FDA Declines Approval for Contrave as Latest Weight Loss Therapy Drug

Despite a recommendation by the Endocrine and Metabolic Drugs Advisory Committee in December, the US Food and Drug Administration has denied approval for Orexigen Therapeutics and Takeda Pharmaceutical Co’s weight loss drug Contrave (naltrexone/bupropion). The agency is requesting another clinical trial due to concerns about the cardiovascular safety profile.

FDA Requests Further Studies on Cardiovascular Safety

Specifically, the FDA requested that a study be conducted “of sufficient size and duration” to demonstrate that the drug does not increase the risk of heart attack or stroke.
Contrave combines an antidepressant – bupropion, brand name Wellbutrin – and a drug used for addiction called naltrexone. In clinical studies, 35% of patients who took Contrave lost at least 5% of their body weight, a level that measures successful weight loss.
The major complications found in patients on Contrave were increased blood pressure and heart rate. Two patients were also noted to have seizures during the studies and the FDA is reviewing a case of fatal heart attack.
Orexigen has argued that the ingredients that comprise Contrave have been on the market for 20 years and have not shown any major cardiovascular-safety problems. The company had already agreed to a large post-approval study to test the risk of stroke and heart attack and proposed that limitations be set to exclude patients with high cardiovascular risk from being placed on Contrave for weight loss.
Had it been approved, Contrave would be the first new diet pill in a decade. Two other weight loss therapy drugs were rejected last year, including Lorquess (lorcaserin hydrochloride) and Qnexa (phentermine/topiramate). A previously approved diet drug, Meridia, was removed from the market last year due to cardiovascular safety concerns.

Yale Targets Weight Loss Pill

Researchers from Yale University may be close to finding a weight loss pill that boosts energy, and reduces the risk of type 2 diabetes. The scientist found that lowering a key enzyme in the brain, prolylcarboxypeptidase (PRCP), can decrease appetite and improve energy, resulting in weight loss.
The study, published in the Journal of Clinical Investigation was performed on mice. The researchers found that PRCP controls another essential hormone that regulates energy expenditure and inhibits food intake. The result of targeting PRCP was weight loss and decreased risk of type 2 diabetes.
Senior author Sabrina Diano, associate professor in the Departments of Obstetrics, Gynecology and Reproductive Sciences, and Neurobiology says, "Our research provides the first evidence that breaking down molecules in the brain that regulate metabolism is an important component of weight control.”
The molecule, alpha-melanocyte stimulating hormone (alpha-MSH) remained higher when PRCP was blocked, providing a new target for weight loss pills.
The study was conducted on mice that were naturally lean and then on mice that had PRCP removed. They ate less and lost weight. The mice had lower alpha-MSH, a hormone produced in the hypothalamus.
The mice were even able to lose weight when given a “fast food” type diet, containing forty five percent fat. Blocking PRCP in the brain resulted in less weight gain compared to mice given a regular diet. The findings could result in new and improved weight loss pills to treat escalating rates of obesity and type 2 diabetes. The study is considered a major advance in weight loss and obesity research.

Low-Calorie Sweeteners Can Help with Weight Loss

Some recent reports have questioned the weight loss and caloric control benefits of low-calorie sweeteners. A new study, however, supports the idea that low-calorie sweeteners can significantly reduce a person’s caloric intake and the tendency to overeat and thus help with weight loss.
Despite ongoing concerns and debates about any harm artificial and other low-calorie sweeteners such as aspartame and stevia may cause, millions of people turn to these products as table sweeteners and to the low-calorie and/or low-sugar foods that have them as ingredients as a way to control caloric intake and their weight.
Some concerns about low-calorie sweeteners are that individuals who use them may compensate for the lower caloric intake by eating more of other foods, and that they may feel less satisfied after consuming sugar substitutes and feel hungry, which could lead them to overeat.
In a new study, published in the journal Appetite, researchers gave study participants (both healthy and overweight adults) a pre-meal that contained either sucrose (table sugar), aspartame, or stevia (a low-calorie herbal sweetener). Participants who received the aspartame or stevia consumed significantly fewer calories overall, did not overeat, and did not say they had increased feelings of hunger.
The results of this study support the findings of a 2009 meta-analysis in which investigators evaluated 224 studies. In that report, published in the American Journal of Clinical Nutrition, the researchers concluded that while there were concerns that including non-nutritive sweeteners in the diet promoted an increase in caloric intake and contributed to obesity, “most of the purported mechanisms by which this occurs are not supported by the available evidence.”
Beth Hubrich, a dietitian with the Calorie Control Council, noted that when low-calorie sweeteners are “used as part of an overall healthy diet,” both as a table sweetener and in low-calorie products, they “can be beneficial tools in helping people control caloric intake and weight.”

Majority of Americans Fail to Maintain Weight Loss

Findings from Penn State College of Medicine researchers show that only one in six obese or overweight Americans are able to maintain weight loss. The scientists say the findings are important. Targeting individuals who are successful at keeping weight off could help others.
The researchers say the only way to reduce the number of obese American is by making weight loss programs available to more people and more effective. They note that obesity rates in America doubled between 1980 and 2004.
Jennifer Kraschnewski, M.D., M.P.H., assistant professor of medicine and public health sciences says, "It is important for health professionals to understand the true prevalence of long-term weight loss, as it may help to change the underlying beliefs and influence clinical practice. Studies have shown that physicians may not believe offering weight loss advice and counseling is a worthwhile activity in clinical practice. An awareness of our findings may encourage health professionals to pursue weight loss counseling for overweight patients."
The study sample included an analysis of 14,306 people from the National Health and Nutrition Examination Survey, from 1999 to 2006. The findings showed that after a year, thirty six percent of individuals maintained five percent weight loss.
Other findings revealed that women were more likely than men to keep off ten percent of weight. Sixteen percent of diabetics, compared to non diabetics were able to maintain weight loss. Partnered or married individuals had a lower prevalence of long-term weight loss success.
If researchers could identify those who have success with maintaining weight loss, Kraschnewski says the impact on public health would be significant, even though reducing five percent of body weight seems modest. “Particularly, those individuals who have lost at least five percent and kept it off -- one in three Americans who have ever been overweight -- may represent a unique opportunity to reach a target population who has had some success but could benefit from greater weight loss efforts."
Sixty nine percent of those studied said weight loss of at least 10 pounds the previous year was intentional. Long-term weight loss was most successful among younger people, females, non-Hispanic whites and those with higher education and better overall health. The findings show Americans can lose weight – the problem is finding ways to keep it off.