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Peptides for weight loss: Which ones work best?

Peptides for weight loss: Which ones work best?

Some peptides help promote weight loss by helping to regulate blood sugar levels, metabolism, and appetite. These medications may cause side effects and people must have a prescription to take them.

Peptides are small chains of molecules called “amino acids,” which are the building blocks of proteins.

Some of the most common peptides for weight loss belong to a class of drugs called glucagon-like peptide 1 (GLP-1) receptor agonists. These medications mimic the action of the natural hormone GLP-1, which the gut releases after eating.

This article asks whether peptides really work for weight loss, discusses how they work, and considers the best peptides for weight loss. It also highlights the potential side effects and other safety aspects.

Recent evidence shows that GLP-1 receptor agonists can help people lose weight.

  • stimulating the release of the hormone insulin, which helps regulate blood sugar
  • delaying stomach emptying (gastric emptying)
  • increasing fullness (satiety)
  • reducing appetite
  • alleviating food cravings

The best peptides for weight loss

The best peptides for weight loss are those approved by the Food and Drug Administration (FDA). Examples include:

Semaglutide

As a 2024 review explains, semaglutide is a GLP-1 receptor agonist. There are three separate semaglutide brands:

  • Rybelsus
  • Ozempic
  • Wegovy

Of these, the only drug to receive FDA approval as a weight loss aid is Wegovy.

Wegovy injection is FDA approved as a long-term weight loss aid for the following individuals:

  • adults with obesity, alongside a reduced-calorie diet, and increased physical activity
  • adults with overweight, and at least one weight-related condition, such as:
    • hypertension
    • type 2 diabetes
    • dyslipidemia
  • children ages 12 years or above with a body mass index (BMI) at or above the 95th percentile for their age and sex

A 2021 study investigated the effectiveness of semaglutide as a weight loss aid in 1,961 people with overweight or obesity. Over 68 weeks, each participant received a once-weekly dose of either 2.4 milligrams (mg) of subcutaneous semaglutide or placebo, alongside lifestyle interventions.

Individuals in the semaglutide treatment group lost, on average, 14.9% of their body weight compared to baseline. Individuals in the placebo group lost, on average, just 2.4% of their body weight compared to baseline.

The researchers also compared the percentage of individuals in each group who achieved weight reductions of 5% or more. The table below summarises these findings:

% of weight reduction from baselineIndividuals taking semaglutideIndividuals taking placebo
5% or more86.4%31.5%
10% or more69.1%12.0%
15% or more50.5%4.9%
Liraglutide

Liraglutide is another type of GLP-1 receptor agonist. As a 2024 review explains, the FDA approved liraglutide in 2014 for the treatment of adult obesity, and studies have also shown the drug to be effective in children ages 12 to 18 years.

Liraglutide goes by the following brand names:

  • Saxenda
  • Victoza

It is approved for weight loss in:

  • adults with obesity
  • adults with overweight and at least one weight-related health condition

A 2017 review and meta-analysis of five randomized controlled trials (RCTs) investigated the safety and effectiveness of liraglutide for weight management. The review found that the number of individuals achieving a weight loss of 5% or 10% was significantly higher in the liraglutide group compared to the placebo group.

Tirzepatide

Tirzepatide activates GLP-1 receptors and glucose-dependent insulinotropic polypeptide (GIP), an intestinal hormone that plays a role in insulin secretion and lipid metabolism.

In 2023, the FDA approved a tirzepatide injection with the brand name Zepbound for weight loss in the following individuals alongside a reduced calorie diet and increased physical activity:

  • adults with obesity
  • adults with overweight and at least one weight-related condition

Zepbound is both a GLP-1 receptor agonist and a GIP receptor agonist, so it helps reduce appetite and food intake. It is a subcutaneous injection that a person administers once a week.

The recommended starting dose is 2.5 mg. After the first 4 weeks, a person can gradually increase the dosage in 2.5 mg increments over the course of 4 to 20 weeks until they reach their target weekly dosage of 5 mg, 10 mg, or 15 mg.

A 2024 study investigated the effect of once-weekly subcutaneous tirzepatide on weight loss management in adults with overweight or obesity. At 36 weeks, the 670 adults experienced an average weight reduction of 20.9%.

From this time point, researchers separated the participants into two groups: a treatment group and a control group. At 52 weeks, the group continuing tirzepatide experienced an additional 5.5% weight reduction, while the group who switched to the placebo regained 14% of their body weight.

Using versions of GLP-1 receptor agonists that are not FDA-approved can be unsafe. They could contain harmful ingredients and too much or too little of the active ingredient. They may not contain any of the active ingredients at all.

Side effects and safety

According to the NIDDK, peptides and other weight loss medications may sometimes cause side effects that outweigh the benefits of weight loss.

For this reason, people should only take weight loss medications to improve their health, never for cosmetic reasons alone.

The chart below shows the possible side effects of Wegovy, Saxenda, and Zepbound:

Side effectSemaglutide (Wegovy)Liraglutide (Saxenda)Tirzepatide (Zepbound)
nausea
diarrhea
vomiting
constipation
abdominal pain
indigestion
fatigue
headache
dizziness
distended abdomen
burping
flatulence
gastroenteritis
gastroesophageal reflux disease (GERD)
low blood sugar in people with type 2 diabetes
runny nose and sore throat
injection site reactions
increased lipase levels
fever
hypersensitivity reactions
hair loss
gastritis
urinary tract infection
Precautions

Before prescribing peptides for weight loss, doctors must consider certain precautions.

Peptides for weight loss may delay gastric emptying, which can reduce the effectiveness of oral medications.

The FDA cautions that both Wegovy and Zepbound may not be suitable for use during pregnancy, as these medications may harm the fetus. The FDA recommends that males and females of reproductive age discontinue using Wegovy at least 2 months before a planned pregnancy, as the drug can remain in the system for several weeks.

With Zepbound, the FDA recommends that females using oral contraceptives switch to a non-oral contraceptive method or add barrier contraception for 4 weeks after the initial Zepbound dose, and for 4 weeks after each dose increase.

Peptides for weight loss may also not be suitable for people with a personal or family history of certain conditions, including:

  • medullary thyroid cancer
  • multiple endocrine neoplasia type 2
  • hypersensitivity to the active ingredient, or any other ingredient in the medication

When to contact a doctor

A person should contact a doctor if they want to discuss issues with their weight or require advice on appropriate weight loss methods and treatments.

A person should also contact a doctor if they are taking a weight loss medication and begin to experience side effects.

Depending on the nature and severity of the side effects, the doctor may recommend adjusting the medication dosage or switching to an alternative medication or weight loss method. However, a person should not stop taking a medication unless their doctor advises them that it is safe to do so.

Summary

Some of the most common peptides for weight loss are glucagon-like peptide 1 (GLP-1) receptor agonists. They include semaglutide (Wegovy), liraglutide (Saxenda), and tirzepatide (Zepbound).

GLP-1 receptor agonists can increase satiety, reduce appetite, and regulate blood sugar levels — all of which may help with weight loss.

However, peptides for weight loss can cause side effects and drug interactions, and may not be suitable for everyone.

Anyone considering peptides for weight loss can talk with a doctor about the risks and potential benefits and for general weight loss advice.