ASHP Midyear: Expert Discusses the GLP-1 Landscape for Diabetes Care

The 2025 ADA Standards of Care in Diabetes outline 2 primary approaches for managing type 2 diabetes: risk reduction, which prioritizes medications with proven cardiovascular and/or kidney benefits for high-risk individuals; and glycemic control and weight control, which focuses on achieving and maintaining glycemic goals, particularly in those at lower cardiovascular risk. Metformin and combination therapies are often initial choices. High-efficacy agents like dulaglutide, semaglutide, and tirzepatide are recommended for significant weight loss, while considering factors like hypoglycemia risk and liver function. Pharmacy Times® interviews Jennifer Clements, PharmD, FCCP, FADCES, BCPS, CDCES, BCACP, BC-ADM, a clinical professor and the director of pharmacy education at the University of South Carolina, about glucagon-like peptide-1 receptors for diabetes treatment.

GLP-1, Ozempic, Wegovy, Semaglutide, Diabetes, Weight Loss | Image Credit: © Peter Togel | stock.adobe.com

Pharmacy Times: What are the current guideline recommendations for type 2 diabetes?

Jennifer Clements: Based on the American Diabetes Association (ADA) Standards of Care in Diabetes (2025), Section 9 provides recommendations for the use of glucose-lowering medications in the management of type 2 diabetes. Every individual with type 2 diabetes should be educated on healthy lifestyle behaviors, referred for diabetes self-management education and support, and have social determinants of health addressed at clinical visits. Regardless of intervention, it is important to avoid clinical inertia and, therefore, treatment should be reassessed and modified on a regular basis such as every 3 to 6 months. These standards provide 2 different approaches for therapy, depending on the individual’s goals. If an individual with type 2 diabetes is at high risk for cardiovascular and/or kidney disease, then medication therapy can be driven based on evidence. For example, those with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) should be considered candidates for either a glucagon-like peptide-1 (GLP-1) receptor agonist or SGLT2 inhibitor with proven cardiovascular benefit. The same recommendation is suggested for individuals with type 2 diabetes and at high risk of ASCVD. As another example, a SGLT2 inhibitor with proven benefit should be recommended to those with type 2 diabetes and current or prior symptoms of heart failure. Lastly those with type 2 diabetes and chronic kidney disease (specifically an eGFR less than 60 mL/min/1.73 m² or albuminuria) can have a SGLT2 inhibitor recommended if a maximum tolerated dose of an angiotensin-converting enzyme inhibitor or angiotensin receptor blockers is prescribed. If there is a contraindication or intolerance to an SGLT2 inhibitor, then a GLP-1 receptor agonist with proven kidney benefit can be recommended.

Pharmacy Times: How do different guideline recommendations approach the management of obesity?

Clements: As mentioned before, 2 different approaches for therapy, depending on the individual’s goals. In the previous question, individuals with type 2 diabetes may need cardiovascular and/or kidney risk reduction and therefore, medication therapy will be tailored and driven based on evidence from outcome trials. As a reminder, medications within a specific class are not all equal as the ADA Standards clearly state that agents with proven benefit should be recommended. This does differ if we look at the second goal among people with type 2 diabetes needs to achieve and maintain weight and/or glycemic goals. It is important to think of this goal related to those that have type 2 diabetes but may not be at high risk for cardiovascular and/or kidney disease. When we look at achieving and maintaining glycemic goals, metformin or combination therapy can be recommended. When starting metformin or combination therapy, it is important to lower the risk of hypoglycemia and avoid in individuals more prone to this safety outcome. Specifically, there are medications with very high efficacy for glucose-lowering effects, which include high-dose dulaglutide (Trulicity; Eli Lilly), semaglutide (Ozempic, Wegovy; Novo Nordisk), tirzepatide (Zepbound, Mounjaro; Eli Lilly), insulin, combination oral, and combination injectable therapy. There are some additional agents with high efficacy and would include liraglutide (Victoza, Saxenda; Novo Nordisk), exenatide, and lixisenatide as well as oral agents (metformin, pioglitazone, SGLT2 inhibitor, sulfonylurea). In most cases individuals with type 2 diabetes will also need weight management. Subcutaneous semaglutide and tirzepatide have very high efficacy for promoting weight loss in this patient population, followed by high efficacy with dulaglutide and liraglutide. Regarding weight loss, the ADA Standards do recommend that therapy should also be directed towards mitigating the risk of liver dysfunction, such as metabolic dysfunction associated with steatohepatitis. Weight loss is the primary intervention to further mitigate the risk of liver dysfunction and additional benefit can be gained with a GLP-1 receptor agonist, tirzepatide, pioglitazone, or the combination of these agents.

Pharmacy Times: What are some of the potential benefits and risks of GLP-1 receptor agonists for type 2 diabetes?

Clements: When evaluating the GLP-1 receptor agonists as a class, it is important to remember that the agents have high to very high efficacy for lowering glucose levels, depending on the specific agent. When used as monotherapy, there is a low risk of hypoglycemia. Depending on the specific agent, there is an intermediate to very high efficacy for weight loss. Specific GLP-1 receptor agonists have benefits for cardiovascular reduction, and this includes subcutaneous injections of dulaglutide, liraglutide, and semaglutide. The effect on heart failure and associated outcomes have been found to be neutral with this therapeutic class. As subcutaneous injections, dulaglutide, liraglutide, and semaglutide have been shown to be beneficial in renal endpoints from cardiovascular outcome trials driven by albuminuria outcomes. However, recent evidence with subcutaneous semaglutide has demonstrated benefit in the progression of chronic kidney disease. In terms of risks, animal studies have indicated that there is a dose dependent and treatment duration dependent risk of thyroid C cell tumors but the relevance for humans has not yet been determined. For ileus, the level of risk has not been established; however, there is recent guidance on discontinuation prior to surgical procedures for this class of medications. Acute pancreatitis has been reported; causality has not been established. Therefore, it is recommended that GLP-1 receptor agonists are not initiated in individuals at high risk for pancreatitis and should be discontinued if pancreatitis is suspected. GLP-1 receptor agonists are typically avoided in those at risk for biliary disease and it is important to do further evaluation if this is suspected after initiation. The most common adverse events, include gastrointestinal [adverse] effects—nausea, vomiting, constipation, or diarrhea. These adverse events typically occur at initiation and each dose escalation; however, there are mitigation strategies and include reducing meal portions, practicing mindful eating, decreasing the intake of fatty, spicy, greasy foods, and considering a slower titration than dosing listed in the package insert.