Semaglutide vs. Other GLP-1 Receptor Agonists: A Comprehensive Comparison

GLP-1 receptor agonists, or glucagon-like peptide-1 receptor agonists, were initially developed to help individuals with type 2 diabetes better control their blood sugar levels. However, they have also shown remarkable promise in the realm of weight management.

There are many different types of GLP-1 agonists available on the market, and researchers are still learning about all the potential uses and benefits of this medication.

As with any class of drugs, not all GLP-1 receptor agonists are created equal. Understanding the differences between various options is crucial. Those differences can impact their effectiveness, tolerability, and suitability for individual patients.

In this article, we will explore the different GLP-1 weight loss options available on the market and determine what sets Semaglutide apart.

What are GLP-1 receptor agonists?

GLP-1 is a naturally occurring hormone in the small intestine. When we eat, GLP-1 is released into the bloodstream, and it triggers several critical responses.

GLP-1 receptor agonists mechanism of action mimics the naturally occurring GLP-1 in the body, which results in improved blood sugar control. As research continues, it is becoming more and more apparent that their benefits extend beyond glucose regulation.

Studies have shown that GLP-1 receptor agonists are effective for preventing or managing obesity.

How GLP-1 receptor agonists aid in weight loss?

GLP-1 and GLP-1 receptor agonists mechanism of action triggers a series of responses that can aid in both glucose regulation and weight loss:

• Insulin release: GLP-1 stimulates the pancreas to release insulin. Insulin is the hormone responsible for helping glucose (sugar) in the bloodstream enter cells, where it can be used for energy or stored.
• Inhibition of glucagon: GLP-1 inhibits the release of glucagon, another hormone produced by the pancreas. Glucagon’s role is to raise blood sugar levels by prompting the liver to release stored glucose. By inhibiting glucagon, GLP-1 helps prevent excess glucose release.
• Slowing gastric emptying: GLP-1 also slows down the rate at which the stomach empties its contents into the small intestine. This effect leads to a feeling of fullness and helps control post-meal spikes in blood sugar levels.

This way, Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) help you lose weight by taming your hunger, slowing down digestion, and making you feel fuller after meals.

Overview of GLP-1 Receptor Agonists

The major GLP-1 receptor agonists available on the market currently are:

• Dulaglutide (Trulicity)
• Exenatide extended release (Bydureon BCise)
• Exenatide (Byetta)
• Semaglutide (Ozempic, Rybelsus)
• Liraglutide (Victoza, Saxenda)
• Lixisenatide (Adlyxin)

What is Dulaglutide (Trulicity) and its mechanism of action

Dulaglutide, sold as Trulicity, is an injectable GLP-1 receptor agonist medication designed for the treatment of type 2 diabetes. It gained popularity for its once-weekly dosing schedule, something that most other GLP-1 receptor agonists now match.

The Dulaglutide mechanism of action is the same as any other GLP-1 receptor agonists mechanism of action mimicking the naturally occurring GLP-1 hormone, limiting blood sugar levels, preventing excessive glucose production, and promoting satiety.

Trulicty makes a claim that 94% of adults say it was easy to use thanks to their preloaded pens. They also claim that more than half of users reached an A1C under 7%.

The recommended dose varies but is often started at 0.75 mg weekly and may be increased based on individual response.

While it is only FDA approved for the treatment of diabetes, studies have shown it has promise in promoting weight loss, with people losing up to 10 pounds.

What is Exenatide extended release (Bydureon BCise)?

Like other GLP-1 receptor agonists, Exenatide extended release, sold as Bydureon BCise, works by mimicking the action of the natural hormone GLP-1. It activates GLP-1 receptors, leading to increased insulin release from pancreatic beta cells in response to elevated blood sugar levels, making it an excellent treatment for type 2 diabetes.

This Exenatide injection is typically 2 mg injected subcutaneously once per week — preferably on the same day. It comes in a pre-filled, single-use autoinjector pen, making it convenient for patients.

The extended-release formulation of Exenatide provided in Bydureon BCise sets it apart. The medication is released gradually over time, providing a sustained effect.

As with many of the options on this list, it is not FDA-approved for use as a weight loss medication. While it does promote weight loss, results are not as significant as with other options.

What is Exenatide (Byetta) and does it work?

Unlike some of the other GLP-1 receptor agonists,  this Exenatide injection is administered twice daily. It is meant to be taken within one hour before the morning and evening meals.

Byetta is effective in improving blood sugar control, particularly after meals, and can help lower HbA1c levels effectively. While the twice daily injections may be a deterrent for many patients, but it is a particularly suitable option for individuals who experience significant post-meal glucose spikes.

Like many GLP-1 receptor agonists, Byetta has been associated with weight loss or weight maintenance in some individuals.

A 2016 review of studies showed that this Exenatide injection led to a more significant reduction of body weight and body mass index (BMI). Despite the promise, it is not approved for weight loss specifically.

What is Semaglutide (Ozempic, Rybelsus) and does it work?

Semaglutide is a widely popular GLP-1 receptor agonist used for the management of type 2 diabetes and obesity. It’s available in multiple formulations, with Ozempic and Rybelsus being some of the most well-known.

A 2018 study showed Ozempic was more effective than Dulaglutide while a 2019 study showed it to be more effective than liraglutide in weight loss.

Ozempic is a once weekly injection, while Rybelsus is a once daily pill — one of the few oral formulations.

Semaglutide’s dual benefits of improving blood sugar control and promoting weight loss, along with its availability in both injectable and oral formulations, make it a popular and versatile choice for those looking to lose weight.

What is Liraglutide (Victoza, Saxenda) and its mechanism of action?

Liraglutide, marketed under the brand names Victoza for diabetes management and Saxenda for weight management, is a versatile GLP-1 receptor agonist with a distinct focus on weight loss. Both are administered daily.

Like the relationship between Ozempic and Wegovy, Saxenda is simply a higher dosage of Victoza. This higher dose is specifically designed to enhance its weight loss effects.

Liraglutide has a strong emphasis on weight management, but some studies show that Semaglutide, as both Ozempic and Rybelsus, is more effective.

What is Lixisenatide (Adlyxin)?

Lixisenatide, marketed under the brand name Adlyxin, is another GLP-1 receptor agonist used for the management of type 2 diabetes. According to one study, “Lixisenatide has a high affinity for the GLP-1 receptor, up to four times greater than human GLP-1.”

Lixisenatide is a once daily subcutaneous injection with dosing based on individual needs. While not approved for weight loss, it has shown promise in promoting weight loss. It also shows potential cardiovascular benefits. Adlyxin has since been discontinued.

Comparative Analysis: Semaglutide vs. Other GLP-1 Receptor Agonists

Each of the GLP-1 receptor agonists on this list has unique advantages and considerations. But, ultimately, the choice of which GLP-1 receptor agonist to use should be based on a patient’s specific medical needs, preferences, and discussions with a healthcare provider.

Cost can also be a major consideration. If you do not have type 2 diabetes and the medication is not FDA-approved for weight loss, your insurance will not cover the costs, and you’ll be paying out of pocket for these medications.

GLP-1 receptor agonists list

Here’s a comparison table of the various GLP-1 receptor agonists discussed in previous sections:

GLP-1 agonist side effects to consider

All GLP-1 receptor agonists have similar side effects. You may experience:

• Nausea: nausea is a common side effect with many GLP-1 receptor agonists, but its severity can vary between individuals.
• Gastrointestinal distress: diarrhea and abdominal pain can occur but are usually mild.
• Loss of appetite: due to the mechanisms of action, loss of appetite is also a common side effect. 
  
• Injection site reactions: for the subcutaneous injections, some may experience mild injection site reactions.

GLP-1 agonist benefits to consider

For those who are at greater risk of cardiovascular issues, some of the GLP-1 receptor agonists have shown cardiovascular benefits or a neutral cardiovascular profile. These include Semaglutide, Liraglutide, and Lixisenatide.

What is the Best GLP-1 for Weight Loss?

While GLP-1 receptor agonists were developed to treat type 2 diabetes, many have demonstrated significant weight loss or weight maintenance effects. If you’re looking for the best GLP-1 for weight loss, the answer isn’t going to be black and white.

But, if you’re looking for a cost-effective and easy-to-use option, semaglutide can’t be beat.  The effectiveness and safety of this weight loss medications can vary between patients, which is why it is important to discuss with a healthcare provider.  You can connect with a licensed physician at Heally to get a semaglutide prescription today!