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Which GLP-1 Agonist Is Best for Weight Loss? A Comprehensive Guide

Compare and find the Best GLP-1 Agonist for your weight loss goal

Glucagon-like peptide-1 receptor agonists have become increasingly popular medications for managing type 2 diabetes and promoting weight loss. These drugs mimic the effects of the natural GLP-1 hormone, which helps reduce blood pressure, regulate blood sugar, reduce appetite, and promote feelings of fullness.

With numerous options available in the market, choosing the most suitable option for weight loss can be challenging.

  • Discover the differences between GLP-1 drugs like Ozempic, Wegovy, and Trulicity. Learn about side effects, scientific comparisons, and how they work for weight loss.GLP-1 agonists help regulate blood sugar, reduce appetite, and promote weight loss.
  • Semaglutide (Wegovy, Ozempic, Rybelsus) is one of the most effective options, with Wegovy leading in weight loss results.
  • Tirzepatide (Zepbound, Mounjaro) shows the highest weight loss efficacy, with studies reporting up to 21% body weight reduction.
  • Liraglutide (Saxenda, Victoza) is effective but requires daily injections and results in modest weight loss.
  • Dulaglutide (Trulicity) is primarily for diabetes but may aid in weight management.
  • GLP-1 agonists vary in administration schedules (weekly vs. daily) and dosage methods (oral vs. injectable).
  • LookMeds' compounded versions of GLP-1 agonists offer a cost-effective and accessible alternative.

Understanding GLP-1 Agonists

GLP-1 agonists are a class of diabetes and weight loss medications that mimic the action of the glucagon-like peptide-1 hormone in the body. This hormone plays a crucial role in regulating blood sugar levels and appetite. These agonists work through several mechanisms:

Stimulating insulin release: GLP-1 agonists stimulate the release of insulin from the pancreas when blood sugar levels are high, helping lower these levels.

Reducing glucose production: These medications reduce the production of glucose in the liver, further contributing to lower blood sugar levels.

Slowing gastric emptying: These hormones slow down the movement of food from the stomach to the small intestine, which can lead to increased feelings of fullness and reduced appetite.

Promoting satiety: By acting on receptors in the brain, agonists can increase satiety signals, helping individuals feel full and eat less.

FDA-Approved GLP-1 Agonists As Weight Loss Drugs

Several GLP-1 agonists have been approved by the U.S. Food and Drug Administration (FDA) for weight loss. These medications have demonstrated efficacy in clinical trials for bringing noticeable changes in body mass index (BMI) and are available in various formulations, including injections and oral tablets.

Semaglutide (Wegovy, Ozempic, Rybelsus)

Semaglutide is a GLP-1 receptor agonist available in three different brand names: Ozempic, Rybelsus, and Wegovy. Ozempic is a once-weekly injection, and Rybelsus is a once-daily oral tablet. 

Both are approved to improve glycemic control in adults with type 2 diabetes and to reduce the risk of major adverse cardiovascular events (MACE) in adults with both type 2 diabetes and established cardiovascular disease.

Wegovy is a higher-dose, once-weekly injection approved specifically for weight loss in adults and adolescents.

Efficacy: Clinical trials have demonstrated that semaglutide is highly effective for weight loss. In one trial, adults receiving Wegovy experienced an average weight loss of nearly 15% of their initial body weight.

Adolescents in clinical trials also experienced an average weight loss of almost 15% of their initial body weight. Semaglutide has also been shown to reduce the risk of MACE in adults with heart disease and a larger body size.

Administration: Wegovy and Ozempic are administered as a once-weekly subcutaneous injection. Rybelsus is taken orally once daily.

Considerations: Semaglutide is not recommended for people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Common side effects include nausea, vomiting, diarrhea, and constipation.

Liraglutide (Saxenda, Victoza)

Liraglutide is available under two brand names: Victoza and Saxenda. Victoza is a once-daily injection approved to improve glycemic control in adults and children 10 years and older with type 2 diabetes. It’s also approved to reduce the risk of MACE in adults with type 2 diabetes and established cardiovascular disease.

Saxenda is a higher-dose, once-daily injection approved for chronic weight management in adults and pediatric patients 12 years and older who meet certain criteria.

Efficacy: In a clinical trial, adults using Saxenda experienced an average weight loss of 8% of their starting body weight. Adolescents in a separate trial experienced an average weight loss of a little over 2.5% of their starting body weight.

Administration: Both Victoza and Saxenda are administered as a once-daily subcutaneous injection.

Considerations: Liraglutide is not recommended for people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Common side effects include nausea, vomiting, diarrhea, and constipation.

Dulaglutide (Trulicity)

Dulaglutide, sold under the brand name Trulicity, is a once-weekly GLP-1 receptor agonist injection approved for managing type 2 diabetes. While it’s not specifically for weight loss, it can cause modest reductions in body weight, making it a potential option for individuals seeking glycemic control with some weight management benefits.

Efficacy: Clinical trials have demonstrated that dulaglutide can result in a mean weight loss of approximately 3-5% of body weight, depending on the dosage and patient population. While it is less effective for weight loss than semaglutide or tirzepatide, it may benefit patients primarily managing diabetes.

Administration: Trulicity is administered as a once-weekly subcutaneous injection. It is available in different dose strengths, with higher doses showing better weight loss outcomes.

Considerations: Dulaglutide is not recommended for individuals with a history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Common side effects include nausea, vomiting, diarrhea, and abdominal pain.

Tirzepatide (Zepbound, Mounjaro)

Tirzepatide is a GIP and GLP-1 receptor agonist available under two brand names: Mounjaro and Zepbound. Mounjaro is a once-weekly injection approved to improve glycemic control in adults with type 2 diabetes.

Zepbound is a once-weekly injection approved for chronic weight management in overweight or obese adults with at least one weight-related comorbidity.

Efficacy: Clinical trials have demonstrated that tirzepatide is highly effective for weight loss. In one trial, people receiving Zepbound lost nearly 21% of their starting body weight over 72 weeks. Tirzepatide has also been shown to be more effective than semaglutide for both glucose control and weight loss.

Administration: Both Mounjaro and Zepbound are administered as a once-weekly subcutaneous injection.

Considerations: Tirzepatide is relatively new to the market, so long-term safety data are still emerging. Common side effects include nausea, vomiting, diarrhea, and constipation.

Comparing GLP-1 Agonists for Weight Loss

While all FDA-approved GLP-1 agonists can promote weight loss, some may be more effective than others. A meta-analysis presented at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting found that tirzepatide at 15 mg was the most efficacious GLP-1 agonist for obesity management in patients without diabetes.

Tirzepatide: In the meta-analysis, tirzepatide 15 mg was given a 98% chance of being the most effective treatment. Tirzepatide 10 mg was ranked at 89%, while semaglutide 2.4 mg and tirzepatide 5 mg were both ranked at 65%.

Semaglutide: Semaglutide 2.4 mg was the second most effective agent for weight management, inducing a mean change in body weight of -13.61%. Lower doses of semaglutide and oral semaglutide were found to be less effective.

Liraglutide: Liraglutide was the least effective examined in the meta-analysis, with a 3 mg dose inducing a -4.79% change in body weight.

Another meta-analysis of 76 randomized trials found that tirzepatide was the most effective approved agent for both glycemic control and weight loss, with semaglutide ranking second.

The most effective agent for weight loss overall was an investigational combination of semaglutide and the amylin analog cagrilintide.

Find Your Rx at LookMeds

Why LookMeds’ Compounded Version is a Viable Option

Given the proven effectiveness of tirzepatide and semaglutide for weight loss, access to these medications can be a challenge due to high demand and limited availability. LookMeds offers a compounded version of these GLP-1 agonists, providing patients with a more accessible and cost-effective alternative without compromising efficacy.

Compounded medications are custom-prepared by licensed pharmacies to match the specific needs of patients, allowing for tailored dosing that may not be available with standard prescriptions.

LookMeds’ compounded tirzepatide and semaglutide are formulated under strict quality standards, ensuring they maintain the same active ingredients as their FDA-approved counterparts.

For individuals who are unable to obtain brand-name GLP-1 agonists due to shortages or insurance restrictions, LookMeds’ compounded solutions offer a reliable and effective way to continue their weight loss journey with clinically supported treatments.

Factors to Consider When Choosing a GLP-1 Medication

When selecting a GLP-1 agonist for weight loss, consider the following factors:

Efficacy: As discussed above, some have demonstrated greater efficacy for weight loss than others.

Route of administration: These agonists are available in both injectable and oral forms. Consider personal preferences and tolerability when choosing a route of administration.

Dosing frequency: Some agonists are administered once daily, while others are administered once weekly. Consider your lifestyle and ability to adhere to the prescribed dosing schedule.

Side effects: All GLP-1 agonists can cause side effects, such as nausea, vomiting, diarrhea, and constipation. Discuss potential side effects with your healthcare provider and consider your personal risk factors.

Cost and insurance coverage: These medications can be expensive, and insurance coverage may vary. Check with your insurance provider to determine coverage and out-of-pocket costs.

Underlying health conditions: Certain agonists may be more appropriate for people with specific underlying health conditions, such as heart disease or kidney disease. Discuss your health history with your healthcare provider to determine the best option for you.

Potential Risks and Side Effects

Like all medications, GLP-1 agonists carry potential risks and side effects. It is important to be aware of these risks and discuss them with your healthcare provider before starting treatment.

Common side effects: The most common side effects of GLP-1 agonists are gastrointestinal issues such as nausea, vomiting, diarrhea, constipation, and abdominal pain. These side effects are typically mild and temporary, but they can bother some people.

Serious side effects: In rare cases, these drugs can cause more serious side effects, such as pancreatitis, gallbladder problems, kidney problems, and allergic reactions. Seek medical attention immediately if you experience any severe or persistent side effects.

Mental health concerns: Some reports have linked GLP-1 agonists to an increased risk of depression and suicidal ideation. If you have a history of mental health problems, discuss the potential risks with your healthcare provider before starting treatment.

Muscle loss: It can lead to loss of both fat and muscle mass. This can be particularly concerning for older adults, as muscle loss is associated with an increased risk of falls, fractures, and mortality. Incorporating resistance training and ensuring adequate protein intake can help mitigate muscle loss.

Learn more about semaglutide and tirzepatide’s potential risks.

The Role of GLP-1 Agonists in Type 2 Diabetes Management

GLP-1 agonists were initially developed to treat type 2 diabetes, not weight loss. Despite this added benefit, they remain an important diabetes medication. In addition to promoting weight loss, GLP-1 agonists offer several benefits for people with type 2 diabetes:

Improved glycemic control: GLP-1 agonists help lower blood sugar levels by stimulating insulin release, reducing glucose production, and slowing gastric emptying.

Reduced risk of cardiovascular events: Some agonists have been shown to reduce the risk of major adverse cardiovascular events (MACE) in people with type 2 diabetes and established cardiovascular disease.

Potential kidney benefits: Some agonists may have kidney-related benefits, such as slowing the progression of kidney disease.

Emerging GLP-1 Agonists and Combination Therapies

The field of GLP-1 receptor agonists is rapidly evolving, with new medications and combination therapies in development. These emerging treatments aim to improve efficacy, reduce side effects, and address additional metabolic conditions.

Combination therapies: Researchers are exploring the potential of combining these with other medications, such as amylin analogs and GIP receptor agonists, to enhance weight loss and improve metabolic health.

Triple agonists: Some companies are developing triple agonists that target GLP-1, glucagon, and the pancreatic polypeptide receptors. These medications may offer even greater benefits for weight loss and metabolic control.

Bottom Line

GLP-1 agonists can be a valuable tool for weight loss and type 2 diabetes management. However, they are not a magic solution and should be used in conjunction with lifestyle modifications.

Tirzepatide appears to be the most effective agonist currently available for weight loss, but other options, such as semaglutide and liraglutide, can also be effective. Factors such as route of administration, dosing frequency, side effects, cost, and underlying health conditions should be considered when choosing a GLP-1 agonist.

It’s important to work with a healthcare professional to determine the best option for your individual needs and to develop a comprehensive plan that includes diet, exercise, and behavioral changes.

Ultimately, the best GLP-1 agonist for weight loss is the one that’s most effective, safe, and tolerable for the individual. With careful consideration and guidance from a healthcare professional, GLP-1 agonists can be a powerful tool for achieving sustainable weight loss and improving overall health.

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