Genes influence effectiveness of weight-loss drugOctober 02, 2008Obese 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 | |||||||||||||||||||||
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Related Sibutramine Current Events and Sibutramine News Articles New promising obesity drug may have huge potential According to trials, a new obesity drug, Tesofensine, which may be launched on the world market in a few years, can produce weight loss twice that of currently approved obesity drugs. Dieting and medication may reduce blood pressure in patients with hypertension Adults with hypertension may be able to lower their weight and their blood pressure by following a weight-loss diet or using the medication orlistat. Bone mineral content continues to increase in obese adolescents during weight loss Obese teenagers who succeeded in losing weight in a year-long medically supervised weight control program also saw their bone mineral content increase over that period, say researchers from The Children's Hospital of Philadelphia. The finding was reassuring, because adolescence is a critical period for bone health in later life. New clues to how major weight-loss drugs work Some of the most important weight-loss drugs work by enhancing the effect of the brain chemical serotonin. These include sibutramine (trade name Meridia) and fenfluramine, which was recalled after the combination with dexfenfluramine, called fen-phen, was linked to potentially fatal heart valve abnormalities. Medication plus behavior changes helps obese adolescents lose weight The weight loss medication sibutramine, when combined with behavior therapy, allowed hundreds of very obese adolescents to lose an average of 14 pounds over a year. Proposed changes to obesity guidelines may harm children in the US New guidelines on obesity in the U.S. may end up harming children, says an article in this week's BMJ. And an accompanying article goes on to question the financial links between the organisation promoting these proposals and the pharmaceutical industry. New target for obesity and related metabolic disorders A new study reveals an attractive new target for therapies aimed at the treatment of obesity and related metabolic disorders, researchers report in the March Cell Metabolism. OBESITY DRUG COULD SUSTAIN WEIGHT LOSS (p 2119) Results of a clinical trial published in this week's issue of THE LANCET suggest that the drug sibutramine is effective in sustaining weight loss in obese patients. However, questions remain about the drug's long-term safety. Sibutramine is a tertiary amine, originally developed as a potential antidepressant. It has been shown to induce dose-dependent weight loss and to enhance the effects of a low-calorie diet for up to a year. The Sibutramine Trial of Obesity Reduction and Maintenance (STORM) was a randomised trial to assess the usefulness of sibutramine in maintaining substantial weight loss over 2 years. 605 obese patients were recruited from eight European centres for a 6-month period More Sibutramine Current Events and Sibutramine News Articles |
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