, 2003
Publisher: International Medical News Group
Volume: 31 Issue: 8 Page: 32(1)

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by Bruce Jancin (Author)

This digital document is an article from Family Practice News, published by International Medical News Group on September 1, 2003. The length of the article is 681 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser.

Citation Details
Title: Sibutramine scores hat trick in eating disorder: bingeing, obesity, depression.(Clinical Rounds)
Author: Bruce Jancin
Publication: Family Practice News (Magazine/Journal)
Date: September 1, 2003
Publisher: International Medical News Group
Volume: 33 Issue: 17 Page: 28(1)

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Sibutramine effective in binge eating disorder; two randomized trials.(Clinical Rounds): An article from: Internal Medicine News
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This digital document is an article from Internal Medicine News, published by International Medical News Group on October 1, 2003. The length of the article is 675 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser.

Citation Details
Title: Sibutramine effective in binge eating disorder; two randomized trials.(Clinical Rounds)
Author: Bruce Jancin
Publication: Internal Medicine News (Magazine/Journal)
Date: October 1, 2003
Publisher: International Medical News Group
Volume: 36 Issue: 19 Page: 24(1)

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