What role should weight-loss medications play in the treatment of obesity across specialties?

A MedPage Today/Milwaukee Journal Sentinel report last month indicated that weight-loss medications such as Belviq, Qsymia, and Contrave were approved by the FDA based on a minimal weight loss (5% of body weight) but have not been shown to reduce cardiovascular events or other hard endpoints.

We contacted a variety of healthcare professionals by e-mail to ask:

What is the proper role, if any, for medications to promote weight loss?

Is it reasonable to assume that medication-induced weight loss will reduce obesity-related health risks?

Given that these medications seldom produce large and persistent weight losses, how much risk of adverse effects is appropriate?

The participants this week are:

Arti Bhan, MD, head of the division of endocrinology at Henry Ford Hospital in Detroit

Olveen Carrasquillo, MD, MPH, professor, medicine and public health sciences, chief, division of general internal medicine at the University of Miami Miller School of Medicine in Florida

Spyros Mezitis, MD, PhD, clinical endocrinologist, Lenox Hill Hospital in New York City

Carl “Chip” Lavie, MD, FACC, medical director, cardiac rehabilitation, and prevention at the John Ochsner Heart and Vascular Institute in New Orleans (Dr. Lavie discloses he received an honorarium as a consultant and potential speaker for Novo Nordisk, which has a new obesity medication. He is also the author of The Obesity Paradox.)

Gina Moore, PharmD, MBA, assistant dean for clinical and professional affairs, CU Skaggs School of Pharmacy and Pharmaceutical Services, Anschutz Medical Campus at the University of Colorado in Denver

A Multifactorial Approach

Arti Bhan, MD: “Obesity is a complex and multifactorial condition with numerous underlying genetic and environmental contributors. The approach to obesity treatment has to be multifactorial as well. Emerging research has shown that chronic weight gain leads to neurohormonal adaptations in the body, which make weight loss difficult. As physicians, we realize that the vast majority of people need adjunctive measures in order to achieve and sustain weight loss. Medication-induced weight loss is effective in decreasing the risk of obesity-related conditions. Ultimately, it is the amount of weight lost which has an impact on the degree to which complications are reduced; not the means by which the given weight loss is achieved.”

Olveen Carrasquillo, MD: “In general the long-term impact of weight loss medications on body weight is relatively small for most people who take them. Weight loss of at least 5% body weight is one of the most commonly used benchmarks used to determine if the medication has any effect. But the mainstay of any healthy weight-loss program is a combination of appropriate diet and exercise (both aerobic and strength). In my practice that is what I tend to emphasize over medications. ”

Spyros Mezitis, MD: “Obesity is a worsening epidemic in the developed world associated with increased risk for chronic disease including diabetes and cardiovascular disease. Lifestyle changes in the past 40 years including increased caloric intake of fatty foods and lack of exercise due to the dramatic increase of the service sector and the aging population have fueled the obesity pandemic.”

Carl Lavie, MD: “Substantial evidence suggests that those overweight and mildly obese appear to have a better prognosis than do normal weight patients with similar CVD, and the research by my colleagues and me suggests that improving fitness may be more important for these patients than weight loss. On the other hand, most studies show that moderate or Class II obesity and certainly severe or Class III obesity is associated with a poor prognosis, and these patients would likely benefit from weight loss. The prevalence of severe obesity in our society is increasing, and now over 3% of the U.S. population have BMI>40.”

Right Medication, Right Patient

Gina Moore, PharmD: “I think medications are truly a last resort for weight loss and too often consumers are looking for a quick fixrather than addressing the underlying causes of excess weight. Weight-loss medications might be used short term (no more than 3 to 6 months) in individuals who have failed in previous attempts to lose weight for initial motivation, but patients should be closely monitored for weight loss, potential adverse effects, and that they are being compliant with other weight-loss strategies. We know that weight loss reduces obesity-related health risks, but medication-induced weight loss only occurs as long as an individual takes the medicine. The effects of the medicine plateau after a period of time, and unless an individual has undertaken a comprehensive, long-term strategy for weight loss, it is unreasonable to think they’ve done much to improve their long-term health risks. ”

Bhan: “In 1998, the NIH stated that ‘obesity is a chronic disease, and both patients and the practitioner need to understand that successful treatment requires a life-long effort.’ Most interventions leading to weight loss show initial success, with long-term studies showing weight regain. Weight loss medications work as long as they are being used. Given the difficulty patients have in maintaining weight loss, I think that using weight-loss drugs in the right patient is reasonable and will improve their metabolic parameters and quality of life. The ‘right patient,’ for example, is someone with a BMI ≥27 with diabetes, sleep apnea, and symptomatic osteoarthritis.”

Lavie: “It is likely that many patients with more severe obesity would benefit from weight-loss medications that produce 5% to 7% weight loss, and maybe even more so with greater weight loss with bariatric surgery. These therapies may improve quality of life, reduce use of other medications, reduce co-morbidities, and possibly reduce CV events and survival. Proving this will obviously be essential.”

Risks vs. Benefits

Mezitis: “Anti-obesity medications on the market working via increasing metabolism or suppressing appetite may cause at least 5% weight loss that is related to improvement in glycemic and lipemic control and possible decrease in vascular disease. Cardiovascular trial results with these medications are pending and their safety is being monitored. The treating physician must discuss their risks and benefits with each potential patient user, evaluate weight loss and blood test results on an ongoing basis, consider modifying other medications used in conjunction with anti-obesity medications, and register cardiovascular events during treatment.”

Carrasquillo: “Some of these medicines also have unwanted side effects such as gastrointestinal symptoms, which is another reason I seldom use them. In addition, for clinicians who are more evidence-based, we really want to see data that the medications reduce not only body weight but also reduce obesity-related health risks such as diabetes, hypertension, and heart disease. So far, I have not seen much good evidence on those outcomes. That is why I prefer to prioritize diet and exercise. The evidence linking these two lifestyle changes to improved health outcomes is quite clear.”

Moore: “It’s difficult to comment on risk in absolute terms, but in my opinion, bothersome side effects such as loose stools or flatulence that occur with Orlistat are reasonable. Although they aren’t pleasant for the individual taking the medication, you wouldn’t expect to see long-term health consequences. The FDA has been under pressure to approve weight-loss drugs given the obesity epidemic in the U.S., but I think consumers are better served by looking at holistic weight-loss approaches other than relying on medications.”

Lavie: “At present, there is no proven long-term safety of these new obesity medications and also no proven impact on survival or major CV events. Additionally, some of these new medications may increase heart rate, which normally is a marker of adverse autonomic tone. Although the mechanism of the heart rate increases may differ with the various agents, including by direct sinus node stimulation, a new heart failure (HF) medication is being approved because it reduces heart rate by direct sinus node inhibition, which leads to a reduction in HF adverse events. Therefore, higher heart rates with these medications could hurt prognosis in some patients. Some of the weight-loss medications may increase BP and have other potentially serious adverse events, all of which makes demonstrating long-term safety and efficacy, not just for weight loss but for major clinical CV events, more important.”

Bhan: “Weight-loss drugs are not completely without risks. Appropriate patient selection is the key to successful weight loss and decreased risk of side effects. It is imperative that providers prescribing these medications, monitor patients regularly. If weight loss of more than 5% is not achieved in 3 months, a different strategy should be applied. The potential benefit of improving existing comorbidities and preventing additional future problems may outweigh the risk of adverse effects from weight-loss drugs. Long-term follow-up data will give us more information regarding cardiovascular risks and benefits of these medications.”