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My thinking on semaglutide has changed—here's an update

Around this time last year, I wrote a blog post on semaglutide, a drug that was initially used to manage type 2 diabetes but has since exploded into fame as a “miracle” weight loss drug. 


Since then, semaglutide, a GLP1 agonist, and the various brand names it’s being marketed under have only gained more attention, leading to shortages across the country. 


So what have we learned in a year of prescribing these drugs? And, has my opinion of them changed?


Semaglutide can mitigate obesity-related complications

We already knew that semaglutide was very effective in helping people lose weight. However, obesity is associated with various complications, including an increased risk of cardiovascular events and heart failure. Two recent studies show that in addition to facilitating weight loss, semaglutide also plays a role in fighting off these effects.


Cardiovascular Risk Reduction

Last year, researchers released a study with over 17,000 people aged 45 or older with a body mass index of 27 or greater. They all had preexisting cardiovascular disease but not diabetes. Half of them received semaglutide and half received a placebo. Compared to the placebo, patients taking semaglutide had a 20% lower chance of cardiovascular event defined as a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. 


This study was widely covered in the news and was accompanied by speculation that it may facilitate insurance coverage of semaglutide. This could make it a much more realistic option for many people who are obese or overweight.


Obesity-Related HFpEF

Semaglutide also has a lot of promise in treating people with something called heart failure with preserved ejection fraction (HFpEF). 


HFpEF is when a patient experiences heart failure despite blood pumping normally, and it is associated with both obesity and diabetes. In a randomized trial (funded by Novo-Nordisk, the maker of Ozempic and Wegovy), with 529 patients with HFpEF and a BMI of 30 or higher, once-weekly semaglutide (2.4 mg) led to reduced symptoms and physical limitations and induced significant weight loss compared to the placebo group. This study was also released last year.


Even though there was a higher incidence of serious adverse events in the semaglutide group, the overall benefits in symptoms, exercise capacity, and weight loss make it a promising option for people with obesity-related HFpEF.


The side effects


Suicidal Thoughts

Although it’s clear that semaglutide works for weight loss and other health issues, there have also been worries about potential side effects, including reports of patients experiencing suicidal thoughts. 


However, a review of the electronic health records of over 240,000 people who were overweight or obese revealed that people on semaglutide had much lower rates of suicidal thoughts when compared to those on non-GLP1R agonists. Looking at a group of over 1.5 million people with type 2 diabetes showed the same results, meaning it is unlikely that it’s the semaglutide that is causing suicidal thoughts.


Anesthesia Risks

Part of what makes semaglutide such an effective weight loss drug is that it causes delayed gastric emptying, meaning when you take it, food stays in your stomach for longer. Although this is great for limiting how much you eat, it can cause problems if you need anesthesia. 


Generally, patients are advised to fast before surgeries to ensure they have an empty stomach while they’re being operated on. However, there have been reports of patients on semaglutide experiencing pulmonary aspiration (food going into the lungs) during surgery, likely due to delayed gastric emptying. 


The American Society of Anesthesiologists suggests stopping semaglutide or other similar drugs one day before surgery if you’re doing daily injections and one week before if you’re doing weekly injections. 


Gastrointestinal Complications

Another study released last year investigated the risks associated with using GLP-1 agonists (semaglutide and liraglutide) for weight loss, compared to bupropion-naltrexone. 


The study analyzed data from 16 million patients and found that GLP-1 agonists were linked to significantly higher risks of pancreatitis (9x), bowel obstruction (4x), and gastroparesis (3x), but not biliary disease compared to a standard treatment protocol. These findings are significant for patients considering these drugs for weight loss, as the risk-benefit balance may differ from their use in diabetes treatment.


Loss of lean body mass

One of the most concerning issues with GLP1 agonists is from where the weight loss is happening. There are strong indications that an outsized portion is coming from ‘lean body mass’ (primarily muscle). This is an area of active research as noted in this article. As the article states: "A literature review also found that the proportion of lean body mass reductions varied between 20% and 50% of total weight lost, which is in line with diet-induced weight loss and bariatric surgery."


If 40% of the weight loss is coming from lean body mass and muscle is critically important for maintaining insulin sensitivity, especially as we age, the risk benefit ratio dramatically shifts for an individual. It is one of the reasons that all of us, especially those taking GLP1 agonists, should maintain regular resistance training starting with body weight exercises like squats, push ups, planks and lunges.


The rebound effect

As well documented is the weight regain once these medications are stopped. On average ⅔ of patients regain their weight and increase their metabolic risk to their baseline within one year of stopping semaglutide according to the Step 1 Trial. This is for patients who had been on the medication for over a year. If this is the case, and it appears to be, then spending on average a thousand dollars a month to end up in the same place a year later seems to be of very low long term value.  


How my opinion of semaglutide has changed

My opinion is still evolving on these drugs. I still don’t consider them to be the first, or even second, or third choice for someone aiming to lose weight and/or mitigate the side effects of being overweight.


That said, there is definitely a space for semaglutide and its related drugs, including in integrative and functional medicine. This is something I’ve become more open to over the last year, as more good studies have been released showing positive results. On balance, it seems like the risks that may be associated with semaglutide are being outweighed by the benefits of losing weight. 


Still, just as with any other pharmaceutical approach to treating chronic conditions, there needs to be clear-cut medical criteria for when to move forward. And, I still believe that lifestyle modifications should be front and center. If successful, they will be equally or more effective and sustainable, but without the lifelong dependence on an expensive prescription drug.


If you are considering semaglutide and would like to discuss your options with an integrative medicine doctor, Dignity Integrative offers a free 15-minute consultation

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