A: In June 2021, the FDA approved semaglutide (Wegovy), a once-weekly injection, for weight loss in adults when used in combination with a healthy diet and routine exercise.

Before its approval, semaglutide had made headlines when the manufacturer reported participants had lost 15% to 18% of their starting body weight during clinical trials. Since then, it has also been approved for weight loss in adolescents ages 12 and older. What’s more, semaglutide now has proven cardiovascular benefits for certain people, too.

So, is 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.

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

People taking 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 agonist for weight loss.

More recently, semaglutide (as Wegovy) has been approved for cardiovascular benefits in adults with heart disease who are considered overweight or obese. If you have heart disease, Wegovy can help lower your risk of serious cardiovascular problems. It’s the only weight-loss medication.approved for this use.

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 are unknown.

• Knowing the risks: Compounded products can help people access certain medications that are in shortage. But before giving compounded semaglutide a try, it’s a good idea to understand the potential risks.
• What it’s like: Are you considering Wegovy for your weight-loss journey, but you’re unsure what to expect? Hear from real people as they describe what it’s like to take Wegovy and offer tips for others who are considering it.
• A natural boost: Medications like Wegovy work by mimicking the effects of a gut hormone called glucagon-like peptide-1 (GLP-1). But did you know that there are foods and supplements that can increase GLP-1 naturally?

A: 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:

• Slows the movement of food out of your stomach (gastric emptying)
• Targets areas of the brain that help regulate appetite and fullness
• Reduces 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.

A: Before starting semaglutide for weight loss, it’s important to 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

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.

A: Semaglutide is injected once a week, on the same day each week. It can be given 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 dosing 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 taking it.

A: 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.

You can inject your semaglutide dose just under the skin (subcutaneously) on your abdomen, upper arm, or thigh. Avoid injecting it into the same spot every time. Changing your injection site with each dose can help limit injection site reactions.

After you’ve selected and cleaned your injection site, you can remove the pen cap. Push the pen firmly against your skin, which will trigger the injection. You should hear a “click” and the yellow bar should start moving. Continue holding the pen here until the bar stops. Throw away 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.

A: 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
• Increased risk of thyroid C-cell tumors

A: Yes. Semaglutide can interact with diabetes medications, especially insulin and those that increase insulin release (such as sulfonylureas). This combination can increase the risk of your blood glucose 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.

A: 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?

A: 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 (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. Plus, it’s a controlled substance.

Qsymia: Phentermine is also available in combination with topiramate under the brand name Qsymia. Compared to phentermine alone, Qsymia can 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).

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.

Tirzepatide was approved by the FDA for the treatment of type 2 diabetes in 2022 under the brand name Mounjaro® and for chronic weight management in 2023 as Zepbound™. This makes it a relative newcomer in the fast-moving industry compared to semaglutide brand names like Ozempic®, Wegovy®, and Rybelsus®.

Tirzepatide works by combining the actions of two hormones involved in glucose regulation: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). By activating both GLP-1 and GIP receptors, tirzepatide helps lower blood sugar levels through multiple pathways, including increasing insulin secretion and reducing glucagon secretion from the pancreas, slowing gastric emptying, and enhancing feelings of fullness.

Recent studies have shown that tirzepatide provides greater reductions in body weight and improved glycemic control compared to other GLP-1 medications.

The most common adverse events associated with tirzepatide are gastrointestinal, including nausea, diarrhea, and vomiting. These side effects are usually temporary and tend to resolve over time as your body adjusts to the medication

In medical terms, titration refers to the process of adjusting the dosage of a medication based on an individual’s response to treatment. This involves starting with a low dose and gradually increasing it until the desired therapeutic effect is achieved while minimizing side effects. Titration is common in managing conditions such as diabetes, hypertension, and psychiatric disorders, where finding the optimal dosage is crucial for effective treatment.

Dose titration is recommended with tirzepatide to improve tolerability. This means giving your body time to adjust to the medication. Starting with a lower dose allows healthcare providers to assess the individual’s response and minimize the risk of adverse effects.

For tirzepatide, titration typically involves increasing the dose every four weeks, based on your prescriber’s discretion, until you reach the optimal dosage for your body. This could range from 5 mg to 15 mg, depending on how your body reacts. Most patients find their optimal dosage at 5 mg or 7.5 mg.

Semaglutide and tirzepatide are FDA-approved injectable medications for chronic weight management and can also lower the risk of serious cardiovascular problems in certain people with heart disease. 

You’ll usually start with a low dose that’s slowly increased until you reach the target dose.

Both can cause side effects such as nausea, vomiting, and diarrhea, especially within the first several months of treatment. It can also interact withdiabetes medications, such as insulin, and medications that you take by mouth.

Talk to your healthcare team to learn more about semaglutide and tirzepatide for weight loss.

They can recommend the best chronic weight management option for you.

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