This blog provides an overview and reviews some of my concerns as a HAES® (Health At Every Size®) Registered Dietitian about GLP-1 receptor agonist medications, the weight loss drugs everyone seems to be taking or talking about.

 First, let me say that this blog post could easily be a book. There are so many things to discuss, but I don't have time to write that, and you likely don't have time to read it.

Glucagon-like peptide-1 receptor agonists, also known as GLP-1s or semaglutide, are a class of drugs that mimic the actions of the hormone GLP-1. GLP-1 hormones are released from the small intestines, stimulating a glucose-dependent insulin release, slowing gastric emptying, and reducing post-intake glucagon (the hormone that stimulates the liver to make glucose) release. It is thought that with type 2 diabetes, there is a reduction in GLP-1 hormone secretion, which results in elevated blood sugars. GLP-1s are quickly broken down after their release by the enzyme dipeptidyl peptidase 4 (DPP-4). The synthetic version of GLP-1 is resistant to DPP-4, so it lasts longer in the body.

 These drugs were initially made for the treatment of diabetes and were approved in 2005 by the FDA. They have multiple actions that support blood sugar regulation. One unique mechanism of these medications is that while they stimulate insulin (which lowers blood sugars), they have a reduced risk of causing hypoglycemia ( too low blood sugars) compared to many other diabetes medications that do have this potentially fatal risk. Eventually, a side effect of weight loss was noticed with the use of GLP-1s, and then the drug companies modified it and received FDA approval for its use in intentional weight loss. Ozempic is the dosing intended for blood sugar management for type 2 diabetes, while Wegovy is the same drug at a higher dosage, intended for weight loss. Both are made by the company Novo Nordisk. I find that people are more familiar with the drug "Ozempic," though this version is intended for diabetes management. However, it is commonly used off-label for intentional weight loss. These medications are weekly self-injections; another version is Rybelsus, a daily oral tablet for type 2 diabetes management. Other GLP-1 receptor agonists include Dulaglutide (AKA Trulicity), Tirepatide (AKA Zepbound and Mounjaro), and Liraglutide (AKA Saxenda).

These drugs, in short, worry me. Here's why:

 ·      Limited long-term research. Yes, semaglutide has been in use since 2005, but at much lower dosages. Currently, the most extended study at the Wegovy dosage is two years. (Side note: Interestingly, we see weight trending upwards at the two-year mark, but this is not addressed in the research.) These medications are intended to be used for the remainder of one's life. We do not have research on what these medications do when taken for more than two years. What is the impact of taking a drug that stimulates insulin release from a normally functioning pancreas? Could this result in overworking the pancreas and perhaps increase the risk of developing diabetes?

 

·      Who is researching GLP-1s? The people who are studying semaglutide drugs are being paid by the drug companies that make them, either as direct employees or via grant support and advisory fees. Talk about a conflict of interest!

 

·      The misleading headlines/reporting on these medications. Here is one example: In the fall of 2023, Novo Nordisk (the company that makes Ozempic and Wegovy) put out a company announcement (before releasing the study) that semaglutide was found to reduce cardiovascular events by 20% when compared to people receiving a placebo. Lo and behold, the actual numbers were much less staggering. Per the study, 6.5% of patients who took semaglutide experienced death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, while 8.5% of the group taking the placebo did. The 20% statistic is the relative risk, whereas the absolute risk reduction is less than 2%. Absolute risk reduction is a much more accurate representation of an individual's risk reduction. Regan Chastain breaks this concept down in her fantastic substack, which I highly recommend following. 

 

·      The side effects: boxed warning. Semaglutide has a boxed warning (the strictest warning) from the FDA about the risk of thyroid C-cell tumors due to animal studies that found that rodents developed thyroid tumors when exposed to GLP-1 agonists. You should not take semaglutide if you or you have a family history of medullary thyroid cancer or multiple endocrine neoplasia type 2.

 

·      The side effects: GI complications. GLP-1s are a gut hormone, so unsurprisingly, many of the side effects impact the gastrointestinal tract. On Wegovy's website, it reads: "The most common side effects include nausea, diarrhea, vomiting, constipation, stomach (abdomen) pain, headache, tiredness (fatigue), upset stomach, dizziness, feeling bloated, belching, gas, stomach flu, heartburn, and runny nose or sore throat." Wegovy's clinical trials report that 44% of people taking the medication experience nausea, 30% diarrhea, and 24% vomiting. Along with more serious side effects occurring in 9.8% of participants in the clinical trials, including gastroparesis, pancreatitis, and acute kidney injury. Ileus, a potentially life-threatening intestinal blockage, was added to Ozempic's warning label in September 2023. There have been increasing cases of gastroparesis (delayed gastric emptying) being reported with semaglutide use, though this is still being investigated. I believe that folks who are taking these drugs for intentional weight loss are unsurprised and unalarmed by the gastrointestinal side effects, as they are likely contributing to the lack of appetite and weight loss. 

 

·      The side effects: Medication absorption issues. These drugs slow gut motility and reduce stomach acid, which can impact the absorption of other medications. Seven medications were tested by Novo Nordisk, claiming to find no drug interactions with semaglutide. However, this has only been tested at the Ozempic dosage; we do not have data for the dosage level of Wegovy. Plus, only 7 medications were tested. We are seeing reports of people becoming pregnant who take oral birth control medication and semaglutide. This is especially scary, as the prescribing information for these drugs states that people should stop taking semaglutide for at least two months before becoming pregnant. This is due to animal studies that have shown that semaglutide can cause fetal growth issues and fetal death.

·      The side effects: mental health/ suicidality. Recent studies are being conducted due to reports of "psychiatric adverse events" with the use of semaglutide medication, including suicidal thoughts. Wegovy now carries a warning about suicidal behavior and ideation. This could be related to the above concern of medication absorption issues, where psychiatric medication effectiveness may be impacted. Additionally, semaglutide impacts the gut microbiome, and we have increasing research linking the microbiome to affecting mood and mental health via the gut-brain axis. We know 95% of serotonin is made in the gut, so it makes sense that digestive distress, which is common with these drugs, could be negatively impacting mood.

 

·      The history of other weight loss drugs. This isn't the first "miracle weight loss cure" medication approved by the FDA. In the 1940's it was Amphetamine, AKA speed, which was found to be highly addictive. In the 90's, it was "Fen-phen," which was taken off the market due to causing heart valve problems. These types of drugs don't have a good track record.

 

·      Reinforcing problematic beauty ideals. The obsession with these drugs feeds the notion that being in a larger body is wrong, unhealthy, and something to be fixed. Our society places so much value on how our bodies look, and this focus on weight loss only increases the fixation with weight and shape.

 

·      Reinforcing problematic eating behaviors. These drugs are potent appetite reducers. There have been headlines about how GLP-1s "reduce food noise," essentially reducing how much someone thinks about food. A brain that has endured undernourishment, regardless of shape/size, will have increased thoughts about food. This is a survival mechanism, where our body does not know that we are self-imposing a caloric restriction. The body increases cravings and thoughts about food to encourage intake.  It makes sense to me that many folks who start these medications have likely dieted and or have a history of eating disorders. They likely had more "food noise" as their body and brain worked hard to keep them nourished (and alive) after periods of restriction. Other ways to "reduce food noise" include stopping dieting and working with a HAES® Registered Dietitian and/or Therapist.

 

·      The way they are being marketed as being a solution to weight stigma. This one really grinds my gears. Novo Nordisk is promoting "inclusive ob*sity care," claiming "…with approximately 2 out of 5 adults in the United States living with ob*sity, it's important that they feel seen and heard when seeking help from a health care provider. But sometimes, the fear of being judged may stop many from doing so. That's why we're on a mission to reduce bias and stigma for people living with ob*sity." They aren't trying to hide the fact that their motivation for reducing bias and stigma is to encourage people to see their providers to be prescribed these drugs. The solution to weight stigma is not eradicating people in larger bodies; it is challenging the deeply entrenched beliefs that living in a larger body is wrong and something to be fixed.

 

·      The reported lack of informed consent happening when prescribing. I have seen this in my practice, and have heard this from many other clinicians that clients are reporting they were not made aware that this medication is intended to be used for life, the side effects, the lack of long-term data, or the amount of weight loss to expect. I have heard people being told by their providers that it can be used to "jump start" weight loss and then be discontinued. The data doesn’t support this; we see weight regain starting at the 2-year mark of using the medication (the most extended study to date), and weight regain occurs rapidly once the drug is stopped. It is the duty of providers to review the risks and expected outcomes and give patients the choice to pursue other options.

 

·      The cost. These medications are very expensive. Ozempic costs around $935.77 per month ($11,229.24/year), and Wegovy $1,349.02 per month ($16,188.24/year). These costly drugs are contributing to America's already exorbitant healthcare costs. If you are thinking, "But what if these drugs are really expensive to make?" like I was, allow me to disappoint you! A March 2024 JAMA article reports the estimated cost of manufacturing injectable semaglutide to be $0.89- $4.73 per month. Talk about a profit margin!

 

See, this is turning into a book, so I will end it here. Every week I sit on this blog, there is something new in the headlines: counterfeit Ozempic, overdoses occurring with compound pharmacy versions of these drugs, drug shortages impacting people who take these medications for type 2 diabetes management, and now blindness?!

There is no judgment should you choose to take these types of medications. I sincerely hope that it is supportive to your health and well-being. Know that if you could use support with your relationship with food and body while on these medications, considering these medications, or as someone who does not want to take these medications, my door is open!

What are your thoughts, concerns, or experiences with semaglutide drugs? Leave a comment!