Treatment of Obesity: The Upsides and Downsides

People are always asking me what I think about these new weight-loss medications [for example, Ozempic and Wegovy, trade names for the generic medication semaglutide, in a class of medication called glucagon-like peptide receptor analogs (GLP-1) agonists]. These medications continue to make news headlines and are popping off the (often virtual) shelves like wildfire.

My answer: For people who have trouble with extra weight, have health problems from it, and who are willing to take the medication long-term, the benefits (from what we know so far) on the whole appear to outweigh the risks.

Who will benefit?

For some, these medications, and others in the GLP-1 agonist class and outside of that class (with different mechanisms, discussed below), are lifesavers. When used in combination with comprehensive lifestyle change (including diet, exercise, and behavioral therapy) plus community support, weight-loss-promoting medications can increase physical health and well-being, at least in the short run.

However, medications for obesity (defined simply as having a body mass index greater than or equal to 30), are not a panacea, they don’t work for everyone, and they don’t work forever. Prior to initiation, all patients should be screened for comorbid eating disorders—if binge eating disorder or bulimia is present, eating-disorder-focused treatment, either with an evidence-based group or individual therapy or medication treatment, might be warranted first. Also, especially in the case of the GLP1 agonists, these medications are relatively new, and we don’t yet fully understand the effects of long-term use.

What about people without obesity who want to take weight-loss-promoting medication for cosmetic reasons? To my knowledge, none of these medications have been rigorously studied in these persons; I’d say, they aren’t really safe to take for these reasons, because we don’t know the risk-benefit ratios. We also don't know the long-term consequences of use. Generally, I don’t recommend any medications for people who don’t have a mental or physical health condition to target, all medications have potential downsides. Plus, prescribing weight loss medications for cosmetic reasons raises some ethical concerns, for me. But that’s another topic for another post.

I am definitely an advocate for using medications for obesity treatment when there are good reasons and for the right people.

What medications are out there?

There are a variety of medication options for the pharmacotherapeutic management of obesity. These include pancreatic lipase inhibitors (orlistat), MC4R agonists (setmelanotide), phentermine-topiramate, naltrexone-bupropion, and topiramate among others. Most of these medications have affect appetite directly, altering brain systems that regulate food intake, such as the hedonic and homeostatic systems. The weight-loss benefits are generally modest, and in some cases, side effects are not pleasant, but the individual responses are also quite variable. For some people—and we often don’t know for whom before trying the medication for a while—weight loss can be significant and side effect burdens low.

Most of the side effects from weight-loss-promoting medications are not permanent: stopping the medication usually resolves the issue. That said, caution should be taken when considering topiramate-phentermine, in particular, as it contains a stimulant that can have cardiovascular effects and or be addictive, and requires special training to prescribe. Discussing all the potential side effects for each of these medications is outside the scope of this blog post, but detailed information on this can be obtained by accessing other sources.

GLP-1 agonists (liraglutide, semaglutide) are newer to the scene, seem to promote more weight loss on the whole than the other aforementioned medications, and seem to have a relatively low side-effect burden (the most common side effects are not serious and include injection site irritation and gastrointestinal effects). GLP-1 agonists also have other observed health benefits, including reduction of blood glucose and blood pressure, resolution of non-alcoholic steatohepatitis (“fatty liver”), prevention of major cardiovascular events, improvement of fertility and sex hormone levels, and improvement of obstructive sleep apnea symptoms and cognitive scores, some of which are independent of the weight loss. Tirzepatide, a medication that is used to treat diabetes, which also has some GLP-1 agonist effects, was also recently approved for the treatment of obesity.

Some of these medications (topiramate, naltrexone, bupropion, GLP1 agonists) seem to work, at least in part, through the brain’s reward network and may promote recovery from addictions, too, by reducing craving and or improving self-control. This is especially interesting in the context of the food addiction controversy, which I’ve discussed in other posts.

For many patients with obesity who take weight-loss-promoting medications, weight gain probably often reoccurs after the medication is stopped. In most cases, long-term studies are lacking.

Conclusion

I definitely advocate for the use of these medications, but only for the right patient and for the right reasons. They can be quite helpful, counteracting our body’s very resilient homeostatic systems that stubbornly resist weight loss through many redundant biological mechanisms. Providers should consider treating their patients with obesity with any of these medications if appropriately trained in the use of the medication, and if they feel comfortable assessing the risk-benefit profiles in the context of their patient’s medical and mental health situations.