Weight-Loss Drugs: Risks vs Benefits

Richard M. Plotzker, MD


April 13, 2015

Current Weight-Loss Options

A few months ago, the US Food and Drug Administration approved a high-dose form of liraglutide (Saxenda®) to be used as a weight-loss agent, bringing the number of obesity medications now available to five: orlistat (Xenical®, Alli®), lorcaserin (Belviq®), phentermine/topiramate (Qsymia®), and bupropion/naltrexone (Contrave®). Guidelines suggest that clinicians consider prescribing an obesity drug in patients with a body mass index (BMI) over 30 if they have no other weight-related conditions, and in patients with a BMI as low as 27 if they have comorbidities such as diabetes, hypertension, or dyslipidemia.

Some of these medicines, such as orlistat, have common, annoying side effects such as bowel changes, whereas others, such as liraglutide, have rare but very serious side effects—pancreatitis, in this case. Although this is not likely to occur, it's a doozy when it does.

What does a BMI of 27 look like? I share exam rooms with the bariatric surgeons who come weekly, and they have posted a BMI table on the walls. A person standing 5'6" would have a BMI of 27 at 170 pounds, and a BMI of 30 at 190 pounds—kind of chubby, to be sure, but not necessarily passing the eyeball test for obesity.

If a patient has a BMI of 30 without any health problems but describes a struggle with social stigma or difficulty getting the job he or she wants, I would not consider their motivation to lose weight unreasonable. If the same patient cannot offer any reason for wanting to lose weight, I might be a bit more risk-averse.

A BMI of 27 seems more problematic. In a diabetic population, prescribing liraglutide as a means of losing weight while also lowering glucose has its merits. But would I opt for a weight-loss agent for mild excess weight with hypercholesterolemia or hypertension over a tried-and-true statin or antihypertensive? I would find it hard to make a case for that, given the reality that many of the agents designed for those purposes have been shown to be life-extending.

Then, if the blood pressure and lipids can be controlled with usual medicines, does that raise the bar for introducing weight-loss agents back to a BMI of 30? As the CME article emphasized, the goal of the patient and the goal of the doctor acting in a best professional manner may be different.

Looking back, I wonder whether the heart valve problems associated with dexfenfluramine and the limiting psychiatric symptoms linked to rimonabant might have been considered more acceptable if their use had been limited to more disabling obesity. For now, public demand for the currently approved agents and prescribers' willingness to accept associated risks remain uncertain at best.


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