Archive for June, 2012

NYT Coverage of FDA Lorcaserin Decision

June 28th, 2012

Here is the New York Time’s coverage of the FDA’s historic decision on lorcaserin by Andrew Pollack.

Prescription Drug to Aid Weight Loss Wins F.D.A. Backing

By 

The first new prescription diet pill in 13 years won approval from the Food and Drug Administration on Wednesday, providing a new option for the roughly one-third of American adults considered obese.

Now the question is whether people will use it. Despite a seemingly huge market, diet drugs have not sold well in the past, in part because people tend to use them for only a short time.

The new drug, developed by Arena Pharmaceuticals of San Diego, has been known as lorcaserin and will be sold under the name Belviq by Eisai Inc., the American branch of the Japanese pharmaceutical company.

Before Belviq’s approval, only one anti-obesity medicine had been approved for long-term use — Roche’s Xenical, which reached the market in 1999 and is rarely used because of modest weight loss and unpleasant effects on the digestive system.

The history of diet pills has been marked by many safety problems and product withdrawals, which has made the F.D.A. reluctant to approve new drugs. Belviq itself was turned down by the agency in 2010, but Arena came back with new data that assuaged the agency’s safety concerns.

Some patient advocates and doctors who treat obesity say there is a need for new medicines to help to plug a “treatment gap” between diet and exercise, which do not work for many people, and the more radical option of bariatric surgery. They say obesity itself is a serious disease that causes other health problems like diabetes and heart disease.

In announcing the approval of Belviq, the F.D.A. suggested that it ascribed to that point of view. “Obesity threatens the overall well being of patients and is a major public health concern,” Dr. Janet Woodcock, director of the drug evaluation center at the F.D.A., said in a statement.

Belviq is the first drug to reach the market for Arena, which was founded in 1997. Its stock price has more than quadrupled in the last two months, with much of the gain coming after an advisory committee to the F.D.A. recommended approval of Belviq by a vote of 18 to 4 on May 10. On Wednesday, the stock rose 29 percent to $11.39.

Arena said it was not clear yet when the drug would be available to patients and what it would cost. Because the F.D.A. deemed that there was some potential for the drug to be abused, the Drug Enforcement Administration must now decide what controls to place on prescribers, a process that Arena said could take four to six months.

Belviq provides only modest weight loss. In the two main clinical trials, those who took the drug lost an average of 5.8 percent of their weight after a year, while those using a placebo lost 2.5 percent. However, some 23 percent of the patients using Belviq lost at least 10 percent of their body weight.

Taken twice a day, Belviq activates a receptor in the brain, called serotonin 2C, in a way that controls eating and makes people feel full.

The main safety concern is that Belviq works somewhat like fenfluramine, a drug that was part of the popular fen-phen combination but was withdrawn from the market in 1997 because it damaged heart valves. The F.D.A. said Wednesday that it was satisfied that Belviq was unlikely to cause such problems.

The agency is not requiring patients taking Belviq to be monitored for valve damage. However, it recommends that people stop taking the drug if they do not lose 5 percent of their weight in 12 weeks, because they are not likely to benefit and should not be exposed to the risks. (About 40 percent of patients taking the drug in clinical trials achieved that much weight loss in 12 weeks.)

Arena committed to conducting six studies after the drug reached the market, including one to determine whether the drug increased the risk of heart attacks and strokes.

Some advocates hailed the approval. “The F.D.A. seemed so scared of another fen-phen recall that they had like a psychological hurdle to approve any new drug,” said Morgan Downey, editor of the online Downey Obesity Report. “I think they maybe now have gotten beyond that.”

The F.D.A. could approve a second obesity drug, Vivus’s Qnexa, next month.

But Public Citizen, the consumer group, called the approval a “reckless” action and predicted Belviq would eventually have to be taken off the market for safety reasons.

The next hurdle for Arena and Eisai will be selling the drug. This would seem easy given the tens of millions of obese and overweight people. Some analysts are projecting annual Belviq sales will exceed $1 billion.

But no other obesity drug has done that well. Only a small percentage of obese people use such drugs now.

While that is partly because there are few good choices, another issue is that insurers have been reluctant to pay for such drugs. Medicare Part D, which pays for drugs for seniors, explicitly excludes obesity drugs, along with drugs for erectile dysfunction and hair growth. Only 10 state Medicaid programs clearly pay for weight-loss drugs, according to a 2010 study by researchers from George Washington University.

Another issue is that patients tend to stop using the drug, in part because they are dissatisfied with the weight loss. The 5.8 percent average weight loss in the clinical trials of Belviq means that a person weighing 220 pounds, the average weight at the start of the trial, would still weigh 207 pounds a year later.

Even in the clinical trials, in which people tend to take drugs more faithfully than in real life, more than 40 percent of patients stopped taking Belviq before the year was out.

Dr. Ed J. Hendricks, an obesity specialist in Sacramento, said that he and other doctors might try prescribing Belviq in combination with phentermine, to essentially reconstitute the once popular fen-phen combination. “Once that word gets out that it works the same way, you are going to have a huge demand,” said Dr. Hendricks, who was on the advisory committee that voted in favor of approving Belviq.

Perhaps to discourage this, the label of Belviq states that the drug has not been tested for use with other weight-loss agents.

Christine Ferguson, a professor of public health at George Washington University, said one concern had long been that obesity drugs would be used by people who were not obese. “One of the challenges will be to ensure that it’s responsibly used,” she said.

 

 

FDA Approves Lorcaserin

June 27th, 2012

The Food and Drug Administration announced today that it has approvedlorcaserin (to be marketed as Belviq)for the treatment of adult obesity. The drug was developed by Arena Parmaceuticals and went through two advisory committee panels. The final panel voted to recommend approval by a vote of 18-4. This is the first drug for treating obesity approved by obesity since sibutramine was approved in 1997.

Lorcaserin is a novel drug that targets a specific serotonin receptor. It was a different serotonin receptor which was implicated in heart valve problems associated with use of the dexfenfluramine component of Fen-Phen. The FDA briefing document for the Advisory Committee meeting on May 10, 2012 states  that it “is unlikely at the proposed clinical dose” will activate the receptor implicated in the heart valve problem.

The receptor lorcaserin does impact is concentrated in the central nervous system (CNS) and regulates feeding behavior.

In the latest published study of the drug, the BLOOM-DM study led by Patrick O’Neil, 604 patients who were obese or overweight with type 2 diabetes were randomized into a treatment group and a placebo group. Both groups received lifestyle counseling. The group on drug lost 4.5-5% of their initial body weight while the placebo group lost 1.5%. PubMed: Clinical Trial of Lorcaserin in Type 2 diabetes Weight loss in patients with type 2 diabetes is notoriously difficult to achieve.  A 5% weight loss is considered to provide clinically meaningful changes. Weight reduction was evident at 2 weeks which means that patients who don’t see weight loss are likely to discontinue use early on in treatment. Glycemic control improved more in the lorcaserin group. There were not significant changes between the group on drug and on placebo in regard to cholesterol, triglycerides and blood pressure. The lack of statistical significance may be due to the use by a majority of patients being on blood pressure or lipid medications at the start of the trial.

Arena Pharmaceuticals, developer of lorcaserin, has agreed to conduct a number of post-approval trials, including one to assess cardiovascular effects.

 

Updated AHRQ Recommendations

June 25th, 2012

The US Preventive Services Task Force has issued new recommendations for clinical diagnosis and treatment of adult obesity. 12 to 26 sessions in the first year can help people manage their weight.” While obesity and encouraging healthy lifestyle choices are related health issues, Dr. Grossman emphasized that the Task Force issued two separate recommendations. He explained, “The Task Force’s obesity screening recommendation focuses on offering or referring obese patients to comprehensive weight management programs. This recommendation is intended to improve all health outcomes, and not only risks for cardiovascular disease. The healthy lifestyles recommendation focuses only on counseling to encourage healthy lifestyle choices to prevent cardiovascular disease.”

In a separate recommendation, the Task Force determined that for people who have low risk for heart disease, counseling to encourage healthy lifestyle choices, such as a healthful diet and physical activity, offers only small benefits in reducing the risk for cardiovascular disease.

The Task Force also stated that this counseling may be beneficial to some people, depending on their individual risk factors, including known cardiovascular disease, high blood pressure, and high cholesterol.

See the Clinical Statement AHRQ_USPSTF_ Adult obesity

And the Evidence Support: http://www.uspreventiveservicestaskforce.org/uspstf11/obeseadult/obeseart.htm

In a separate paper, the USPSTF did not recommend counseling for cardiovascular disease, finding weak evidence for behavioral counseling for diet and physical activity in primary care. Annals: USPSTF recommendation on counseling for cvd

 

 

Texas Grapples with Costs of Bariatric Surgery

June 24th, 2012

The New York Times reports on the issue of Texas, which has one of the highest rates of obesity in the country, grappling with the costs of bariatric surgery in Medicare and Medicaid. NYT:Spending for Weigh Loss Surgery Increases in Texas

No doubt this scenario will be played out in many states in the coming years. I’ve always said, “Obesity is too expensive to treat and it is too expensive not to treat.” This article bears this out. The tipping point for me is that at least with treating, we are reducing suffering for some humans. Predictably, at the end of the article a professor is cited as saying that the state could reach many more people with less expensive lifestyle interventions and improve their health enough to save far more dollars than bariatric surgeries do. This would be true if any lifestyle intervention was shown to achieve bariatric surgery’s long term, significant weight loss, with a reduction in co-morbidities, such as type 2 diabetes. But the professor’s statement is still, after millions of dollars of research on lifestyle changes, only a hypothesis, yet to be established.

 

The Global Obesity Picture

June 24th, 2012

So here is the global obesity picture. The World Health Organization slides for age standardized  BMI a women and men over 20. WHO estimates that 1 billion people are obese worldwide, increasing to 1.5 billion by 2015. It is no longer a problem in the developed world but is increasing in low and middle income countries. Only some areas which have no reporting, or have geographical or political conflicts appear not to be seeing an increase in obesity.

For men

For women

 

This graph is data from the OECD (Organization for Economic Cooperation and Development ) and depicts the obesity picture in the developed world. The different bars report data from 1990 to 2009, all are increasing. It is a little hard to see but all of the countries which have measured data have higher rates than self-reported data. South Korea and Japan on the far left are probably inaccurate as obesity in their societies should probably be calculated from a BMI of 25 or 27, not a BMI of 30.

Is obesity leveling off? Possibly yes in children  in Australia, China, England, France, Netherlands,New Zealand, Sweden Switzerland and USA, Olds T, et al, Evidence that the prevalence of childhood overweight in plateauing: data from nine countries Int J Pediatr Obes 2011 Oct;6(5) (5-6):342-60.  PubMed: Evidence prevalence childhood obesity plateauing

An historical note here. A great many analyses assume that our obesity problem began in the post-war period or at least from the 1970s. That is not quite correct. As this poorly copied graph shows, the increase in BMI can be traced back to the 1870s. This is from The Changing Body by a number of economists, including one Nobel Prize winner, Robert Fogel, Roderick Floud, Bernard Harris and Sok Chul Hong.

Another paper for the National Bureau of Economic Research shows a similar timeline.

What are the projections?

The OECD projections for the selected developed nations to 2020.

The point is: all lines rise to the right: increased levels of adiposity throughout the population.

Is obesity leveling off? Possibly yes in children  in Australia, China, England, France, Netherlands,New Zealand, Sweden Switzerland and USA, Olds T, et al, Evidence that the prevalence of childhood overweight in plateauing: data from nine countries Int J Pediatr Obes 2011 Oct;6(5) (5-6):342-60.  PubMed: Evidence prevalence childhood obesity plateauing.

Finucane et al found that between 1980 and 2008, mean BMI worldwide increased by 0·4 kg/m(2) per decade for men and 0·5 kg/m(2) per decade for women. National BMI change for women ranged from non-significant decreases in 19 countries to increases of more than 2·0 kg/m(2) per decade  in nine countries in Oceania. Male BMI increased in all but eight countries, by more than 2 kg/m(2) per decade in Nauru and Cook Islands. Male and female BMIs in 2008 were highest in some Oceania countries, reaching 33·9 kg/m(2) (32·8-35·0) for men and 35·0 kg/m(2) (33·6-36·3) for women in Nauru. Female BMI was lowest in Bangladesh (20·5 kg/m(2), 19·8-21·3) and male BMI in Democratic Republic of the Congo 19·9 kg/m(2) (18·2-21·5), with BMI less than 21·5 kg/m(2) for both sexes in a few countries in sub-Saharan Africa, and east, south, and southeast Asia. The USA had the highest BMI of high-income countries. In 2008, an estimated 1·46 billion adults (1·41-1·51 billion) worldwide had BMI of 25 kg/m(2) or greater, of these 205 million men (193-217 million) and 297 million women (280-315 million) were obese. Lancet: Finucane_global_bmi increases


 

Comments Sought on Gestational Diabetes

June 16th, 2012

The Agency for Healthcare Research and Quality (AHRQ) has a draft document available for comment on screening and assessment of gestational diabetes. Gestational diabetes has been implicated as a factor in childhood obesity and is a serious health concern for the mother. Please take the time to review and comment. AHRQ: Draft Comments Gestational Diabetes

 

Is Obesity Jumping Species?

June 11th, 2012

The Sunday Review of the New York Times had a fascinating piece “Our Animal Natures” by Barbara Natterson-Horowitz and Kathryn Bowers. They have an upcoming book, “What Animals Can Teach Us About Health and the Science of Healing.” They discuss how animals have many of the same diseases as humans, including cancer, addiction and cutting or self-harm. They do discuss the increase in body weight among animals. They note that animals in the wild often have cycles of gaining and losing weight. But when there is an abundance of food and access to it, weight gain will follow. This applies not only to household pets but to wild animals as well. They state, “Remarkably, it is the landscape around an animal that determines whether its weight stays steady or rises.” They speculate that it may be a interruption in circadian rhythms caused by light pollution which has brightened our planet. Or, gut microbes. NYT: Our Animal Natures

One thing their excerpt did not address was whether the increase in human obesity was also seen in animal obesity.  YC Klimentidis et al did address this in an article published in the Proceedings,Biological Science of the Royal Society last June. They examined samples consisting of over 20,000 animals from 24 populations (12 divided separately into males and females) representing 8 species living with or around human populations in industrialized societies. In all populations, the trend of body weight over time was increasing.      They calculate the probability of all trends being in the same direction by chance is 1.2 x 10-7 . They found the average mid-life body weights have risen among primates and rodents living in research colonies as among feral rodents and domestic dogs and cats. The authors conclude, “The consistency of these findings among animals living in varying environments, suggests the intriguing possibility that the aetiology of increasing body weight may involve several as-of-yet unidentified and/or poorly understood factors (e.g. viral pathogens, epigenetic factors). PubMed: Canaries in the coal mine: a cross-species analysis of the plurality of obesity epidemics

This phenomenon has implications beyond the obesity epidemic. Researchers at the National Institutes of Health have observed that many standard control rats and mice used in biomedical research are sedentary, obese, glucose intolerant and on a trajectory to premature death. This, they state, may confound data interpretation and outcomes of human studies. Fundamental aspects of cellular physiology, vulnerability to oxidative stress, inflammation and associated diseases are affected by changes in dietary intake and expenditure. PubMed: “Control” laboratory rodents ‘metabolically dead’

 

Doubts about food deserts don’t deter head of HHS

June 10th, 2012

The June 10th Washington Post has an insightful article on the federally-funded food desert initiative in Philadelphia. The article describes how an hypothesis (lack of access to healthy foods leads to eating unhealthy foods which leads to obesity) becomes a large experiment before research is done to determine if it is going to work. WaPo: Will Philadepphia’s experiment in eradicating food deserts

Last month, at the Weight of the Nation conference, Department of Health and Human Services Secretary Kathleen Sebelius took the hypothesis one step further elevating food deserts into a cause of obesity. She said, “Obesity can be caused by any combination of factors.  For some it’s an addiction like smoking.  For others it’s a lack of fresh fruits or vegetables near their home. “ This is pretty sloppy work for a conference so highly organized by the CDC and HHS. An addiction? Still being researched I believe. People are looking at whether certain foods may be “addictive” not whether excess adipose tissue itself is addictive. When a national health leader elevates putative causes like addiction and food deserts to actual causes, a disservice is done and real progress is delayed.