Posts Tagged ‘cardiovascular’

The Obesity Paradox Explained

October 7th, 2011

The “obesity paradox” refers to a phenomenon in which overweight and obese patients with established cardiovascular disease have a better prognosis than normal weight patients. This has been a controversial finding in several studies, indicating to some that weight loss is worse than weight gain. Now, researchers from the Veterans Affairs Palo Alto Health Care System, examined 3,834 male vets. They did find that weight loss was related to higher mortality and weight gain was related to lower mortality, compared to stable weight over 7 years. 

However, 60% of the deaths in the weight loss group were attributable to conditions associated with muscle wasting, including cancer and heart disease. These conditions arose during the seven year period. This study underscores that the obesity paradox may be explained by the distinction between intentional v. unintentional weight loss. As the authors note, clinically supervised intentional weight loss has shown extensive benefits including lowers incidence of cardiovascular events, better overall survival, marked reduction in the metabolic syndrome, inflammatory markers, lipids, prevalence of hypertension and better glucose tolerance. The obesity paradox and weight loss. [Am J Med. 2011] – PubMed – NCBI

 Even very obese adults can improve their cardiometabolic risk factors. Researchers of the Louisiana Obese Subjects Study (LOSS) found most parameters improved with 5% weight loss or more among 390 extremely obese men and women, followed for one year.  The intervention group was under primary medical care, using meal replacements, weight loss medications, especially sibutramine and behavioral counseling. Those in the intervention group lost an average of 13% of their weight while the ususal care group lost an average of 0.9%. 20.7% of participants had substantial weight loss (10%-19.9%) and 15.4% lost over 20%.  There was a “precipitous” decrease in fasting plasma glucose among patients with type 2 diabetes who achieved at least modest weight loss. Systolic and diastolic blood pressure decreased inconsistently. With modest weight loss, patients achieved 22% improvement in triglyceride levels. Only 53% of subjects stayed in the program for evaluation at one year. Incremental weight loss improves cardiometabolic ri… [Am J Med. 2011] – PubMed – NCBI

 A similar result has been observed in severely obese subjects in  the Look AHEAD trial. Effectiveness of Lifestyle Interventions for I… [Diabetes Care. 2011] – PubMed – NCBI

Contrave bites the dust

June 3rd, 2011

After negotiating with the FDA over whether a cardiovascular trial had to be done pre or post approval, the FDA held out and Orexigen folded.  Orexigen Therapeutics, Inc. – Press Release Evidently, the FDA wanted a trial of between 60.00 and 100,000 patients. Orexigen propsed a trial of between 12,000 and 15,000 patients. The FDA said no, of course. Orexigen Says FDA’s Requests for Contrave Trial Aren’t ‘Necessary or Feasible’ – Health Blog – WSJ

 As indicated elsewhere (scroll down to September 10,2010), the FDA is in a bind. An obesity drug of moderate efficacy, they feel, is not worth any risk. While a drug with significant weight loss (read Qnexa) they fear will be used by so many people (since obesity is an epidemic, after all) that unforeseen adverse events will arise and they will have to take the drug off the market. Then there is the head of the FDA Drug Evaluation Center who wants to make drugs for weight loss into drugs for cholesterol or hypertension.( See What’s Up with the FDA, Part 2)  Make no mistake, the FDA bureaucracy is more afraid of the embarrassment of withdrawing a drug from the market (see the Avandia discussions) than they are of the mortality and morbidity of obesity.

Interestingly, (ominiously??) , the Orexigen release indicates that the FDA will hold an advisory committee early next year on the cardiovascular aspects of obesity therapeutics. This could be the final nail in the coffin of obesity therapeutics.