A Resident's Review

OZEMPIC

If you’ve been on social media lately, you’ve likely heard about this “miraculous new” medication. Ozempic has recently been touted as the latest solution for those looking to shed some extra inches around the waist. I’ve personally received countless inquiries from patients, family members, and friends about whether it’s legitimate and if they should consider trying it. After all, who wouldn’t be interested in something that could potentially help burn off those stubborn ten pounds? Especially with so many people reporting great results. But what does this medication actually do? Is it safe and effective for everyone? And if so, does that mean everyone should be taking it? I’ll share some information on the medication, the data, the known risks, and my thoughts on the matter.

BACKGROUND

Despite the recent popularity surrounding this medication, it is not a new drug. Ozempic is actually the brand name for the active chemical ingredient “semaglutide.” Semaglutide was first discovered in 2012 and was officially approved for use by the FDA in 2017 for the treatment of Type 2 Diabetes under the brand name Ozempic. It has remained a great choice for Type 2 Diabetes, demonstrating consistently improved outcomes for those who take the medication regularly. One of these improved outcomes is weight loss. After further studies of its effects on weight loss, semaglutide was again FDA approved in 2021 under the brand name Wegovy for chronic weight management. This is a major reason for its recent recognition and popularity among those struggling with their weight.

So, what exactly is semaglutide and how does it work? Semaglutide belongs to a class of medications called “glucagon-like peptide-1 receptor agonists,” or GLP-1 for short. It works by mimicking the natural GLP-1 hormone in the body to stimulate insulin production in response to meals. This mechanism is great for managing blood sugar levels, but it doesn’t fully explain how semaglutide has been so effective for weight loss. More recent studies have revealed that semaglutide affects much more than we originally thought, and current studies are still continuing to investigate all the various ways semaglutide does what it does. What we do know for sure is that semaglutide causes weight loss through several mechanisms. It suppresses appetite, delays the emptying of the stomach, promotes increased fat metabolism, and modulates a number of different hormones that regulate sugar production and breakdown within the body.

THE DATA

The most influential study that led to semaglutide’s FDA approval for weight loss specifically was the STEP (Semaglutide Treatment Effect in People with Obesity) program, with the STEP 1 trial being the most pivotal. This study included 1,961 individuals who were followed over a period of 68 weeks while taking weekly semaglutide injections. Participants who took semaglutide lost an impressive average of 14.9% of their body weight. Not only did participants lose weight, but they also demonstrated improvements in other areas of cardiovascular health, including blood pressure and cholesterol levels. The STEP program included a total of eight trials incorporating various populations and settings, which repeatedly demonstrated the efficacy of semaglutide. Further studies are continuously being published demonstrating its benefits on multiple different facets of health, stretching from heart health, to brain health, and more.

This makes a lot of intuitive sense to me. If weight loss, in general, is beneficial for someone’s overall health, then it logically follows that weight loss resulting from a medication would show similar benefits.

It’s important to mention here that the STEP trials also demonstrated that individuals who stopped taking semaglutide regained their lost weight. This is a key element of treatment and a common phenomenon with many other weight loss treatments. It would be fantastic if one could take semaglutide for a year, shed a bunch of pounds, and then stop taking the medication while maintaining the weight loss. Unfortunately, studies have consistently shown that the same mechanisms used to achieve weight loss are reversed after stopping the medication. This leads to increased hunger, decreased satiety, and a slowed metabolism. This is an important aspect to emphasize because it highlights the role of other forms of weight management in addition to semaglutide. Clinical trials have also shown increased weight loss in individuals who take semaglutide AND participate in diet or exercise programs.

Semaglutide needs to be thought of as an open-ended, long-term treatment with the goal of supplementing with diet and exercise. Diet and exercise alongside semaglutide treatment are important not only to achieve further weight loss but also to maintain the weight loss if a patient ever wishes to stop or can no longer access the medication. I think understanding this expectation and mindset is crucial for anyone considering taking semaglutide. Entering treatment with the expectation that weight loss will be permanent without engaging in other lifestyle changes could result in dissatisfaction and poor outcomes in the long run.

THE RISKS

Wow, well I’ve probably just made semaglutide sound like the best thing since the invention of the wheel. Practically guaranteed weight loss along with other health benefits? Sign me up! If you have a cautious mind, you may be having similar questions as I did when I first heard of these results. What’s the catch? While semaglutide seems to hold a lot of promise for many people, there have also been risks identified with its use.

The major risk identified thus far comes from studies involving rodents. Semaglutide, especially at higher doses and for longer treatment courses, increased the risk of developing thyroid C-cell tumors, including medullary thyroid cancer. This adverse effect seems to be exceedingly rare, and more research is needed to fully understand how common this occurrence may be in human populations. The current recommendation is to avoid semaglutide use in individuals with a history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), a condition that predisposes individuals to the development of thyroid cancer. In fact, the medication is required to carry a black box warning detailing these risks. Additionally, early studies indicated an increased risk of pancreatitis in patients on the medication, although recent evidence is beginning to dispute this claim. However for now, I would still avoid taking the medication if you have a personal history of pancreatitis. The silver lining here is that the risk of pancreatitis seems to be low, and thyroid cancer has only been conclusively observed in rodents.

Common Side Effects

Aside from these major risks, semaglutide has been associated with a wide range of negative side effects due to its impacts on the digestive system. Among these side effects, nausea, diarrhea, vomiting, constipation, and abdominal pain are the most common. Studies have cited that anywhere from 20-44% of individuals taking semaglutide experience nausea, making it the most common side effect. While these side effects may be common, they tend to be relatively mild for most people compared to the benefit of weight loss. However, on the severe end of the spectrum, patients may suffer from cholelithiasis (gallbladder stones), severe constipation lasting days to weeks, or severe vomiting and/or diarrhea causing dangerous dehydration. Although these severe symptoms are much less common, they are important to keep an eye out for.

Recommendations for Specific Populations

With all this in mind, I generally advise avoiding semaglutide use in patients who already struggle with abdominal issues such as constipation, diarrhea, abdominal pain, nausea, or irritable bowel syndrome (IBS), as semaglutide may worsen these conditions significantly. Additionally, patients who have recently undergone abdominal surgery, especially bariatric surgery for weight loss, should not take a medication that affects how their digestive system processes food. Lastly, those actively suffering from psychiatric eating disorders (e.g., anorexia nervosa, bulimia, binge-eating disorder) should not take this medication due to the risk of worsening their condition and a lack of data of the risks in this population.

Anyone considering taking semaglutide should do so in partnership with a medical provider to determine an appropriate dose and monitor for any severe side effects.

THE REALITY

Semaglutide’s effect on weight loss is a massive discovery. We see documentation of weight loss methods across human history dating all the way back to 1500 BCE. Ancient Egyptians of the time believed weight was related to a balance of fluids in the body and would utilize a strict regimen of laxatives, emetics, and dietary restrictions to achieve weight loss. Since then, our ideas and treatments around weight loss have evolved tremendously. Herbal remedies, natural supplements, meditations, religious practices, exercise programs, special diets, medications, and surgical procedures have all been developed around this universal issue. Now here we are in the 21st century, with a medication that shows consistent and reliable weight loss outcomes.

Before I share more of my conclusive viewpoint on the matter, I want to clarify my thoughts on obesity as a whole. Our societal culture surrounding obesity weight loss have long been toxic and highly stigmatized. Obesity has traditionally been viewed as an issue of willpower and laziness rather than a true medical condition. We have since come a long way in terms of media representation, policy awareness, and being health-focused, but we still have a long way to go. It is critical to acknowledge that everyone’s life is unique and filled with varying complex social and medical factors that may contribute to someone’s overall weight. While one individual may be struggling financially to afford healthier food options, another person may lack transportation to a nearby gym. Another may have a highly demanding sedentary job and lack the necessary time it takes to lose weight. These are just a few small examples out of the many ways societal factors can influence our health outside of our control. It is important for patients and providers alike to recognize these influences contributing to this national issue. We need to shift our mindset from viewing obesity as a reflection on the individual to recognizing it as a larger societal issue and a medical diagnosis. I empathize with my patients who struggle with their weight and I know this is an incredibly challenging task to tackle.

With that being said, obesity is still a very real health threat. We live in a society where 1 in 3 adults classify as being overweight, and more than 2 in 5 adults classify as being obese. More individuals in America die today from complications related to obesity than from starvation, and 1 in 10 Americans suffer from diabetes. I strongly believe that in an ideal world, semaglutide should be a cheap and affordable option for every overweight individual. Aside from the special populations I mentioned earlier, semaglutide represents a reliable and relatively safe way to lose weight.

Unfortunately, semaglutide is currently very expensive and unaffordable for most people. Our current medical system is an expensive one, and semaglutide can cost anywhere from $600 to $1,300 per month for uninsured individuals. Insurance companies are not jumping at the chance to pay for such a pricey medication for the masses either. Currently, insurance companies approve Ozempic for the treatment of diabetes after submitting prior authorization. I have yet to see coverage strictly for weight loss in those who do not have diabetes.

Semaglutide seems to be a revolutionary treatment for obesity and overweightness. Many more people could potentially benefit from it than those who are currently prescribed the medication. However, it does come with risks, and it’s crucial that no one takes this medication without being monitored by their medical provider. Looking ahead, I am hopeful future research will continue to highlight the benefits and uncover the risks associated with semaglutide, and that solutions will be found to make this treatment more affordable and accessible to a broader range of people.

So, maybe we all should be taking Ozempic?

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