Introduction
If you know anyone who recently slimmed down after struggling to lose weight, he/she might be on Ozempic. The drug has been on the lips of thousands of people looking to shed pounds. If Novo Nordisk developed Ozempic’s active ingredient semaglutide in 2012, when did it receive FDA approval? What about its sister brands Wegovy or Rybelsus? In this article, we look back at semaglutide’s FDA approval and the clinical trials that led to its release.
Semaglutide: A review
Many are familiar with Ozempic, but how exactly does its active ingredient, semaglutide, work? How is it so effective in helping people lose weight?
In our gut is a hormone, glucagon-like peptide-1 or GLP-1. It’s responsible for triggering the pancreas to release the hormone insulin whenever our blood sugar levels are too high.
Now, semaglutide is a glucagon-like peptide-1 receptor agonist, or GLP-1 Ra. It mimics the function of GLP-1, kicking into action to prompt the production of insulin when blood glucose is elevated.
In addition, semaglutide also delays gastric emptying or the process where food exits the gut and enters the small intestine. Because people tended to feel fuller for longer, they had fewer cravings and didn’t eat as much, losing weight. At the same time, semaglutide also signals to the brain that you’re full.
When was semaglutide approved?
Before we dive into the history of semaglutide’s approval, let’s talk about its three different brands: Ozempic, Wegovy, and Rybelsus.
Ozempic and Rybelsus both treat type 2 diabetes, while Wegovy treats obesity.
Although they have different designs, essentially, they are all semaglutide and offer the same therapeutic benefits. Even if Novo Nordisk markets only Wegovy to obese patients, many healthcare providers prescribe Ozempic or Rybelsus off-label for weight loss.
Semaglutide FDA approvals
Since semaglutide has three different brands, they secured three separate FDA approvals.
The first semaglutide to receive FDA approval was Ozempic, in 2017, for improving blood sugar in adults with type 2 diabetes. The FDA gauged the results through its reduction in HbA1c, which measures a patient’s average blood sugar level over 2-3 months.
Ozempic comes as a liquid solution in an injectable dosing pen, which you administer subcutaneously (under the skin). You can administer it in three different injection sites, namely the 1) abdomen, 2) thigh, or 3) upper arm.
Ozempic’s clinical trials
Novo Nordisk conducted 12 clinical trials to test the safety, efficacy, and tolerability of Ozempic. In seven of these, patients received either Ozempic or a placebo. Meanwhile, in five of these, patients received Ozempic or another antidiabetic medication.
In another trial, patients with type 2 diabetes at high risk for cardiovascular problems received either Ozempic or a placebo. Overall, Ozempic successfully reduced the HbA1c levels, as well as participants’ body weight versus placebo.
In 2020, the FDA approved a new indication for Ozempic based on its significant reduction of the risk of major cardiovascular events. This includes heart issues like heart attack, stroke, or death in adults with type 2 diabetes and known heart disease.
Rybelsus
Rybelsus was the second semaglutide brand to receive FDA approval. In 2019, the FDA approved it for blood sugar control in adults with type 2 diabetes, with diet and exercise. The drug was the first GLP-1 receptor agonist to receive FDA approval that does not need to be injected.
Rybelsus’ clinical trials
Novo Nordisk conducted several clinical trials to test the safety, efficacy, and tolerability of Rybelsus. Two of these compared Rybelsus to a placebo, and the others compared Rybelsus versus other injectable GLP-1s.
In the placebo trials, Rybelsus significantly reduced HbA1c and reduced body weight of participants versus those in the placebo group.
Wegovy
Wegovy received FDA approval on June 4, 2021. It received approval for chronic weight management in adults with obesity or overweight adults with at least one weight-related condition. This was in addition to a lower-calorie diet and increased physical activity. Some examples of these weight-related conditions are type 2 diabetes, high blood pressure, or high cholesterol.
Wegovy comes in injectable dosing pens. You must administer it subcutaneously, meaning, under the skin.
The drug’s approval marked an important time in medicine. It was the first weight management drug with FDA approval since 2014 for adults who are obese or overweight.
Dosage and administration
Proper dosage, administration, and storage of semaglutide are key to ensuring it is working at its best. Your healthcare provider will start you on a low dose, gradually increasing this until you reach a maintenance dose. This is to allow your body to adjust to the drug.
You administer Ozempic and Wegovy once weekly regardless of meals. For Rybelsus, meanwhile, you take it once daily on an empty stomach.
The best time to take semaglutide is according to the dosage schedule of its manufacturer. It’s important that you follow the specific steps every time you administer semaglutide to ensure its optimum efficacy.
In addition, your healthcare provider should be able to demonstrate how to properly administer the medicine. More importantly, he/she can address any questions or clarifications you may have.
For best results, it is best to take semaglutide along with a healthy diet and exercise.
Missed doses
If you miss a dose of Ozempic, take the missed dose within five days after the missed dose. Meanwhile, if it has been over five days, skip the missed dose and take your next dose according to schedule.
If you miss a dose of Wegovy and the next dose is over two days away, take the missed dose ASAP. On the other hand, if the next dose is less than two days away, skip the missed dose and take the next scheduled dose. If you miss a dose for more than two weeks, use it on the next scheduled day of the dose. You may also want to consult your doctor about restarting the treatment.
For missed Rybelsus doses, just take the next dose the following day.
It’s important that you adhere to the prescribed schedule of taking semaglutide. This ensures that a consistent level of medication is in your bloodstream.
Side effects of semaglutide
Yes. Just like any other drug, semaglutide has potential side effects. Thankfully, though, these are generally mild and can be managed with the help of your doctor. Also, the more serious adverse reactions are rare.
Gastrointestinal reactions account for 10% or more of semaglutide’s side effects. These include:
- nausea (up to 44% of cases),
- diarrhea (up to 30%),
- vomiting (up to 24%),
- constipation (up to 24%),
- abdominal pain (up to 20%),
Other common side effects of semaglutide which occur in 1 to 10% of cases include indigestion, belching, gassiness, gastroenteritis, or gastritis. Gastroenteritis is a short-term infection and inflammation of the digestive system, while gastritis is the inflammation of the stomach lining.
The supply problem
Because of semaglutide’s popularity, it led to a major supply issue in late 2023, affecting Ozempic and Wegovy. This shortage is still ongoing as of this writing in February 2024.
Semaglutide manufacturer Novo Nordisk admitted a “short-term [Wegovy] stock-out” in the US through December due to demand surpassing supply capacities.
Currently, semaglutide is sold in the following: Australia, Belgium, Canada, France, Germany, Japan, Netherlands, Switzerland, the US, and the UK.
Because of the clamor for Ozempic and Wegovy, Novo Nordisk recorded its highest-ever profits. As a result, it was Europe’s most valuable company in September 2023.
The shortage problem will likely persist for several more years. Nevertheless, Wall Street predicts the demand will slow down in 2024 with more treatments becoming available on the market.
As consumers grapple with the shortage, healthcare providers have been turning to alternatives to treat type 2 diabetes and obesity. This includes Trulicity (dulaglutide), Victoza (liraglutide), Bydureon (exenatide), Rybelsus (semaglutide), Adlyxin (lixisenatide), and Byetta (exenatide).
Over 650 million people are suffering from obesity worldwide, and around 480 million, meanwhile, have type 2 diabetes.
FDA warns against the use of compounded semaglutide
You might have also already heard about compounded semaglutide. These are versions that still contain semaglutide, but with the addition of other ingredients, such as vitamins.
While the FDA has approved some drugstores to custom-mix variations of semaglutide, reports have cited adverse effects from these. Novo Nordisk and Eli Lilly have also reported impurities in the compounded medications.
Other reports noted that salt forms of semaglutide, such as semaglutide sodium and semaglutide acetate, were being used by compounders.
Compounded semaglutide offers a cheaper alternative for patients to get access to semaglutide. However, people need to make sure that they’re getting it from an outsourcing facility or a state-licensed pharmacy. If you are buying semaglutide online, make sure you are purchasing from a valid and reputable online pharmacy.
What’s next for semaglutide?
In 2024, six obesity clinical trials will be completed. These studies aim to support the development of semaglutide, monoacylglycerol acyltransferase 2 (MGAT2) inhibitors, and calcitonin gene-related peptide (CGRP) inhibitors.
MGAT2 inhibition has been linked to weight loss through the control of gut hormone regulation and energy expenditure. CGRP levels, meanwhile, are typically higher in people with obesity.
Novo Nordisk has a patent on semaglutide which will end in 2032. Until then, it can dictate the drug’s price, according to the nonprofit Institute for Clinical and Economic Review (ICER).
When the patent ends, semaglutide can be manufactured by other companies at lower-priced generic versions.
Conclusion
Although semaglutide was developed in 2012, Ozempic, Rybelsus, and Wegovy received FDA approvals in 2017, 2019, and 2021, respectively.
The FDA approvals follow positive results of their clinical trials. Semaglutide was found to significantly reduce blood sugar levels as well as body weight.
Amid the drug’s massive popularity came a serious supply issue, which will likely persist for several more years.
The FDA warns against the purchase of compounded semaglutide, a cheaper alternative. Some compounders use unsafe salt versions of semaglutide such as semaglutide sodium and semaglutide acetate.
Glossary of terms:
- Glucagon-like peptide-1 (GLP-1) is a gut-based hormone involved in the secretion of insulin to lower blood sugar levels typically elevated after meals.
- GLP-1 Ra: Glucagon-like peptide-1 receptor agonists mimic the actions of GLP-1.
- HbA1c (Hemoglobin A1c): A test used to measure the average blood sugar over two to three months
