Semaglutide: The First New FDA-Approved Weight Loss Medication Since 2014

Written by Alyssa Billingsley, PharmD | Reviewed by Joshua Murdock, PharmD

Updated on January 9, 2023

Key takeaways:

• Semaglutide (Wegovy, Ozempic) is the first once-weekly medication in its class that’s FDA-approved to help with chronic weight management. It works best when used in combination with a healthy diet and exercise.
• The largest clinical trial showed that adults taking semaglutide lost an average of almost 15% of their initial body weight — about 12% more than those who didn’t take the medication. Adolescent clinical trials showed an average weight loss of 16%.
• There are many ways to save on Wegovy, the version of semaglutide approved for weight loss. If you’re eligible, a manufacturer savings card can help you access Wegovy.

Table of contents

     About semaglutide

     How it works

     Dosing and administration

     Side effects

     Interactions

     Comparison

     How to save

     Bottom line

     References

What is semaglutide?

Semaglutide is an injectable glucagon-like peptide-1 (GLP-1) agonist that’s administered once weekly. It was originally approved in 2017 — at a lower dose under the brand name Ozempic — to help control blood sugar in Type 2 diabetes. People taking Ozempic for blood sugar control also tend to lose weight as an additional benefit. 

Because of this, Novo Nordisk studied the medication in people without Type 2 diabetes, but at a higher dose. Now, semaglutide (under the brand name Wegovy) is FDA approved for weight loss. It can be used by adults with a body mass index (BMI) greater than or equal to 30 mg/kg² alone or 27 mg/kg² with at least one weight-related condition (e.g., high blood pressure, high cholesterol, Type 2 diabetes).

Semaglutide is also approved for chronic weight management in adolescents ages 12 and older. Eligibility is based on having an initial BMI at or above the 95th percentile for sex and age.

Semaglutide should be used in combination with lifestyle changes, including a healthy diet and exercise.

How does semaglutide work for weight loss?

GLP-1 is an incretin hormone that plays a role in your appetite and digestion. Incretins — hormones released by your digestive tract — are sent out by your body after you’ve eaten a meal. They help lower your blood sugar by triggering insulin release and blocking sugar production. They also slow down how quickly food leaves your stomach (called gastric emptying).

The result of these actions causes you to feel full — lowering your appetite and causing you to lose weight. Medications like GLP-1 agonists are referred to as incretin mimetics since they “mimic” these effects.

As mentioned above, GLP-1 agonists, like semaglutide, were originally used to treat Type 2 diabetes. This was due to their blood sugar-lowering effects. However, the weight loss side effect has been shown to benefit people without Type 2 diabetes as well.

How is semaglutide dosed?

Semaglutide is available as a single-use injection pen. This means that your dose is already pre-set for you, and that you’ll discard the pen after your dose. 

You’ll give yourself the injection once a week, on the same day each week. It can be given at any time of day, and you can take it with or without food.

 Semaglutide is typically injected just under the skin (subcutaneously) in your abdomen, upper arm, or thigh. Avoid injecting the medication into the same spot every time — change your injection site with each dose. But injecting in the same body area (e.g., thigh) is OK as long as you’re rotating sites within the area each time.

Since semaglutide slows down how quickly food leaves your stomach, you may experience side effects like nausea and vomiting. Once you get started on the medication, your healthcare provider will slowly increase your dosage every 4 weeks. This can help make these effects more manageable. 

The target dose for both adolescents and adults is 2.4 mg once weekly. Before reaching the target dose, a typical dosing schedule may look like:

• Month 1: 0.25 mg once weekly for the first month
• Month 2: 0.5 mg once weekly for the second month
• Month 3: 1 mg once weekly for the third month
• Month 4: 1.7 mg once weekly for the fourth month
• Target maintenance dose: 2.4 mg once weekly

 Some people may not be able to reach or tolerate the target dose due to side effects. If this is the case, your healthcare provider may wait another month before increasing your dose. However, they may have you stop the medication if you’re unable to reach or stay on the target dose.

What do we know about semaglutide side effects?

As introduced earlier, gastrointestinal (GI) side effects tend to happen most frequently when taking this medication. The most common are nausea, diarrhea, and vomiting. You may experience these effects more strongly when your healthcare provider increases your dose.Additional common side effects can include:

• Constipation
• Stomach pain
• Headache
• Fatigue
• Indigestion
• Dizziness
• Bloating
• Burping

Serious side effects

In some cases, semaglutide may cause more serious side effects. The medication has a boxed warning — the FDA’s most serious warning — for a potential risk for thyroid C-cell tumors. This risk has been seen in animal studies, but it hasn’t been confirmed in people. Because of this, you shouldn’t take semaglutide if you have a personal or family history of certain thyroid tumors.

Other serious side effects can include:

• Pancreatitis (inflamed pancreas)
• Cholelithiasis (gallbladder disease)
• Kidney damage
• Low blood sugar (hypoglycemia)
• Allergic reactions (including swelling of the face, tongue, or throat; difficulty breathing)
• Certain eye problems in people with Type 2 diabetes
• Fast heart rate

Suicidal thoughts and behaviors are another risk listed on the medication’s labeling because it’s been reported with other weight loss medications. Let your healthcare provider know right away if you’re experiencing any changes in mood or behavior, or if you’re having suicidal thoughts.

Can semaglutide interact with other medications?

Since semaglutide can lower your blood sugar, it can interact with other blood sugar-lowering medications. Examples include insulin and medications that cause insulin to be released, like sulfonylureas. Combining these medications can result in dangerously low blood sugar levels.

If you’re taking one of these medications, your healthcare provider may lower the other medication’s dose while starting you on semaglutide. And as a general rule, it’s important to diligently monitor your blood sugar if you have Type 2 diabetes. This is especially the case before and during treatment to ensure that your readings stay within a safe range.

Another potential interaction is with oral medications. Semaglutide slows down how quickly food leaves your stomach. This may affect how certain oral medications are absorbed by your body when they’re taken together. Your healthcare provider can determine which interactions potentially affect you and how to manage them

How does semaglutide compare to other weight loss medications?

One of the reasons there’s a lot of buzz around semaglutide is the amount of weight people lost during clinical trials. Typically, we tend to see an average of 5% to 10% weight loss with other medications. 

The largest clinical trial studying semaglutide in adults showed an average weight loss of about 15% of initial body weight over 68 weeks (almost 16 months). Over the same length of time in another study, adolescents lost 16% of their initial body weight on average.

Oral weight loss medications tend to be less expensive than the injectable options, but you may not lose as much weight. Let’s review a few of the more popular weight loss medications and how they compare to semaglutide.

Oral medications

Phentermine is a popular oral weight loss medication that has been around since 1959. It’s approved for short-term use (a few weeks), and it’s inexpensive. However, it’s possible to develop a tolerance to the medication where it’s no longer working for you. And it’s a controlled substance.

Phentermine is also available in combination with topiramate under the brand name Qsymia. Compared to phentermine alone, Qsymia can be used for a longer period of time. Study results have shown average weight loss ranging from about 5% (at lower doses) to around 10% (at higher doses). 

Contrave (bupropion/naltrexone) is another medication used for weight loss. One study showed that people taking Contrave in combination with diet and exercise lost an average of about 9% of their baseline body weight after 56 weeks. This is compared to the largest semaglutide trial, where participants receiving the medication lost an average of almost 15% of their baseline body weight after 68 weeks.

Injectable medications

Liraglutide (Saxenda), a once-daily injectable GLP-1 agonist, was the first medication in its class to be approved for weight loss. It’s short-acting, which is why you need to administer it every day. It has also been shown to provide an average weight loss of about 8% from baseline body weight.

Semaglutide, on the other hand, works longer in your body. So, it’s only given once a week. This makes semaglutide the first once-weekly GLP-1 agonist approved for weight loss — with better results.  Both liraglutide and semaglutide are approved for use in adults and adolescents ages 12 and older.

Medications being studied for weight loss

Tirzepatide (Mounjaro) is a new medication that was approved in May 2022 for Type 2 diabetes.  Like semaglutide, it mimics GLP-1. But it also mimics another incretin called glucose-dependent insulinotropic polypeptide (GIP). While tirzepatide has similar effects as semaglutide, it’s the first medication in its class.

Tirzepatide was compared to semaglutide in a head-to-head clinical trial in people with Type 2 diabetes. It was more effective for long-term blood sugar control, and people taking it lost more weight compared to semaglutide.  

While tirzepatide isn’t currently approved for weight loss, promising results from a phase 3 trial for this use were published in July 2022. The FDA has since given the medication Fast Track designation, speeding up the time it may take for approval. It’s possible that we’ll see tirzepatide approved for weight loss in the near future.

How to save on semaglutide

There are ways to save on semaglutide, which is available as brand-name Wegovy. For example, a copay savings card can help make your prescription more affordable. If you have commercial insurance, you may be eligible to pay as little as $25 for Wegovy using a savings card from the manufacturer.

The bottom line

Semaglutide is an FDA-approved injectable weight loss medication. Compared to other medications on the market, it may help you lose more weight. 

It takes a few months to reach the target dose, and you may experience side effects like nausea, vomiting, and diarrhea. But this is typically managed by slowly increasing your dose over time.

Talk to your healthcare provider to learn more about semaglutide for weight loss. They can recommend the best chronic weight management option for you.

References

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Jastreboff, A. M., et al. (2022). Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine.

Jin, J. (2015). Medications for weight loss: Indications and usage. Journal of American Medical Association.

Lonneman Jr., D. J., et al. (2013). Phentermine/topiramate extended-release capsules (Qsymia) for weight loss. P & T.

Nauck, M. A., et al. (2018). Incretin hormones: Their role in health and disease. Diabetes, Obesity and Metabolism.

Novo Nordisk A/S. (2020). Novo Nordisk files for US FDA regulatory approval of once-weekly semaglutide 2.4 mg for weight management. GlobeNewswire.

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Vivus LLC. (2022). Qsymia [package insert].

Wadden, T. A., et al. (2012). Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: The COR-BMOD trial. Obesity.

Weghuber, D., et al. (2022). Once-weekly semaglutide in adolescents with obesity. New England Journal of Medicine.

Wilding, J. P. H., et al. (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine.