A Magic Bullet for Weight Loss?

Stories about the medications Ozempic and Wegovy for weight loss are flooding news outlets and social media lately.  It started with the popularity of these medications with some celebrities and the controversy regarding who had access to the limited supply, but now the conversation has turned to how these medications might revolutionize obesity treatment.  In this month’s buzz, we will break down how these medications work, look at the clinical studies regarding their use, and discuss the controversies they have caused.  

First the basics: Ozempic and Wegovy are the brand names for the drug- semaglutide.  This is a GLP-1 agonist, a type of medication that has been used for years in the treatment of type 2 diabetes.  Ozempic was approved for type 2 diabetes in 2017.  People on the medication often had weight loss and reduced appetite.  In 2021 a study was completed looking at this medication specifically for weight loss.  Shortly after, Wegovy was the first injectable GLP-1 agonist to specifically be approved by the FDA for the treatment of obesity/overweight.  

How does a GLP-1 Agonist work?  These drugs are receptor agonists, meaning they target the same receptors as the compound that they are modeled after- in this case glucagon-like-peptide-1 (GLP-1).  GLP-1 is a hormone secreted in the intestine when we eat, which tells the body to:

•  increase insulin secretion from the pancreas (lowering blood sugar)
• decrease glucagon secretion from the liver (less glucose production)
• slow stomach emptying

GLP-1 also acts as a neurotransmitter in the brain and can increase satiety, or the feeling of fullness, and may decrease cravings.  (Andreasen et al Endocr Connect. 2021 Jul 1; 10(7): R200–R212)

The Evidence:  A study published in The New England Journal of Medicine in 2021 and funded by Novo-Nordisk (the maker of Ozempic and Wegovy), looked at almost 2000 people (most of whom were female and white) who were obese (defined by BMI >30) or overweight (BMI >27) with a weight-related co-morbid condition (like high blood pressure or high cholesterol), but whom did not have diabetes.  In a double-blind design study, they compared those taking a 2.4 mg weekly dose of semaglutide (higher than the Ozempic dose recommended to treat type 2 diabetes) to a placebo group.  Both groups also had lifestyle intervention (diet and exercise counseling every 4 weeks).  

After 68 weeks of the trial, the participants who received semaglutide had a 14.9% average weight loss, compared to 2.4% average loss in the placebo group.  86% of participants had at least 5% weight loss.  Of note, many participants in the placebo group had significant weight loss as well: “31% of participants who received placebo had lost at least 5% of baseline body weight, with 12% and 5% having achieved reductions of at least 10% and at least 15%, respectively”. (Wilding et al N Engl J Med 2021; 384:989-1002). 

Interestingly, a follow up study published in April of 2022 demonstrated that 1 year after stopping semaglutide for weight loss, participants regained on average two-thirds of the weight that they initially lost.  This suggests that for sustained results, remaining on the medication is beneficial. (Wilding et al, Diabetes Obesity and Metabolism, Vol 24, Issue 8, Aug 22, pg 1553-1564)

For more on side effects and other outcomes that the study measured, read the full article here:

https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

The Controversy:  The popularity of these two medications is skyrocketing, in part due to social media, pharmaceutical ads, and celebrity use. There have been shortages of both medications, and for diabetics on Ozempic and other GLP-1 agonists, this has meant that it is becoming difficult to get their treatment for diabetes. The shortages have started to improve recently, but another problem has been that insurance companies aren’t always covering the medications for obesity or weight loss, which leads to a disparity in who can afford to take them.  Many people are circumventing shortages and cost by getting the medications through online companies, some of which have lower levels of provider oversight and support. Some are also getting the medications from compounding pharmacies, which may be using other forms of semaglutide that are not FDA approved for the intended purposes, as noted in recent news articles. (https://www.nbcnews.com/health/health-news/ozempic-wegovy-semaglutide-compounding-weight-loss-safe-rcna72990)

The bottom line: Semaglutide is effective for weight loss with a pretty low side effect profile if prescribed correctly (especially when compared to other weight loss medications).  This could be a game changer for some people who have health risks associated with obesity or overweight and who have been unable to lose weight through other methods.  Sustained weight loss likely means continuing the medication for a prolonged period of time, and if the medication is stopped, significant regaining of weight can occur.  Lifestyle changes should accompany the medication for optimal health benefits and to enable more people to be able to successfully stop the medication with sustained weight loss.  These medications may make lifestyle changes easier for people who have struggled with exercise and a healthy diet. Fat loss doesn’t always occur in the areas that we would like it to- so facial fat loss can lead to the appearance of premature facial aging, or “Ozempic Face” as it has been called.  It is important to know what you are taking- especially if you are getting a compounded version of the medication.

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