How Peptides for Weight Loss Work

Peptide medications may make you feel fuller to help with weight loss. They were initially designed for type 2 diabetes treatment.

Your body naturally produces incretin hormones, such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide receptor (GIP).

These hormones perform several functions, such as:

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

In people with type 2 diabetes, incretin levels are absent or lower than usual. Peptide medications mimic incretin hormones. 

GLP-1 receptor agonists, such as Wegovy (semaglutide), bind to cell receptors where the natural hormones bind. They help lower blood sugar and A1C levels in people with type 2 diabetes. They also decrease appetite and food intake, and support weight loss.

The Food and Drug Administration (FDA) has approved three peptide medications, or incretin mimetics, specifically for weight loss. These include Wegovy, Saxenda (liraglutide), and Zepbound (tirzepatide).

Semaglutide

Wegovy, Ozempic, and Rybelsus are brand names for semaglutide, a GLP-1 receptor agonist approved for weight loss in people with obesity. Wegovy slows the movement of food through your stomach, helping you feel full with less food and decreasing the urge to eat.

You start with a small dose of 0.25 milligrams weekly for the first month. The dose increases over time.

In a 2021 study, people with obesity lost an average of 33 pounds over about 16 months. Wegovy is also approved to lower the risk of major cardiovascular events in adults with heart disease who are overweight or have obesity.

Liraglutide

Saxenda and Victoza are brand names for liraglutide, a GLP-1 receptor agonist approved for weight loss. It requires daily injection.

With Saxenda, you start by injecting 0.6 milligrams daily under your skin. You increase the dose weekly until you reach 3 milligrams daily. 

In a year-long 2015 study, people without diabetes who took Saxenda lost an average of 18 pounds. About 60% lost at least 5% of their starting weight. One in three lost over 10%, compared with those on placebo.

Tirzepatide

In late 2023, the FDA approved tirzepatide, a weekly injection for weight loss in adults, sold under the brand names Zepbound and Mounjaro.

Zepbound is the first GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist marketed specifically for weight management. It controls appetite, slows digestion, and increases fullness.

When starting Zepbound, you will inject 2.5 milligrams weekly for the first month, then increase the dose to 5-15 milligrams weekly.

In a 2022 study by Zepbound's manufacturer Eli Lilly, people without diabetes who took 5 milligrams weekly lost 15% of their body weight over 16 months. Those on 15 milligrams weekly lost 21%.

People on Zepbound for 20 months lost 25% of their starting weight, compared to 10% for those on a placebo.

Peptide medications require a prescription from a doctor.

Adults can use Wegovy, Saxenda, or Zepbound if their body mass index (BMI) is 30 or higher, or if their BMI is 27 or higher with a weight-related health condition like high cholesterol or type 2 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. The FDA also expanded Saxenda's approval to include adolescents 12 and older with a BMI of 30 or higher and who weigh more than 132 pounds. 

Peptide medications seem effective for weight loss, especially when you use them with a balanced diet and regular exercise. Both Wegovy and Saxenda work as GLP-1 receptor agonists, but some evidence suggests that Wegovy may be more effective.

In a 2022 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%.
• About 70% of people on Wegovy lost at least 10% of their body weight, compared with 30% on Saxenda.
• Wegovy caused more stomach discomfort than Saxenda, but more people stopped taking Saxenda than Wegovy.

Saxenda may be less effective because it does not last as long in the body and needs to be taken daily. More research is needed, but Zepbound might be more effective for weight loss. People using Zepbound lost nearly 21% of their body weight and kept much of it off.

It's important to remember that these medications do not work the same for everyone. Diet, exercise, and health history play a role in their effectiveness.

Peptide medications can cause some side effects, especially when you first start them, such as:

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

Seek medical attention right away if you develop any severe side effects or are diagnosed with a serious medical condition.

Always report any new or worsening symptoms to a doctor, even if they are not listed here:

• Allergic reactions
• Depression
• Gallbladder problems
• Hypoglycemia (low blood sugar)
• Kidney disease
• Pancreatitis (inflammation of the pancreas)

Zepbound and Wegovy may also make birth control pills less effective. Peptide medications for weight loss are also not considered safe during pregnancy. Notify a doctor right away if you are taking Zepbound, Wegovy, or similar medications and find out you are pregnant.

Peptide medications for weight loss are designed for long-term use. They are effective at helping you maintain your weight loss while you continue taking them.

You could regain some or all of the weight you lost if you discontinue the medication. These medications are most effective when combined with a balanced diet and regular exercise, which may help you maintain weight. 

They can also be expensive and may not be covered by insurance. Saxenda costs about $1,350 for a 30-day supply, Wegovy costs $1,350 for a 28-day supply, and Zepbound costs $1,060 for a 28-day supply.

Most manufacturers offer co-pay savings cards and assistance programs to help you pay less.

Demand for weight loss medications has increased and created a shortage. Some pharmacies have made custom or compounded versions of semaglutide.

Unlike regular prescription drugs, compounded medications are unique formulations. A doctor may prescribe a compounded medication when the regular prescription medication, dose, or form you need is not available. 

Compounded versions of semaglutide come with safety concerns. They have not undergone rigorous testing like FDA-approved medications.

Make sure it's safe if you are interested in compounded semaglutide. Discuss the possible benefits and risks with a doctor before buying.

Avoid buying semaglutide online without a prescription. It may be counterfeit or contain the wrong ingredients.