How Do The Different GLP-1 Receptor Agonists Compare

Glucagon-like peptide-1 (GLP-1) receptor agonists continue to increase in popularity as more and more people experience their effectiveness in treating type 2 diabetes mellitus and aiding in weight loss. The three most popular GLP-1 receptor agonists for weight management are semaglutide, tirzepatide, and liraglutide. You’re probably already familiar with these names, however, few people understand their differences. We’ll discuss each medication individually and then compare them head-to-head to help you consider if either one may be right for you.

What is Semaglutide?

Semaglutide, which is known by the brand names of Ozempic® and Wegovy®, is a glucagon-like peptide 1 (GLP-1) receptor agonist originally developed to treat type 2 diabetes. Overtime, semaglutide also demonstrated significant success with weight loss. 

How does it help you lose weight exactly? Well, GLP-1 receptor agonists like semaglutide mimic the functions of the GLP-1 hormone made in your gut in response to food intake. These include triggering insulin release and blocking glucagon secretion. So, when you start taking a GLP-1 medication, it increases the effects of your body’s naturally occuring GLP-1 hormone.

The GLP-1 receptor agonist then helps lower blood glucose by sending it to organs and tissues to be used for energy. In addition, GLP-1 slows gastric emptying, increases fullness, reduces appetite, and leads to decreased overall calorie intake. By binding to GLP-1 receptors, GLP-1 receptor agonists increase the activity of GLP-1, improving glucose control and increasing weight loss. 

Advantages and disadvantages of semaglutide for weight loss

Advantages

For weight loss, semaglutide is available in a higher dose. Many clinical trials have already shown impressive weight loss results. The STEP trial compared the use of semaglutide 2.4 mg weekly to placebo over two years, and semaglutide demonstrated a 15.2% weight loss, as compared to 2.6% with no medication.

One of the advantages of using semaglutide for weight loss is its convenient weekly dosing. However, the formulation of semaglutide approved for weight loss is an injection, which can be a downside for some people.

Disadvantages

Side effects

Semaglutide can cause notable side effects, most commonly gastrointestinal upset (like nausea and vomiting) and hypoglycemia (low blood sugar), which can often be eased by dietary adjustments. More serious side effects, such as pancreatitis and thyroid cancers, are rare. Semaglutide is not a magic weight loss remedy; it should be used in conjunction with a healthy diet, regular physical exercise, and other lifestyle modifications.

What is Tirzepatide?

Tirzepatide, which is known by the brand names of Mounjaro® and Zepbound®, is another medication designed to treat type 2 diabetes but shown to have significant weight loss effects as well. 

While they work similarly, tirzepatide works on two main pathways instead of one. Tirzepatide is a dual agonist; it is a GLP-1 receptor agonist (like semaglutide) and also a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist.

GIP is another neuroendocrine hormone involved in regulating blood sugar levels and insulin secretion. By targeting both the GIP and GLP-1 receptors, tirzepatide delivers not only a clinically significant reduction in blood glucose but also notable weight reduction through its synergistic effects on weight loss, decrease in fat mass, and reduction in appetite. 

Advantages and disadvantages of tirzepatide for weight loss

Advantages

Tirzepatide has been shown to be very effective for weight loss. Within a randomized controlled trial, at a maximum dosage of 15 mg, tirzepatide demonstrated a 20.9% weight reduction over 3.1% in patients taking no medication. The increased effectiveness of tirzepatide is likely related to its dual action on both the GIP and GLP-1 receptors for additive impact. Tirzepatide is less studied for weight loss, with ongoing research to further determine its long-term safety and efficacy.

Disadvantages

Side effects

Tirzepatide is also given in a once-weekly injection, like semaglutide. The side effects of tirzepatide are similar to those of semaglutide, the most common ones being gastrointestinal upset and hypoglycemia, but evidence suggests the intensity of side effects may be more severe with tirzepatide.

Cost

Tirzepatide is often more expensive than semaglutide, although it may lead to cost savings in the long run.

What is Liraglutide?

Liraglutide, known by the brand names of Victoza® and Saxenda®, is most similar to semaglutide. It is a GLP-1 receptor agonist that is approved for the treatment of diabetes (Victoza®) and obesity (Saxenda®). Its mechanism of action is the same as semaglutide, as it works on the GLP-1 receptor to increase the activity of GLP-1 for appetite reduction, increased satiety, overall lower calorie intake, and glucose control.

Advantages and disadvantages of liraglutide for weight loss

Advantages

Liraglutide is not a brand new drug; it was approved for use in the United States in 2010, as compared with 2017 for semaglutide and 2022 for tirzepatide. Liraglutide does lead to statistically significant weight loss: 5.7%, versus 1.6% with no medication. It also offers cardiovascular disease risk reduction, as do many of the other GLP-1 receptor agonists.

Disadvantages

Dose frequency & effectiveness

Liraglutide is given once-daily, as opposed to once weekly, which may be a disadvantage for some people. Liraglutide is less effective than both semaglutide and tirzepatide in lowering blood glucose and in weight loss success. For its lower efficacy, liraglutide is still associated with similar, possibly more severe, gastrointestinal side effects. 

Head-to-head comparison of the 3

After understanding each medication individually, here’s how semaglutide, tirzepatide, and liraglutide compare.

• Semaglutide and liraglutide act as an agonist on GLP-1 receptors only, whereas tirzepatide acts as a dual agonist on both GLP-1 and GIP receptors.

• Both semaglutide and tirzepatide for weight loss are given as once-weekly injections. Liraglutide is given as a once-daily injection.

• Semaglutide for weight loss offers 2 dosages: 1.7 mg and 2.4 mg. Liraglutide for weight loss starts at 0.6 mg and increases to 1.2 mg, 1.8 mg, 2.4 mg, and 3 mg. Tirzepatide is available in dosages of 2.5 mg, 5 mg, 10 mg, and 15 mg. Additional dosing options may better allow you to find a dose that is both effective and tolerable, with manageable side effects.

• The weight loss success is lowest in liraglutide. Semaglutide provides much more weight loss results, and weight loss is the highest with tirzepatide.

• Some evidence suggests that liraglutide causes the most side effects, leading to patients stopping the medication, although other evidence suggests that the rate of adverse effects depends on specific dosages between semaglutide and liraglutide. The side effects of semaglutide and tirzepatide are comparable.

• Tirzepatide tends to be more expensive than semaglutide and liraglutide.

Semaglutide vs. Tirzepatide vs. Liraglutide: How Should You Choose?

If you’re wondering if using semaglutide, tirzepatide, or liraglutide for weight loss is right for you, discuss the risks and benefits of each with your healthcare professional. Considering your weight loss goals, current glycemic control, other medical history, the medication availability, and any cost differences are all important to make the best decision for your overall health. 

Regardless of which medication you choose, remember that any medication for weight loss should be used in combination with a healthy diet, regular physical exercise, good quality sleep, and stress management to help maximize long-term weight loss success.