What is it?
Semaglutide is a compound belonging to a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists. The GLP-1 hormone is released in the gastrointestinal tract in response to eating. One role of GLP-1 is to prompt the body to produce more insulin, which reduces blood glucose (sugar). The compound semaglutide mimics the GLP-1 hormone, proving itself a powerful tool in treating Type 2 Diabetes (UCLA Health).
In higher amounts, GLP-1 reacts with the parts of the brain that reduce appetite and can signal a feeling of fullness, according to the Food and Drug Administration.
Semaglutide’s ability to produce insulin and reduce blood sugar made the compound a clear winner in Type 2 diabetic treatment. But as an appetite suppressant, semaglutide attracted an alternative audience seeking a different treatment — weight loss.
The Danish pharmaceutical company Novo Nordisk invented and developed semaglutide and have since released numerous drugs that sell under names such as Ozempic, Wegovy and Rybelsus. While some of these options are prescribed as antidiabetic medications, audiences have flocked to their weight loss properties (NYTimes).
Ozempic and Wegovy, both created and sold by Novo Nordisk, are under-the-skin drugs, meant to be injected once a week in the stomach, thigh or arm through a pen-like instrument. The FDA approved Ozempic only to lower blood sugar levels in adults with Type 2 diabetes, but is commonly prescribed for its off-label use — weight loss. Wegovy, on the other hand, has been approved by the agency to treat adults with weight loss (FDA).
For Ozempic, the beginning dose is 0.25 mg once a week for the first 4 weeks. According to Ozempic’s website, this will help give the body a chance to get used to the medicine. At Week 5, the health care provider will increase the dose to 0.5 mg once a week.
The injection method for Wegovy is similar. Wegovy comes in 5 different dose strengths. Users start Wegovy at a dose of 0.25 mg once a week and increase the dose
every 4 weeks until they reach the full dose of 2.4 mg. Each dose comes in a different color pen and is dispensed at the same areas on the body as Ozempic.
Rybelsus serves the same function as Ozempic, but is offered in oral tablet form to be taken by mouth, daily, thirty minutes before eating. Users will usually take 3 mg once a day for the first month, after which the dose will be raised to 7 mg, once a day. After this month, a health care provider would decide whether a dosage increase is beneficial (Health Line).
FDA Regulation
Semaglutide products are soaring in popularity, but there are currently just three FDA approved semaglutide products. The rest are prescribed and taken for off-label use.
Ozempic injection is approved to lower blood sugar levels in adults with Type 2 Diabetes, when paired with diet and exercise. It is also approved to reduce the risk of heart attack, stroke, or death in adults with Type 2 Diabetes and known heart disease. The FDA has not approved Ozempic as solely a weight loss drug.
However, Ozempic sales have not slowed for those simply seeking weight loss. It isn’t over the counter, but according to Healthline, patients may be able to get an off-label prescription for Ozempic from a healthcare professional. This usually involves a consultation and the health care provider deciding if they believe it’s safe and appropriate for a patient’s specific health needs.
Unlike Ozempic, Wegovy injection is approved by the FDA for weight loss circumstances. In 2021, the agency approved of the drug and its use to help adults and children aged 12 years and older with obesity. The drug is also meant to assist overweight adults who also have weight-related conditions, such as high blood pressure, high cholesterol, or Type 2 diabetes, to lose weight. The drug is to be paired alongside reduced calorie diet and increased exercise.
Similar to Ozempic, Rybelsus tablets are approved to lower blood sugar levels in adults with Type 2 Diabetes, in addition to diet and exercise. All three medications are only available with a prescription, and there are no approved generic versions (FDA).
Negative Side Effects
While undoubtedly effective, semaglutide drugs have left users with significant adverse side effects. Ozempic details its most common serious side effects on the drug’s warning label. They include:
● inflammation of your pancreas (pancreatitis). Stop using Ozempic® and call your health care provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.
● changes in vision. Tell your health care provider if you have changes in vision during treatment with Ozempic®.
● low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Ozempic® with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include: dizziness or Iightheadedness, blurred vision, anxiety, irritability or mood changes, sweating, slurred speech, hunger, confusion or drowsiness, shakiness, weakness, headache, fast heartbeat, and feeling jittery.
● kidney problems (kidney failure). In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems to get worse. It is important for you to drink fluids to help reduce your chance of dehydration.
● serious allergic reactions. Stop using Ozempic® and get medical help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue, or throat; problems breathing or swallowing; severe rash or itching; fainting or feeling dizzy; or very rapid heartbeat.
● gallbladder problems. Gallbladder problems have happened in some people who take Ozempic®. Tell your healthcare provider right away if you get symptoms which may include: pain in your upper stomach (abdomen), fever, yellowing of the skin or eyes (jaundice), or clay-colored stools.
The most common side effects of Ozempic® may include nausea, vomiting, diarrhea, stomach (abdominal) pain, and constipation.
Over 10,000 semaglutide-related adverse events were reported to the FDA’s Adverse Event Reporting System — a database that contains adverse event reports, medication error reports and product quality complaints submitted to FDA — through the 4th quarter of 2021. Semaglutide products were identified as suspect products for
gallbladder-related disorders in these reports, finding 7,538 adverse reports for Ozempic; 1,223 for Rybelsus, and 564 for Wegovy (Levin Law).
Gallbladder Warning
On its warning label, Ozempic warns that acute gallbladder diseases and Thyroid C-cell tumors can occur. However, until March 2022, the Ozempic warning label did not adequately warn patients or doctors about the risk of gallbladder disease, despite evidence arising that patients experienced such complications.
A series of published scientific studies and reports concluded that acute cholecystitis (gallbladder disease) and cholelithiasis (gallstones) was associated with therapy of GLP-1 receptors and drugs. In other words, Ozempic’s chemical makeup put users at higher risk of gallbladder related diseases, while the label issued no warning at the time (Lawsuit Information Center).
In one of these studies, Daniel Woronow, MD, and colleagues from the FDA in Silver Spring, Maryland found that 36 patients taking semaglutide between 2005 and 2016 developed acute gallbladder disease, three of whom died. In 42 percent of those cases, the gallbladder problems started within 90 days of first taking the drug treatment. Novo Nordisk added warning labels about gallbladder complications to the drug in March 2022 (Green Matters).
At this time, a class action lawsuit is forming to represent people who developed gallbladder problems after taking the drug. The legal issue is whether Novo Nordisk knew or should have known about the health risks the drug poses to users of their drug and neglected to warn doctors and patients of this risk.
Individuals who used Ozempic prior to the updated warning label including the gallbladder risks, and who developed gallbladder disease, gallstones, or have their gallbladder surgically removed, may be able to file a product liability lawsuit
and receive financial compensation.
Projectile Vomiting
Ozempic’s warning label advises users to stop using the drug if they experience stomach pain, sometimes accompanied by vomiting. Nausea is the most common side effect and up to 20% of people taking it for Type 2 diabetes reported nausea in clinical trials, according to GoodRx Health.
Nausea and vomiting is more likely the higher the dose of semaglutide. This is why the semaglutide dosage, whether in the form of Ozempic or Wegovy, is slowly increased across several weeks. While Ozempic says this is normal, vomiting accompanied with severe stomach pain could be cause to monitor kidney function (Good Rx Health).
Ozempic users experiencing this uncomfortable side effect take to Reddit discussion groups, hoping to find if their experience is normal. One user submitted her inability to control the vomiting after starting Ozempic. She wrote: “I had a green juice, and the green juice came out in the form of projectile vomiting…It was so bad that my sister thought I was choking on my own vomit… I just ended vomiting all over myself and feeling really shakey.”
The discussion forum flooded with relatable experiences and pieces of advice.
One user responded with: “This happened to me, I was taking .25 and would projectile vomit everyday.” Another replied: “I now keep barf bags in my car.”
Ozempic Face
In addition to the internal side effects of Ozempic, users who take the drug for its
cosmetic benefits are finding the slimming drug is doing its job a little too well. Unflattering effects have triggered the popular buzzword: Ozempic face.
Some users experience a gaunt, aged appearance in the face. Dr. Oren Tepper, a plastic surgeon in New York who was quoted in an Ozempic New York Times article, stated that when it comes to facial aging, fat is usually key to a more youthful appearance. “Ozempic face” is a hollowed, sagging, and more wrinkled appearance thanks to Ozempic’s ability to shave weight off the entire body.
Not only have Ozempic users found less flattering appearances in the face, but “Ozempic Butt” and “Ozempic Fingers” have earned buzzword status as well. Fat loss can occur in the butt, leading to a deflated, flat, and sagging appearance that users don’t typically desire. Users with “Ozempic Fingers” find that their jewelry and rings no longer fit, and their fingers and wrists more bony than before. The New York Post found that jewelers have reported women sizing down rings and bracelets, up to a shocking 150% compared to last year.
Sh*t the Bed Club
An even more unsightly effect of Ozempic, according to the Post, includes waking up with soiled sheets. Some users say they’ve joined a “sh*t the bed club,” due to the gastrointestinal effects of Ozempic. Semaglutide users congregate on the discussion forum Reddit, trying to sift through what is normal and what might be cause for alarm.
One comment on the discussion thread reads, “almost shit my pants today RUNNING for the bathroom when my constipation without warning, decided to identify as WWIII.” According to Insider, about 30% of Wegovy users have suffered from diarrhea, while 24% have experienced constipation.
Suicidal Ideation
On Monday, July 10th, the European Medicines Agency said it would undertake an official review of a number of obesity-treating and antidiabetic drugs after it was reported some patients experienced thoughts of suicide or self harm (CNBC).
The statement made by the EMA said that its safety committee was “currently evaluating the risk of suicidal thoughts and thoughts of self-harm in patients who used a semaglutide — or liraglutide — containing medicine for weight loss.” The call for this evaluation is the result of three case reports: two cases of suicidal thoughts, one following the use of Saxenda (a daily antidiabetic) and one following the use of Ozempic. The third case reported thoughts of self-injury with Saxenda.
Because suicidal thoughts are not listed as an effect of either drug administered by Novo Nordisk, the safety committee of the EMA will consider whether the review should be extended. According to the New York Post, the EMA has launched an investigation into all of Novo Nordisk’s weight loss treatments, not only Ozempic and Saxena, as well as any other medications that contain semaglutide or liraglutide.
Dangers of a high-cost Weight Loss Drug
Novo Nordisk, the Danish pharmaceutical company that originally developed semaglutide, holds a patent on the antidiabetic. Because of the patent, Novo Nordisk is able to charge whatever it wants and according to the Institute for Clinical and Economic Review, Novo Nordisk is grossly overcharging.
In an evidence report by the ICER titled Medications for Obesity Treatment: Effectiveness and Value, the nonprofit estimated that a fair price for the drugs, when considering the overarching health benefit, would be 44% to 57% cheaper than what they are currently sold for. In 2022, ICER issued an access and affordability alert for
semaglutide in the management of overweight and obesity, signaling stakeholders and policy makers.
Antidiabetic drugs like Ozempic are not covered for obesity, so most health insurances cover it for treating diabetes only. While Wegovy is FDA approved for treating weight loss, a month’s supply costs about $1,300 out of pocket. Ozempic is about the same. Users might splurge for the initial weight loss, but can’t afford to stay on the medication for the long term. But when people stop taking it, there’s often a rebound weight gain that becomes even more insurmountable than before. A study published by Diabetes, Obesity and Metabolism found that users regain most of their lost weight within a year of stopping the medication (Wilding et al.)
Either due to the high cost or ongoing shortages, people are seeking alternatives to Ozempic and Wegovy, according to NBC. One way to find these copycat drugs is through compounding pharmacies.
Compounding “is the process of combining, mixing, or altering ingredients to create a medication tailored to the needs of an individual patient,” the FDA says. “Compounding includes the combining of two or more drugs.” So, pharmacies known to carry and distribute these copycat drugs are called compounding pharmacies.
“When a drug is in shortage, compounders may be able to prepare a compounded version of that drug if they meet certain requirements of the Federal Food, Drug, and Cosmetic (FD&C) Act,” the FDA says, but the agency doesn’t review these compounded versions for safety, effectiveness or quality. So while semaglutide may be approved by the FDA, a compounded version of it does not undergo the same monitoring or testing.
According to an article published by NBC Health News, physicians don’t know where compound pharmacies are getting information on semaglutide. Novo Nordisk, the patent holder and sole distributor of Ozempic and Wegovy, said in a statement that it does not provide the ingredients to pharmacies, and compound semaglutide might not be semaglutide at all.
Pharmacies aren’t always transparent about how they’ve created or sourced a drug, according to Dr. Chris McGowan, an owner of a weight loss clinic and a source for the NBC article. Further, it’s possible semaglutide sodium is being sold, a cheaper and modified version of the compound intended for research only. Semaglutide sodium, however, isn’t approved by the FDA, and sale of it would be wholly illegal (NBC).
The FDA says that it has received reports of adverse events in people who used compounded semaglutide and that patients “should not use a compounded drug if an approved drug is available.”
Growing Popularity
It is not uncommon for health care providers to prescribe medications for “offlabel” use, and Ozempic is a clear cut example. “Off-label” use is taking a medication for a different purpose than what it is explicitly intended for. Taking Ozempic for weight loss, when it is approved and intended for Type 2 Diabetes, is an example.
The FDA states that when taking a drug for its approved use, you can be sure the agency has conducted a careful evaluation of its benefits and risks for that use, the decision to use the drug is supported by strong scientific data, and there is approved drug labeling for healthcare providers on how to use the drug safely and effectively for that use (FDA).
However, the FDA also states that once it has approved a drug, healthcare providers may prescribe that drug for unapproved uses, if they judge that it is medically appropriate for their patient. This is not uncommon practice, but as it becomes increasingly available, it also becomes increasingly popular — especially when celebrities and social media get a hold of it.
Elon Musk, tech magnate, was asked in a tweet, “Hey, @elonmusk what’s your secret? You look awesome, fit, ripped & healthy. Lifting weights? Eating
healthy?” To which Musk responded “Fasting…And Wegovy”.
At this year’s Academy Awards ceremony, host Jimmy Kimmel joked, "Everybody looks so great. When I look around this room, I can't help but wonder 'Is Ozempic right for me?'" Actress and comedian Chelsea Handler admitted to taking the weight loss drug without fully understanding it. After finding out the drug was intended for Type 2 diabetics, the actress claimed she immediately stopped.
Actress Amy Schumer also admitted to beginning Ozempic but stopped after feeling so sick, she couldn’t play with her son. She then criticized other celebrities, without naming any specifics, for denying or not being forthcoming about Ozempic usage. Tik Tok creator and model Remi Bader revealed she took Ozempic after being prescribed by her doctor, but claimed she gained double the weight back. Other celebrities such as Julia Fox, Kyle Richards, Mindy Kaling and others have denied using Ozempic, despite allegations (Elle).
On the Horizon
Novo Nordisk is working towards an oral form of semaglutide, as published in their two funded studies on July 25, 2023. The first study demonstrated that 50 milligrams of semaglutide when taken orally each day is about as effective as the weekly Wegovy shots that reduce weight in overweight or obese people. Wegovy shots contain just 2.4 milligrams of semaglutide (NYTimes).
The second study aimed to prove the efficacy of oral semaglutide for people with Type 2 diabetes. Participants were divided into three groups, each given either 14-milligram, 25-milligram, or 50 milligram doses daily, by mouth. The higher the dose, the more weight lost (NYTimes).
However, it also seemed that the higher the dosage, the more side effects were experienced. The study found that adverse events were reported by 404 (76%) participants in the oral semaglutide 14 mg group, 422 (79%) in the 25 mg group, and 428 (80%) in the 50 mg group. Gastrointestinal disorders, which were mostly mild to moderate, occurred more frequently with oral semaglutide 25 mg and 50 mg than with 14 mg (Aroda et al.).
No new safety concerns were revealed, which one might assume will lead to the introduction of an oral Ozempic and Wegovy supplement. However, oral semaglutide has already been in circuit. Rybelsus, as mentioned above, is an FDA approved drug for adults with Type 2 diabetes, but the semaglutide dosage is comparably lower and according to the New York Times, Rybelsus is less effective than Ozempic and Wegovy.
