Q&A: How Specific GLP-1s Impact Different Patient Populations | ASHP Midyear

Glucagon-like peptide-1 (GLP-1) receptor agonists have proved to be the definitive standard of practice for the treatment of patients living with obesity and type 2 diabetes (T2D). However, with several variations of the medication entering the prescription drug market, it’s important for pharmacists to understand their patients’ needs and know how different GLP-1s will impact specific patient outcomes.

“Everyone is talking about tirzepatide and semaglutide, which have revolutionized the management of T2D and obesity. Tirzepatide offers very high efficacy for weight loss (more than semaglutide, based on recent evidence) most likely due to its dual mechanism, while semaglutide has established itself as a leader with its proven cardiovascular benefits,” said Jennifer Clements, PharmD, BCACP, BC-ADM, BCPS, CDCES, FADCES, FCCP.

Tirzepatide (Mounjaro) injection | image credit: MKPhoto / stock.adobe.com

In a session presented at the American Society of Health-System Pharmacists (ASHP) 2024 Midyear Clinical Meeting, Clements discussed GLP-1 treatment for patients with obesity and T2D. From the differences between tirzepatide and semaglutide to increasing supply and demand for GLP-1s in general, learn about these ground-breaking medications, how they’re showing efficacy in patients of multiple disease states, and what pharmacists need to know to ensure safe dispensing of these products.

Drug Topics: Can you describe the current landscape of GLP-1 and GIP/GLP-1 medications that are available to patients?

Jennifer Clements: It has been groundbreaking and impactful to clinical practice for GLP-1 receptor agonists and GIP/GLP-1 receptor agonists to be available for the management of T2D, obesity, and now other chronic conditions. These single/dual receptor agonists promote regulation of glucose levels, reduction in appetite, and weight loss.

Semaglutide is the most commonly prescribed GLP-1 receptor agonist and is available under brand-name Ozempic (for T2D), Wegovy (for obesity), and Rybelsus (oral formulation for T2D). For Ozempic and Wegovy, semaglutide is a subcutaneous, once-weekly injection whereas Rybelsus has once-daily administration.

There are other GLP-1 receptor agonists, such as liraglutide, dulaglutide, and exenatide. Recently, liraglutide was approved as a generic medication for the management of T2D. It is important to remember the each GLP-1 receptor agonist may have different indications and dosing regimens, but there may be similarities with contraindication and adverse events. For example, semaglutide has an indication for cardiovascular risk reduction as Ozempic and Wegovy; in addition, dulaglutide—as Trulicity—has a similar indication due to benefit seen in cardiovascular outcome trials. However, exenatide extended-release (or Bydureon) does not have the risk reduction in cardiovascular events in its indication. For similarities, these long-acting GLP-1 receptor agonists cannot be used in individuals with personal or family history of medullary thyroid carcinoma due to evidence from animal studies.

Currently, there is one GLP-1/GIP-1 receptor agonist—tirzepatide; its brand-name product is Mounjaro for T2D and Zepbound for obesity. It is a once-weekly subcutaneous injection. The dosing is similar for both products. Recently, Zepbound was approved to treat moderate-to-severe obstructive sleep apnea for individuals living with obesity. As a dual receptor agonist, tirzepatide enhances insulin secretion from pancreatic beta-cells, suppresses glucagon from pancreatic alpha cell, slows gastric emptying, and therefore, reduces weight.

Everyone is talking about tirzepatide and semaglutide which have revolutionized the management of T2D and obesity. Tirzepatide offers very high efficacy for weight loss (more than semaglutide based on recent evidence) most likely due to its dual mechanism, while semaglutide has established itself as a leader with its proven cardiovascular benefits. Both medications provide patients with effective tools to address glycemic and weight management, improving quality of life and reducing long-term health risks. The choice between these therapies depends on individual’s needs, preferences, tolerability, response, and insurance coverage.

Drug Topics: What are the benefits of tirzepatide and semaglutide specifically for patients with obesity and T2D?

Jennifer Clements: Both tirzepatide and semaglutide have shown significant benefits for people living with obesity and T2D.

Tirzepatide has been shown to lead to substantial weight loss. In the SURMOUNT-1 trial, participants with obesity and prediabetes experienced an average weight reduction of up to 23% over three years. The same trial revealed that tirzepatide significantly reduced the risk of progression to T2D, as approximately 1.3% of participants on tirzepatide developed T2D, compared to 13.3% in the placebo group. In the SURMOUNT-2 trial, tirzepatide resulted in a 15% weight reduction in people living with obesity and T2D over 72 weeks. There are other benefits of tirzepatide beyond diabetes and obesity, as evidence has been published on heart failure with preserved ejection fraction and obstructive sleep apnea. Overall, tirzepatide improves insulin sensitivity and enhances glucose-dependent insulin secretion, helping to maintain better glycemic control; it can also slow gastric emptying and promote satiety to reduce weight.

Semaglutide has also been effective in promoting weight loss. Studies have shown that it can help promote significant weight loss, which is crucial for managing obesity and T2D. Semaglutide can regulate glucose levels by mimicking the action of the GLP-1 hormone, which promotes insulin release and reduces glucagon levels. Semaglutide has been associated with cardiovascular risk reduction, which is particularly beneficial for people living with T2D and obesity who are at higher risk for cardiovascular disease. In addition, there are other benefit of semaglutide beyond diabetes obesity, as evidence has been published on heart failure with preserved ejection fraction and osteoarthritis.

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