The prospects for any new obesity drugs’ becoming available in the near future dimmed considerably after the majority of the Food and Drug Administration’s Endocrinologic Drugs Advisory Panel recommended against approval of the phentermine-topiramate (Qnexa) combination and the serotonergic drug lorcaserin (Lorqess) at meetings last summer and fall. Then in February, the FDA put its decision on another drug combination – the antidepressant bupropion and the opioid antagonist naltrexone (Contrave) – on hold when it requested a large cardiovascular safety trial in overweight and obese people before the agency would consider approval.
Dr. Rodbard, who is past president of the American Association of Clinical Endocrinologists and the American College of Endocrinology, said that although these drugs had potential side effects, she considers their side effects to be lower than the risk of remaining obese, adding that "it is a tragedy that we do not have more and better drugs available for treatment of obesity, and that there has not been a larger and more effective and sustained program to change the lifestyle habits of Americans with regard to diet and exercise."
Although Dr. Youdim acknowledged that concerns over the safety of the drugs are legitimate, "there is a lot of bias around drugs for obesity, because the thought is that if patients would just stop eating, they’d lose weight. ... The rigor placed on these drugs is a lot greater because of that bias." But obesity is a disease, she added, "and there should be treatment options available to us," just as there are options available for other diseases.
Although weight-loss drugs have not been effective on their own, they have been useful adjuncts to lifestyle modification, and "the cornerstone of treatment in a select group of patients who are having trouble adhering to lifestyle recommendations."
Dr. Youdim said that certain drugs are associated with some weight loss and can be used – not "completely without indication" – to help patients lose weight. For example, a patient who is both overweight and clinically depressed could be prescribed bupropion, someone with insulin resistance can benefit from metformin, and a patient with type 2 diabetes who requires insulin may benefit from exenatide (Byetta). All three of these drugs are associated with weight loss.
Dr. Rodbard said that in patients with diabetes in whom exenatide is indicated, about a third of those receiving it "have very dramatic weight loss ... especially in some patients with a very massive degree of obesity to begin with," and that this loss is "very nicely sustained." Published data support the notion that the combination of the glucagonlike peptide–1 receptor agonists with insulin will help to reduce the weight gain associated with insulin therapy, she added.
Metformin has a very small effect on weight, but appears to have beneficial effects on the risk of heart disease and cancer; "hence, it is one of the backbones of therapy for type 2 diabetes and used in combination with nearly all other medications," she added.
As for the FDA-approved weight-loss drugs, Dr. Rodbard said that she rarely uses phentermine, and – when it was available – she rarely used sibutramine, which was used mainly because there were not many other options available. The side effects of orlistat, she said, are unacceptable "to all but a very few patients."
Dr. Louis Aronne, director of the comprehensive weight control program at New York–Presbyterian Hospital, said that there clearly is a need for more medical treatments for obesity – as well as improved access to comprehensive weight-loss programs that are affordable and effective – before the clinicians opt for surgery. "Right now, a patient can go from Weight Watchers to the operating room" for bariatric surgery because of the gap in treatment and dearth of medical options, he said.
Dr. Aronne is a developer of an online program designed to address the treatment gap and poor access to comprehensive weight-loss programs. The "BMIQ" program is a 16-session, online, comprehensive program run by a dietician in a group setting. It includes dietary and exercise counseling that is aimed at helping obese people with type 2 diabetes to lose weight and manage their diabetes by using a "weight-centric approach" efficiently and without extra costs. Primary care physicians refer their patients to the program; after the patient fills out an evaluation form, the physician receives information on the patient along with recommendations on how to manage that patient. For example, the clinician is alerted if the patient is taking over-the-counter sleep medications that contain strong antihistamines, which can both cause weight gain and make it difficult to lose weight; eliminating them is "like giving someone an appetite suppressant," he said.