Differences Among Popular GLP-1 Receptor Agonists for Type 2 Diabetes

A class of medications known as GLP-1 receptor agonists has revolutionized the treatment of type 2 diabetes and obesity. These drugs mimic the action of glucagon-like peptide-1 (GLP-1), a hormone that stimulates insulin secretion and inhibits glucagon release, helping to regulate blood sugar levels and promote weight loss. In this podcast, we’ll talk about the differences among some of the most well-known GLP-1 receptor agonists for type 2 diabetes.

Ozempic (Semaglutide)

• Form: Injectable
• Dosing Frequency: Once weekly
• Uses: Primarily for type 2 diabetes (lower blood sugar and A1c); also approved for reducing the risk of major cardiovascular events like heart attack and stroke in adults with type 2 diabetes and known heart disease.

Keep in mind, Wegovy (semaglutide) is a higher-dose version that’s approved for weight loss. When you start taking Wegovy or Ozempic, you’ll begin with a low dosage. Your prescriber will increase your dosage every four weeks until you reach the target amount. However, the specific dosage you inject will differ depending on the medication. The maximum dose for Ozempic is 2mg weekly, while the target dose for Wegovy is 2.4mg weekly.

Rybelsus (Semaglutide)

• Form: Oral tablet
• Dosing Frequency: Once daily
• Uses: Lower blood sugar and A1c in people with type 2 diabetes.

Rybelsus shares the same active ingredient as the injectable medications Ozempic and Wegovy. Ozempic is also approved for Type 2 diabetes, while Wegovy is approved specifically for weight loss.

Rybelsus is available in three different strengths: 3 mg, 7 mg, and 14 mg. Similar to Ozempic, the dose is slowly increased every 4 weeks. 

Good to know: It’s important to take Rybelsus first thing in the morning with 4 oz of water. After taking it, you should wait at least 30 minutes before eating, drinking, or taking other medications. Failing to do so may reduce its effectiveness.

Currently, Rybelsus is undergoing clinical trials to evaluate its effectiveness for weight loss. The trials involve higher doses than those approved for diabetes treatment. Results indicate that a 50 mg dose of oral semaglutide (Rybelsus) achieves weight loss comparable to Wegovy. 

Trulicity (Dulaglutide)

• Form: Injectable
• Dosing Frequency: Once weekly
• Uses: Type 2 diabetes; and like Ozempic, it’s also approved for reducing the risk of major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease.

Like Ozempic and Rybelsus, you will start at a low dose to help reduce side effects. Your healthcare provider will then gradually increase the dose, balancing the management of side effects with the benefits of blood sugar control. The maximum dose for Trulicity is 4.5mg weekly.

Victoza (Liraglutide)

• Form: Injectable
• Dosing Frequency: Once daily
• Uses: Type 2 diabetes; also approved to reduce the risk of major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease.

Victoza is one of three GLP-1 agonists approved for treating Type 2 diabetes in children aged 10 and older. The other options are Trulicity (dulaglutide) and Bydureon BCise (exenatide). More on this later. Ozempic, however, is only approved for use in adults.

Saxenda and Victoza are both injectable medications containing liraglutide, but they are approved for different uses. Saxenda is FDA-approved for chronic weight management in people 12 and older, while Victoza is approved for treating Type 2 diabetes in people 10 and older. Victoza also helps lower the risk of major adverse cardiovascular events in adults with diabetes and heart disease.

Both medications are injected once a day, starting with a low dose that is gradually increased over time. The target dose for Saxenda is 3 mg once daily, whereas the maximum dose for Victoza is 1.8 mg once daily.

Byetta (Exenatide)

• Form: Injectable
• Dosing Frequency: Twice daily
• Uses: Type 2 diabetes.
• Additional Benefits: It has a shorter duration of action than other GLP-1 agonists, which may be preferable for some patients.

Byetta, approved in 2005, was the first GLP-1 medication of its kind for diabetes. Its active ingredient, exenatide, is a synthetic version of a substance found in Gila monster saliva.

The recommended starting dose for Byetta is 5 mcg twice daily, administered within 60 minutes before your morning and evening meals. After one month, your healthcare provider may increase the dose to 10 mcg twice daily. Starting at a lower dose helps reduce stomach-related side effects.

Bydureon BCise (Exenatide Extended-Release)

• Form: Injectable
• Dosing Frequency: Once weekly
• Uses: Type 2 diabetes.
• Additional Benefits: Extended-release formulation provides a more convenient dosing schedule compared to Byetta.

Unlike Byetta, Bydureon BCise has a fixed dose of 2 mg administered once weekly, on the same day each week. It can be taken at any time of day, with or without food.

Mounjaro (Tirzepatide)

• Form: Injectable
• Dosing Frequency: Once weekly
• Uses: Type 2 diabetes.
• Additional Benefits: Dual action as it targets both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors, potentially offering enhanced efficacy in blood sugar control.

Mounjaro is not approved for weight loss; however, its active ingredient, tirzepatide, is approved for weight loss under the brand name Zepbound.

Typically, Mounjaro’s starting dose is 2.5 mg once weekly for four weeks. By week 5, the dosage is often increased to 5 mg once weekly for another four weeks. Following week 9, if necessary for better blood sugar management, the dosage can be escalated to 7.5 mg weekly.

It’s important not to increase Mounjaro doses by more than 2.5 mg every four weeks. The maximum recommended dosage is 15 mg once weekly.

Unlike Ozempic, Trulicity, or Victoza, Mounjaro is currently not approved for any heart-related uses. However, an ongoing clinical trial is assessing its effectiveness in reducing major adverse cardiovascular events in people with Type 2 diabetes. The study is anticipated to conclude in October 2024.

Key Differences and Considerations

The right GLP-1 agonist for you will likely come down to a few key factors like age, treatment goals, and underlying health conditions. Personal preferences like dosage frequency will also come into play.

1. Dosing Frequency:
   • Once weekly: Ozempic, Trulicity, Bydureon BCise, Mounjaro.
   • Once daily: Rybelsus (oral), Victoza, Saxenda.
   • Twice daily: Byetta.
2. Administration Form:
   • Injectable: All except Rybelsus (oral).
   • Oral: Rybelsus.
3. Indications:
   • Type 2 Diabetes: All medications.
4. Cardiovascular Benefits:
   • Proven cardiovascular benefits: Ozempic, Trulicity, Victoza.
5. Pediatric Use:
   • Approved for children: Victoza (for children 10 years and older).

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