Semaglutide for Weight Loss: How It Works and Compares to Other Weight-Loss Medications

In June 2021, the FDA approved semaglutide (Wegovy), a once-weekly injection for weight loss in adults. But semaglutide was making headlines even before its approval. That’s because people using it during clinical trials lost 15% to 18% of their starting body weight. This was more than other weight-loss medications on the market.

Since then, semaglutide has been approved for weight loss in adolescents ages 12 and older and heart protection in certain people with heart disease. It's also been approved for certain adults with metabolic dysfunction-associated steatohepatitis (MASH), a type of liver disease. And it’s being researched for a growing list of other potential uses, too.

So, is using semaglutide for weight loss right for you? While it may work better than some other weight-loss medications, there are other factors to consider. Let’s review what you should know about semaglutide.

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What is semaglutide?

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It was originally approved in 2017 as Ozempic, a once-weekly injection for adults living with Type 2 diabetes. The FDA approved Rybelsus, a once-daily pill version of semaglutide, a few years later.

People using semaglutide for Type 2 diabetes also tend to lose weight as an additional benefit. Because of this, the manufacturer studied the medication specifically for weight loss, but at a higher dose. This led to the approval of Wegovy in 2021 — the first once-weekly GLP-1 receptor agonist for weight loss.

Semaglutide (as Wegovy) has been approved for cardiovascular benefits in adults with a larger body size who have heart disease. If you have heart disease, Wegovy can help lower your risk of serious cardiovascular problems. It’s currently the only weight-loss medication approved for this use.

Most recently, Wegovy was also approved to treat adults with MASH who have moderate-to-advanced liver scarring (fibrosis) — but not cirrhosis — along with a reduced-calorie diet and increased physical activity.

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Good to know: There are compounded and research-grade versions of semaglutide on the market. These are not the same as the FDA-approved semaglutide products sold as Wegovy, Ozempic, or Rybelsus. The safety and effectiveness of unapproved versions of semaglutide haven’t been confirmed.

How does semaglutide work for weight loss?

Semaglutide mimics GLP-1, an incretin hormone that plays a role in appetite and digestion. It’s thought to work in a few different ways to help you lose weight. These include:

• Slowing the movement of food out of your stomach (gastric emptying)

• Targeting areas of the brain that help regulate appetite and fullness

• Reducing cravings for certain foods, such as salty snacks or sweets

Certain semaglutide effects, such as slowed gastric emptying, may lessen over time. Other semaglutide effects, such as appetite reduction, only last as long as you’re using the medication.

Who should take semaglutide for weight loss?

Before starting semaglutide for weight loss, discuss the potential benefits and risk of treatment with your healthcare team. That’s because semaglutide isn’t right for everyone. It’s also a long-term commitment since rebound weight gain is possible if you stop using it.

For weight loss, semaglutide was studied in certain adults and adolescents who met established body mass index (BMI) criteria. As Wegovy, it’s currently approved for the following groups:

• Adults and adolescents ages 12 and older who are considered to be obese

• Adults who are considered to be overweight and have at least one weight-related health condition, such as high blood pressure or high cholesterol

Semaglutide is sometimes prescribed off-label for people who don’t meet the above criteria. This means the FDA hasn’t confirmed that semaglutide is safe and effective for these uses. Even so, your healthcare team may decide that semaglutide is appropriate for you.

EXPERT PICKS: WHAT TO READ NEXT

• GLP-1 savings guide: Learn about ways to save on glucagon-like peptide-1 (GLP-1) medications, like Wegovy (semaglutide), with GoodRx discounts, copay savings cards, and more.

• Is semaglutide in shortage? Learn more about the latest status of the semaglutide shortage, including the availability of Ozempic (semaglutide) and Wegovy.

• Wegovy vs. Zepbound: Wegovy and Zepbound (tirzepatide) are both once-weekly injections for weight loss. Here’s how they compare.

What is the semaglutide dosage for weight loss?

Semaglutide is injected once a week, on the same day each week. It can be injected at any time of day, without regard to meals. 

You’ll typically start with a low semaglutide dose and work your way up every 4 weeks until reaching 2.4 mg once weekly — the target maintenance dose. But if you can’t tolerate the 2.4 mg dose, you may be instructed to inject 1.7 mg weekly as your maintenance dose. 

This semaglutide dosage schedule is meant to help manage potential side effects. If you’re unable to tolerate semaglutide, your prescriber may lower your dose or have you stop using it.

But what happens if you miss your semaglutide dose? Don’t panic — there are ways to get back on track. If your next scheduled dose is more than 2 days (48 hours) away, inject your missed dose and resume your usual schedule. But if your next dose is within 2 days, skip the dose you missed and start again on your regular injection day.

How to inject semaglutide

Wegovy, the semaglutide product approved for weight loss, is available as a single-use injection pen. Your dose is already pre-set for you and the needle is already attached to the pen. Each pen contains one dose, so you’ll throw it away after your injection. Here are some general steps to follow:

• Choose your injection site. Inject your dose just under the skin (subcutaneously) of your abdomen, upper arm, or thigh. If you choose the upper arm, it’s best to have someone else give you the injection. Rotate injection sites each week to help limit injection site reactions.

• Prepare the site. Clear the area with an alcohol swab and let it dry. Don’t blow on the area to make it dry faster.

• Remove the pen cap. Do this right before you’re ready to inject. After removing the cap, you won’t see a needle since it’s hidden inside the needle cover.

• Inject your dose. Push the pen firmly against your skin, which will trigger the injection. You should hear a “click” and the yellow bar should start moving, followed by a second click. Continue holding the pen here until the bar stops.

• Dispose of the pen. Throw your used pen into a sharps container.

Keep in mind that Ozempic, another semaglutide injection, is sometimes prescribed off-label for weight loss. The Ozempic injection pen works differently compared to the Wegovy pen. You’ll also follow different instructions if you’ve been prescribed compounded semaglutide, which usually comes in a vial with syringes.

What do we know about semaglutide side effects?

Gastrointestinal side effects tend to happen most frequently with semaglutide for weight loss. They’re usually more pronounced when you first start semaglutide and after your dose is increased. Examples of common semaglutide side effects include:

• Nausea and vomiting

• Diarrhea

• Stomach pain

• Constipation

• Headache

• Fatigue

While rare, semaglutide has been linked to potentially serious side effects. These include:

• Pancreatitis (inflamed pancreas)

• Gallbladder problems

• Kidney damage

• Low blood glucose (sugar)

• Fast heart rate

• Worsening eye problems in people with diabetes

The FDA has also issued a boxed warning for semaglutide and its possible increased risk for thyroid C-cell tumors. There are no reports of humans developing these tumors from semaglutide, but it was reported in animal studies.

Can semaglutide interact with other medications?

Yes. Semaglutide can interact with diabetes medications, especially insulin and those that increase insulin release (such as sulfonylureas). These combinations can increase the risk of your blood sugar levels dropping too low (hypoglycemia).

Since semaglutide slows gastric emptying, it may potentially interfere with how your body absorbs oral medications. As mentioned above, this effect may only be a concern within the first several months of treatment. Your healthcare team can determine which interactions potentially affect you and how to manage them.

It’s also a good idea to avoid or limit alcohol while taking semaglutide. Alcohol may worsen certain side effects, sabotage weight-loss progress, and offset cardiovascular benefits.

How does semaglutide compare to other weight-loss 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 15% of their initial body weight on average.

So, how does semaglutide stack up against other weight-loss medications?

Semaglutide vs. common weight-loss pills

There are several oral weight loss pills available. Oral weight-loss medications tend to be less expensive than the injectable options. But you may not lose as much weight.

Phentermine: Phentermine (Adipex-P) is a popular oral weight-loss medication that has been around since 1959. It’s approved for short-term use (up to 12 weeks), and it’s inexpensive. However, it’s possible to develop a tolerance to phentermine where it’s no longer working for you. Plus, it’s a controlled substance, meaning that it has a risk of dependency and misuse.

Qsymia: Phentermine is also available in combination with topiramate under the brand name Qsymia. Compared to phentermine alone, Qsymia is approved to be taken 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). But unlike other weight-loss medications, you have to enroll in Qsymia’s mandatory risk management program if you’re able to get pregnant. This is required since Qysmia can harm a growing fetus.

Contrave: 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. Contrave also has several drug interactions to consider.

Liraglutide vs. semaglutide

Liraglutide (Saxenda) was the first GLP-1 receptor agonist approved for weight loss. It’s a short-acting injection that needs to be administered once a day. In clinical studies, people lost an average of about 8% of their starting body weight after 56 weeks.

Semaglutide, by contrast, stays in the body longer and is injected once a week. It was the first once-weekly GLP-1 approved for weight loss and has shown greater weight loss results in clinical trials.

Both liraglutide and semaglutide are approved for use in adults and adolescents ages 12 and older. But only semaglutide is also approved to lower the risk of serious cardiovascular problems in certain people, with or without diabetes.

Tirzepatide vs. semaglutide

Tirzepatide (Zepbound) is a once-weekly injection approved for adults living with moderate-to-severe obstructive sleep apnea as well as for adult weight loss. It’s also sold as Mounjaro to treat adults living with Type 2 diabetes. Like semaglutide, tirzepatide mimics GLP-1. But it also mimics glucose-dependent insulinotropic polypeptide (GIP), which can have additional benefits.

During a trial comparing both medications for weight loss, people using tirzepatide lost more weight (20% of their starting weight) than those using semaglutide (14%). But unlike semaglutide, tirzepatide isn’t approved for cardiovascular benefits yet.

How to save on semaglutide

There are ways to save on semaglutide, which is available as brand-name Wegovy. 

• Save with a manufacturer savings card: If you have commercial insurance, you may be eligible to pay as little as $0 for Wegovy using a savings card from the manufacturer.

• Save with GoodRx: GoodRx coupons can also help you save on your prescription. The price of Wegovy is as low as $499 per month with GoodRx.

• Save with direct pharmacy options: Get Wegovy delivered to your home for as low as $499 per month through NovoCare Pharmacy.

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Written by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

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