Statin Use on the Rise

January 6th, 2015 No comments »

CDC reports statin usage for the control of cholesterol has increased  by one-third over the past decade. In 2012, 28% of people over age 40 reported using a cholesterol-lowering medication, up from 2003 rate of 20%. Most of the increase was in statins. 71% of adults with cardiovascular disease and 54% of adults with high cholesterol reported medication usage to control their cholesterol, according to an article in the Washington Post by Tanya Lewis.

The high use of statins has several implications for persons with obesity. Obviously, this trend improves the health of many persons with obesity and  are at greater risk of cardiovascular disease. However, it can also be a confounding factor in research studies. Looking for changes in cardiovascular disease through weight loss (by any method) can be more difficult to find because of the effectiveness of statins. High use of statins was referenced as one of the reasons by the Look Ahead trial was terminated early.

 

Antidepressant Study Roils FDA, Media

June 20th, 2014 No comments »

A new study on the use of antidepressants and suicides is roiling the Food and Drug Administration and the media. The study by Lu et al and published in the BMJ this week investigated whether widely publicized warnings in 2003-4 from the FDA about possible increased risk of suicide risks with antidepressant use in children and adolescents were associated with changes in antidepressant use, suicide attempts and completed suicides among young people. Researchers studied 1.1 million adolescents, 1.4 million young adults and 5 million adults.

Researchers found that the background studies behind the FDA warnings showed mixed outcomes. Nevertheless, after the FDA warnings, trends in antidepressant use and poisonings changed abruptly after the warnings. The FDA warnings received widespread and repeated media coverage becoming “frightening alarms to clinicians, parents, and young people.”

The decline was greatest among young adults, less among young adults and adults. Simultaneously, there were significant increases in psychotropic drug poisonings in adolescents and young adults but not among adults. Completed suicides did not change for any group. The study also found that there was no increase in alternative therapy usage

The researchers concluded that, “Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce possible unintended consequences of FDA warnings and media reporting.”

The media reaction to this study has been to shout that the warnings backfired and led to more suicide attempts. Meanwhile, the FDA is saying it sees no reason to change the warnings.

Why bring this study up in an obesity report? Several reasons.

First, obesity and depression co-occur in many people. There is so much overlap that most clinical trials of obesity interventions routinely exclude persons with depression from the study population. One reason is adherence. But another significant reason is that many antidepressants cause weight gain. In a recent study in JAMA Psychiatry found that people taking citalopram (Celexa) gained more than 2.5 pounds a year, on average. Those taking fluoxetine (Prozac) gained 1.5 pounds and those on sertraline (Zoloft) gained nearly 2 pounds in the course of a year. On the other hand, those taking bupropion (Wellbutrin) lost an average of nearly .5 pounds a year. (Bupropion is one component of the drug, Contrave, together with naltrexone, currently under consideration by the FDA for the treatment of obesity.) The discontinued drug, Meridia, was originally developed for the treatment of depression when its potential for weight loss was identified.

The main FDA warnings came out in 2003-2004.However in May, 2007, the FDA expanded the warnings to include young adults. The next month a FDA advisory panel recommended against approval of the drug rimonabant for the treatment of obesity, in part because of concerns of increase suicidial ideations. (See Stephanie Saul’s article in the New York Times.) Approval of rimonabant was reversed in 2008by the European Medicines Agency after the FDA’s negative decision.

Second, it seems evident now that the evidence base for the FDA warns was at best mixed. But the media so amplified the warnings that the crescendo did not admit of any doubt or consideration that maybe adolescents and young adults actually needed these medications and did not have any good alternatives. Unintended consequences are real but our current system, for all its reliance on scientific analysis, provides little room for doubt and discussion. The media like clean, crisp ‘talking points’ that fit their pre-defined “frames”, e.g. pharmaceutical companies are bad, natural remedies are good, etc. Changing the media’s approach is very difficult; there are just too many outlets. The FDA, on the other hand, is a single organization that can incorporate this experience into future activities.

 

Anti-Obesity Drugs Advance

December 20th, 2013 No comments »

Novo Nordisk has filed a New Drug Application with the Food and Drug Admistration for a 3 mg dose of liraglutide, a once-daily human GLP-1 analogue, as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight  in adults with obesity, or who are overweight with comorbidities. The emerging evidence indicates that GLP-1 reduce hunger-driven feeding, the hedonic value of food and food-motivation. Further, there is some evidence that the effect of GLP-1 on reward behavior is not limited to food-related reward but also extends to cocaine, amphetamine and alcohol reward. See review. In a clinical trial, at 2 years patients on liraglutide lost 3 kg more weight than those on orlistat. The two year prevalence of  prediabetes was reduced by 52% and the metabolic syndrome by 59% with improvements in blood pressure an lipids.

Also, Orexigen Therapeutics Inc. has resubmitted it New Drug Application to the FDA for its anti-obesity compound, Contrave. In November, Orexigen submitted results from a study requested by the FDA to rule out major adverse cardiovascular events.  The company has expressed confidence that Contrave with will be approved by the FDA next year in the US and in Europe as well.

 

Aetna to Reimburse Obesity Drugs

November 28th, 2012 No comments »

Aetna, the nation’s third largest health insurer, has announced that it will provide reimbursement coverage for Vivus Inc’s obesity treatment, Qsymia, and Arena Pharmaceutical’s Belviq, which will go on the market next year.

No details are available yet on the duration of coverage or any requirements to show weight loss. Nevertheless, this is a major breakthrough in the resistance of the insurance industry to cover drugs to treat obesity.

 

New obesity drug now available

September 18th, 2012 No comments »

VIVUS Inc. has announced today the availability of Qsymia for the treatment of obesity. (The drug was previously called (Qnexa) Approved by the Food and Drug Administration, studies indicated patients with obesity had an average 10% weight loss when used in conjunction with a lifestyle modification program.

According to the VIVUS press release:

The safety and efficacy of Qsymia were evaluated in two multicenter, phase 3 trials that included more than 3,700 patients:  severely obese patients (the EQUIP study) and overweight or obese patients with at least two weight-related comorbidities, such as hypertension, hypertriglyceridemia, type 2 diabetes or central adiposity (the CONQUER study). The average weight loss in EQUIP was 10.9% on Qsymia 15 mg/92 mg and 1.6% for placebo (ITT-LOCF, p<0.0001). The average weight loss in CONQUER was 9.8% on Qsymia 15 mg/92 mg, 7.8% on Qsymia 7.5 mg/46 mg and 1.2% for placebo (ITT-LOCF, p<0.0001).

The most common adverse reactions for patients treated with Qsymia included tingling sensation of hands and feet, dizziness, altered taste, insomnia, constipation and dry mouth.

The Qsymia REMS program is intended to inform prescribers and female patients of reproductive potential about the following: an increased risk of orofacial clefts in infants exposed to Qsymia during the first trimester of pregnancy; the importance of pregnancy prevention for females of reproductive potential receiving Qsymia; and the need to discontinue Qsymia immediately if pregnancy occurs.

For more information about Qsymia, go to www.Qsymia.com.

For full prescribing information go to http://vivus.com/docs/QsymiaPI.pdf.

 

FDA Urged to Broaden Scope in Reviewing Obesity Drugs

August 16th, 2012 No comments »

The George Washington University School of Public Health and Health Services has issued a report on “Obesity Drug Measures, A Consensus Report of Considerations Regarding Pharmacologic Intervention.” The report, chaired by Christine Ferguson of the STOP Obesity Alliance, identifies three categories of interested populations: the obese and ‘well’, the obese with risk factors and the obese and sick. It recommends, inter alia, that criteria for obesity drugs should characterize individuals at different levels of health, feeling and functioning. Likewise, it recommended limited access to those individuals for whom the benefits outweighed the risks. The report also recommends an FDA-approved instrument to measure the impact of weight on quality of life as well as moving beyond the cardiometabolic-centered criteria in current use. The report recommends evaluation of other effects of obesity, such as joint pain, urinary incontinence and functional limitations, such as decreased mobility. Uniquely, the report broached the issue of drugs for use in the pediatric population, a topic not previously discussed and much in need of debate. The report is available at: http://sphhs.gwu.edu/releases/obesitydrugmeasures.pdf

 

FDA Approves Qnexa

July 18th, 2012 2 comments »

Vivus Inc. announced today that the Food and Drug Administration (FDA) has approved its anti-obesity drug, Qnexa, which has been renamed Qsymiatm .  Qsymiatm is a combination drug, composed of phentermine and topiramate, both of which have been approved by the FDA for years. As we have previously reported, Osymiatm has the most impressive weight loss of any obesity drug. The FDA has recommended patients discontinue the drug if they lose less than 3% of body weight on the mid-dose formulation or less than 5% on the high dose after 12 weeks. They also recommended monitoring of heart rate for people on the drug and that women of child-bearing age have a negative pregnancy test every month while using the drug. A Risk Evaluation and Mitigation System (REMS) plan includes distribution through certified pharmacies, a medication guide and a timetable for assessments.

The Risk Evaluation and Management Strategy information, Medication Guide, Safety Information and Health Provider Training Program can be accessed at: http://www.qsymiarems.com/

 

 

NYT Coverage of FDA Lorcaserin Decision

June 28th, 2012 No comments »

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.