What Role Do Peptides Play in Weight Loss?

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Medically reviewed by Kashif J. Piracha, MDMedically reviewed by Kashif J. Piracha, MD

Proteins are made up of smaller units called amino acids, which link together like the beads of a bracelet. A string of about 50 amino acids is called a peptide. Your body produces many types of peptides. Insulin, which regulates blood sugar, is one example of a peptide hormone. 

Scientists have also created peptides in laboratories as treatments for various health conditions. Some of these peptide medications include glucagon-like peptide-1 (GLP-1) receptor agonists. They also include a combination of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, or GLP-1/GIP.

Many of these GLP-1 and GLP-1/GIP receptor agonists were initially developed to treat type 2 diabetes. However, an unexpected side effect was noticed: people taking these medications began losing weight. This surprising discovery opened new possibilities for using peptide medications for weight loss. But how exactly do they work?

How Peptides Work

Your body naturally produces the hormones GLP-1 and GIP, known as incretin hormones. These hormones have several functions. For example, they:

  • Signal the pancreas to release more insulin after eating
  • Help to reduce glucose (sugar) production in the liver
  • Slow down how quickly food leaves the stomach
  • Increase the feeling of fullness after meals
  • Reduce appetite and food cravings

In people with type 2 diabetes, incretin levels are absent or lower than they should be.  Peptide medications, like GLP-1 and GLP-1/GIP receptor agonists, are manufactured substances that act like incretin hormones, which is why they’re also called incretin mimetics. For example, a GLP-1 receptor agonist, like Wegovy (semaglutide), acts like the GLP-1 hormone in your body. 

These medications attach to specific sites on certain cells, called receptors, where the natural hormones normally would. In doing so, they help lower blood sugar and A1C levels in people with type 2 diabetes. They also lead to a lower appetite, which reduces food intake and encourages weight loss.

Types of Peptides for Weight Loss

Currently, three peptide medications or incretin mimetics have received approval by the U.S. Food and Drug Administration (FDA) specifically for weight loss. These include Wegovy, Saxenda, and Zepbound.

Wegovy

Wegovy (semaglutide) is a GLP-1 receptor agonist that’s FDA-approved specifically for weight loss in certain people living with obesity. Wegovy is a once-weekly medication, and you don’t need a diabetes diagnosis to be prescribed this medication.

Here are some qualifications:

  • Adults can use Wegovy if their body mass index (BMI) is 30 or higher. You might also qualify for the medication if your BMI is 27 or higher and you have a weight-related health condition, like hypertension (high blood pressure), high cholesterol, or diabetes.
  • Adolescents 12 years and older whose weight is at or above the 95th percentile for their age and sex can also qualify for Wegovy. This means their BMI is higher than 95% of other teenagers of the same age and sex.

When you start Wegovy, you begin with a small dose. You inject 0.25 milligrams (mg) of the medication under your skin once a week for the first month. Then, your prescriber will slowly increase your monthly dose until you reach the appropriate dose to maintain your weight loss.

Wegovy slows food moving through your stomach, makes you feel full with less food, and reduces your urge to eat. In a study, people with obesity but without diabetes who used 2.4 mg of Wegovy along with lifestyle changes lost 33 pounds on average in about 16 months. Many study participants noticed weight loss as early as four weeks after starting the medication.

In addition to weight loss, Wegovy is approved to reduce the risk of major adverse cardiovascular events (MACE), such as heart attack or stroke, in adults with heart disease who are overweight or living with obesity.

Saxenda

Saxenda (liraglutide) is another GLP-1 receptor agonist approved for weight loss, similar to Wegovy. However, a key difference between the two medications is that Saxenda requires a daily injection.

Like Wegovy, Saxenda is approved for use in adults with a BMI of 30 or higher. The medication is also an option for adults with a BMI of 27 or higher who have at least one weight-related health condition, such as type 2 diabetes, hypertension, or high cholesterol. The FDA also expanded Saxenda’s approval to include adolescents aged 12 and older with a BMI of 30 or higher and weighing more than 132 pounds. 

Saxenda treatment begins with a low dose and gradually increases over time. You’ll start by injecting 0.6 mg daily under your skin. Your healthcare provider will then guide you to slowly raise the amount each week until you reach the full dose of 3 mg daily. 

In a year-long study funded by Saxenda’s manufacturer, Novo Nordisk, people without diabetes who took Saxenda lost an average of 18 pounds. In the same study, about 60% of people taking Saxenda lost at least 5% of their starting weight, while one in three people lost over 10% of their body weight. This resulted in significantly more weight loss than was seen with the participants who received the placebo medication.

Zepbound

In late 2023, the FDA approved Zepbound (tirzepatide), a weekly injection, for weight loss in adults. Unlike other weight-loss injections, Zepbound is the first GLP-1/GIP receptor agonist marketed specifically for weight management. It works by targeting both GLP-1 and GIP receptors. This dual action helps control appetite, slow digestion, and increase feelings of fullness.

Zepbound, like Wegovy and Saxenda, is authorized for use in adults with a BMI of 30 or higher. The medication is also an option for adults with a BMI of 27 or higher who have at least one weight-related health condition. Unlike other weight loss injections, however, Zepbound is not approved for use in adolescents or children.

When starting Zepbound, you’ll inject 2.5 mg under your skin once a week for the first month. Your prescriber will then increase it to 5 mg weekly. Depending on how you respond to the medication, the dose may be adjusted to 10 mg or 15 mg weekly. 

Based on a study sponsored by Zepbound’s manufacturer, Eli Lilly, people without diabetes taking 5 mg of Zepbound weekly lost an average of 15% of their body weight over 16 months. On the other hand, those on the highest dose (15 mg weekly) lost about 21% of their body weight. For example, someone weighing 200 pounds at the start might lose about 30 pounds on the lower dose or 42 pounds on the high dose.

In a follow-up study, people who continued taking Zepbound lost another 6% of their body weight on average, while those who switched to a placebo gained back 14%. Overall, people who took Zepbound for the full length of the study (about 20 months) lost about 25% of their starting weight, compared to 10% for those who switched to a placebo.

Effectiveness and Benefits of Taking Peptides

Peptide medications seem effective for weight loss, especially when used with a healthy diet and exercise. While both Wegovy and Saxenda work as GLP-1 receptor agonists, studies suggest that Wegovy may be more effective.

In a study lasting nearly 16 months, researchers found that:

  • People taking Wegovy lost about 16% of their body weight, while those taking Saxenda lost about 6% of their body weight.
  • About 70% of people on Wegovy lost at least 10% of their body weight, compared to 30% of people on Saxenda.

The same study found that Wegovy caused more stomach discomfort than Saxenda. However, more people stopped taking Saxenda than Wegovy.

The researchers believe there are a few reasons for this. Saxenda doesn’t last as long in the body, so people might feel hungry again faster if they miss a dose. This might make some people think Saxenda isn’t working well for them. Also, Saxenda needs to be taken daily, which may be less convenient than a weekly injection. 

Although comparison study results are not yet available, current research suggests that Zepbound might be one of the most effective peptide medications for weight loss. For example, people using Zepbound not only lost a significant amount of weight (nearly 21%) but also managed to keep much of it off while taking the medication.

Still, it’s important to remember that these medications don’t work the same for everyone. Your diet, exercise routine, health history, and body’s reaction to the medication all play a role in their effectiveness.

Risks and Side Effects

While peptide medications can be effective for weight loss, like other medications, they can cause some side effects. The most common ones for peptides include:

  • Nausea and vomiting
  • Diarrhea or constipation
  • Stomach pain or indigestion
  • Headache
  • Fatigue
  • Injection site reactions
  • Dizziness
  • Facial changes, such as loss of fullness in the face

Stomach-related side effects are usually worse when you first start the medication or when your dose is increased. They often get better over time.

Serious side effects, while rare, may include:

If you experience any of these serious side effects, seek medical attention. Always report any new or worsening symptoms to your healthcare provider, even if they’re not listed here.

Zepbound and Wegovy may also make birth control pills less effective. Peptide medications for weight loss are not considered safe during pregnancy. If you’re taking Zepbound, Wegovy, or similar medications and find out you’re pregnant, notify your healthcare provider immediately.

Things To Consider

Peptide medications for weight loss are designed for long-term use. They’re effective at helping you maintain your weight loss while you continue taking them. However, if you discontinue the medication, you could regain some or all of the weight you’ve lost.

These medications aren’t meant to work alone. They’re most effective when combined with nutritious eating and regular exercise. These good habits may also help you maintain your weight if you stop taking the medication. 

These medications can also be expensive and may not be covered by insurance plans. For example, Saxenda costs about $1,350 for a 30-day supply, Wegovy is $1,350 for a 28-day supply, and Zepbound is $1,060 for a 28-day supply.  However, these are the manufacturer list prices, meaning the pharmacy’s actual retail cost might be higher.

Still, most manufacturers offer copay savings cards and assistance programs to help you pay less.

Alternatives

Demand for weight loss medications has increased recently, creating a shortage. As a result, some pharmacies started making custom-made versions—or compounded versions—of semaglutide. You might even see ads for compounded semaglutide marketed as a more affordable option to the brand-name medication.

Unlike regular prescription drugs, compounded medications are unique formulations made by specialized pharmacies. A healthcare provider may prescribe a compounded medication when the regular prescription medication, dose, or form you need isn’t available.

However, compounded versions of semaglutide come with safety concerns because they haven’t undergone rigorous testing like FDA-approved medications would.

For example, the FDA reported that some people making compounded weight loss medications are using “salt forms” of semaglutide, which are not the same as the regular semaglutide used in approved drugs like Wegovy. The salt forms haven’t been tested or approved, so their safety and effectiveness are unknown.

If you’re interested in compounded semaglutide, make sure it’s safe. Discuss the potential benefits and risks with your healthcare provider before buying. Additionally, avoid buying semaglutide online without a prescription. According to the FDA, these medications may be counterfeit and contain the wrong ingredients.

A Quick Review

Peptide medications for weight loss, such as Wegovy, Saxenda, and Zepbound, mimic natural hormones in your body to reduce appetite and control cravings. These medications seem effective when combined with diet and exercise. However, they can cause side effects, mainly stomach-related problems.

Because they are designed for long-term use, side effects often subside, and people taking these medications notice significant weight loss.

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