December 5, 2022
GLP-1 Agonists for Weight Loss: An Evidence-Based Review

GLP-1 Agonists for Weight Loss: An Evidence-Based Review

Weight loss can be challenging for many people, even when they follow a healthy diet and exercise regimen. Because of this, some people may look for other methods to support weight loss, such as medication.

One popular medication that the Food and Drug Administration (FDA) has recently approved is semaglutide, which is better known by the brand name Wegovy.

This medication is a GLP-1 agonist that is designed to help reduce hunger and food intake, thus potentially supporting weight loss.

Although it is FDA-approved, you may wonder whether it’s right for you and whether there are any side effects you should know about.

This article tells you all you need to know about GLP-1 agonists such as Wegovy and whether they can help with weight loss.

Wegovy (semaglutide) is a drug that the FDA approved for use as a weight loss medication in 2021.

It’s a GLP-1 agonist, which means it mimics a naturally produced hormone called glucagon-like peptide 1 (GLP-1). This hormone is partly responsible for regulating hunger.

Wegovy is an injection that you receive once per week. For the first 16 weeks, you receive smaller doses, starting at 0.25 milligrams (mg) and working up to 1.7 mg. You then continue with a weekly maintenance dose of 2.5 mg for as long as it supports weight loss.

Healthcare professionals may prescribe it for people who have an initial body mass index (BMI) of 30 or higher or those who have a BMI of 27 or higher and at least one “weight-related” health condition, such as type 2 diabetes, high blood pressure, or dyslipidemia.

Doctors commonly prescribe this medication alongside other weight loss interventions, such as a low calorie diet and an exercise regimen.

Wegovy (semaglutide) works by acting as a GLP-1 agonist.

GLP-1 is a hormone that your body naturally produces. It has many roles but is best known for its role in regulating hunger and food intake.

The release of this hormone can help delay emptying of the stomach, so food stays in your stomach longer and you feel full longer. It also helps suppress another hormone, called glucagon. This can prevent you from feeling hungry.

GLP-1 agonists act by binding to GLP-1 receptors, resulting in the same effects.

Originally, GLP-1 agonist drugs were used to treat type 2 diabetes. These drugs increase the release of insulin, a hormone your pancreas produces. This helps remove excess sugar from your blood and thus lowers your blood sugar levels.

Over time, researchers noticed that GLP-1 agonists seemed to decrease appetite and promote weight loss. Thus, they began studying the use of GLP-1 agonists as weight loss medications.

It’s important to keep in mind that Wegovy was specifically made and approved as a weight loss drug. Ozempic, another GLP-1 agonist, is meant for the treatment of type 2 diabetes.

Wegovy has been shown to support significant weight loss in many studies, but it’s important to consider that most of them were funded by Wegovy’s manufacturer. That means there’s a potential for bias and conflict of interest to influence the study results.

One recent review found that taking 2.4 mg of Wegovy once per week led to reductions in weight across multiple studies and was more effective than a placebo.

For a 68-week randomized, double-blind clinical trial (known as STEP 4), researchers recruited 902 participants to take either Wegovy (2.4 mg weekly) or a placebo. Both groups received the same diet and exercise prescriptions.

For the first 20 weeks, all participants received weekly Wegovy injections. At 20 weeks, participants were split into a treatment (Wegovy) group and a placebo group.

By the end of the study, the treatment group saw a 7.9% decrease in body weight, while the placebo group saw a 6.9% increase in body weight.

The treatment group also had significant reductions in waist circumference, hemoglobin A1C (HbA1c) levels, systolic blood pressure, total cholesterol, and triglycerides.

However, the researchers who conducted STEP 4 received funding from Novo Nordisk — the manufacturer of Wegovy — and other pharmaceutical companies.

Another 2021 double-blind study — also funded by Novo Nordisk — involving 1,961 participants with obesity found an average weight loss of 14.9% in the Wegovy group (2.4 mg weekly) compared with only 2.4% in the placebo group. Both groups followed the same diet and exercise recommendations.

A 2022 study compared Wegovy (semaglutide) with liraglutide (Saxenda), another GLP-1 agonist.

The study’s 338 participants were split into 4 groups: Wegovy (2.4 mg weekly), liraglutide (3 mg daily), and 2 placebo groups. All groups also made changes to their diet and exercise habits.

After 68 weeks, the Wegovy group had an average weight loss of 15.8%, while the liraglutide group had an average weight loss of 6.4%. The authors suspected that Wegovy could better decrease food cravings and hunger, leading to less food intake.

However, keep in mind that the researchers conducting this study also received funding from Novo Nordisk.

Ultimately, the effectiveness of Wegovy (semaglutide) when paired with diet and exercise led the FDA to approve the drug in 2021.

However, Wegovy may not be accessible to everyone because of its high cost. Without insurance, it may cost more than $1,500 per month.

Though GLP-1 agonists such as Wegovy may support weight loss, it’s important to be aware of the possible side effects:

  • nausea
  • vomiting
  • stomach pain
  • headache
  • fatigue
  • dizziness
  • constipation or diarrhea
  • heartburn, indigestion, or GERD (gastroesophageal reflux disease)
  • low blood sugar in people with type 2 diabetes
  • bloating, belching, and flatulence
  • mood changes
  • drug interactions

Less common but more severe side effects include:

  • allergic reaction (anaphylaxis)
  • acute pancreatitis
  • acute choleliathiasis (gallstones)
  • acute kidney injury
  • diabetic retinopathy in people with type 2 diabetes
  • changes in heart rate
  • suicidal behavior or ideation
  • risk of thyroid C-cell tumors

In one study, nearly half of the people taking semaglutide reported gastrointestinal side effects.

Ultimately, it’s important to discuss any concerns you have with a healthcare professional to make sure the product is right for you.

If you’re looking to lose weight without using medication, there are many strategies you can try, such as:

  • Making more homemade meals: Cutting back on ultra-processed foods and takeout can reduce your calorie consumption.
  • Eating more fiber and protein: Fiber and protein can help increase fullness, since foods high in these substances take longer to digest.
  • Limiting added sugars: Calories from added sugars — especially from sugary beverages — can add up quickly. You may want to opt for water or low calorie beverages more often.
  • Increasing your physical activity: Moving your body helps you burn more calories and can improve other aspects of your physical and mental well-being.
  • Getting enough sleep: Lack of sleep can contribute to less nutritious food choices and a decrease in physical activity. Plus, sleep helps you recover and feel your best, both physically and emotionally.
  • Working with a registered dietitian: Registered dietitians are nutrition specialists and can work with you to identify positive, health-promoting food choices to support weight loss.
  • Working with other health professionals: Weight may be only one piece of the puzzle of your health. Working closely with a trained professional (such as a physical therapist, social worker, psychologist, or endocrinologist, depending on your needs) can help ensure that you’re getting well-rounded care.

Here are some questions people often ask about taking GLP-1 agonists for weight loss.

Which GLP-1 agonist is for weight loss?

Wegovy and Saxenda are the only GLP-1 agonists that are approved as weight loss drugs.

Do GLP-1 agonists suppress appetite?

GLP-1 agonists such as Wegovy have been shown to suppress appetite, which may lead to decreased food intake.

Who should not take GLP-1 agonists?

Those who should not take GLP-1 agonists include people who are pregnant, nursing, or planning to become pregnant; have a history of thyroid cancer or pancreatitis; are allergic or sensitive to semaglutide; or have multiple endocrine neoplasia (MEN) syndrome type 2.

Weight loss medications are not generally recommended for people with past or active eating disorders.

Further, people who are taking other GLP-1 agonists should not take Wegovy. This medication may have other potential drug interactions, which are not well known. It’s important to thoroughly discuss any possible interactions with the prescribing healthcare professional.

Wegovy (semaglutide) is a weight loss drug that the FDA approved in 2021. It acts as a GLP-1 agonist, which helps promote feelings of fullness by delaying stomach emptying and decreasing levels of hunger hormones.

Numerous studies have found that Wegovy is an effective weight loss drug, especially when combined with a reduced calorie diet and an exercise regimen.

However, most studies that have reported positive results have been funded by Novo Nordisk, the manufacturer of Wegovy. That means there is room for potential bias and conflict of interest in the research.

Plus, Wegovy isn’t for everyone and can result in undesirable side effects. Therefore, it’s important to weigh the pros and cons with a healthcare professional.

If you’re more interested in weight loss strategies that do not involve medication, you might consider trying a variety of healthy habits that can help support meaningful weight loss.

You may want to try eating more fiber and protein, eating fewer ultra-processed foods, increasing your physical activity, looking for healthy ways to manage your stress levels, or making an effort to get enough sleep.