ASHP Midyear: Expert Discusses GLP-1 Medications and Incretin Mimetics for Diabetes Care

Incretin mimetics encompass a class of medications that enhance insulin secretion and suppress glucagon release. DPP-4 inhibitors are a type of incretin mimetic with moderate glucose-lowering effects and neutral cardiovascular and renal outcomes. GLP-1 receptor agonists and GLP-1/GIP receptor agonists (like tirzepatide) offer greater glucose control and significant weight loss. Tirzepatide, in particular, demonstrates high efficacy for both glucose lowering and weight loss, but requires careful monitoring for gastrointestinal side effects and potential drug interactions. 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, discusses the pharmacists role in diabetes care.

GLP-1, Diabetes, Type 2 Diabetes | Image Credit: © neirfy | stock.adobe.com

Pharmacy Times: How do incretin mimetics differ from GLP-1 receptor agonists?

Jennifer Clements: Incretin mimetics is considered the umbrella term for different therapeutic classes, such as dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. From my experience, incretin mimetics as terminology is declining as we are often referring to the specific class of medications. DPP-4 inhibitors continue to be used in practice since they are an oral formulation that is prescribed as a once daily regimen. However, the glucose lowering efficacy is intermediate which means it is typically an average A_1c reduction of 0.8%, as it targets postprandial glucose levels. However, if a DPP-4 inhibitor is prescribed then a GLP-1 or GLP-1/GIP receptor agonist cannot be prescribed because it would be seen as therapeutic duplication given mechanism of action. DPP-4 inhibitors work in a glucose dependent manner to increase insulin secretion from pancreatic beta cells and suppress glucagon from pancreatic alpha cells. To be complete but not too detailed, DPP-4 inhibitors do differ among the GLP-1/ or GLP-1/GIP receptor agonists in other ways, such as weight loss effects as the receptor agonist slow gastric emptying and promote satiety in the brain. In addition, DPP-4 inhibitors have been found to have a neutral effect on major adverse cardiovascular events as well as heart failure. More specifically, saxagliptin has a potential risk of increasing the risk of heart failure. DPP-4 inhibitors have been shown to have a neutral effect on the progression of chronic kidney disease even though there are recommended dose adjustments for sitagliptin, saxagliptin, and alogliptin.

Pharmacy Times: What are some of the benefits and risks of incretin mimetics for type 2 diabetes?

Clements: GLP-1 receptor agonists and GLP-1/GIP receptor agonist are often referred to as single or dual receptor agonist, respectively. Since I have already talked about the single receptor agonist, I would like to discuss the dual receptor agonist—also known as tirzepatide (Zepbound, Mounjaro; Eli Lilly). It has a very high efficacy for lowering glucose levels with no risk of hypoglycemia when used as monotherapy. In addition, it has a very high efficacy for promoting weight loss. There is ongoing evidence evaluating its effect on major adverse cardiovascular events as well as heart failure and kidney outcomes. There is no dose adjustment for kidney function; however, it is recommended that kidney function be monitored when initiating or escalating the doses particularly in those with kidney impairment who may be reporting severe adverse gastrointestinal reactions due to the risk of dehydration and volume depletion. Tirzepatide has impact on gastric emptying which is greatest after the initial dose and the first dose of each escalation; the impact will decrease over the next 4 weeks since it is a once weekly medication. Due to the impact on drug absorption, orally administered medications could be impacted, including oral contraceptives. It is important to change oral contraceptives to non-oral contraceptives or add the barrier method when initiating tirzepatide and following each dose escalation for 4 weeks. Like GLP-1 receptor agonists, the same mitigation strategies to lower the risk of gastrointestinal side effects can be promoted with tirzepatide.

Pharmacy Times: What is the role of the pharmacist for helping patients manage GLP-1s and incretin mimetics as therapy?

Clements: A pharmacist has a role in ensuring appropriate initiation as well as titration for each agent. Pharmacists can follow up on tolerability with agents after each dose escalation and provide education on mitigation strategies to reduce adverse events such as nausea, vomiting, diarrhea, and/or constipation. A pharmacist has the knowledge to review proper storage, preparation, and administration of these products particularly with demo devices. Pharmacists stay up to date on the evidence and clinical practice guidelines. Therefore, pharmacists have a role in educating individuals on the benefits of these specific agents as well as potential risks. Overall, I would say that pharmacists can customize the person-centered plan based on clinical evidence including clinical practice guidelines when updated and have proactive strategies to overcome challenges and barriers and promoting evidence-based practices and justifying beneficial therapy for people living with type 2 diabetes and/or obesity.

Pharmacy Times: Is there anything else you would like to add?

Clements: At this time, I would add that there is a lot of emerging evidence with single or dual receptor agonists, specifically with semaglutide (Ozempic, Wegovy; Novo Nordisk) and tirzepatide. Some of this evidence revolves more around the brand-name products indicated for obesity management. Semaglutide, as Wegovy, has recent evidence among individuals who are living with obesity or are overweight and showing improvements for outcomes associated with osteoarthritis and heart failure with preserved ejection fraction. Additional evidence is emerging with tirzepatide, as Zepbound, which is indicated for obesity. As of December 20, its indication was expanded beyond obesity and now includes management of moderate-severe obstructive sleep apnea. It is important as pharmacists to stay aware of the emerging evidence and utilize resources to remain up-to-date on the data and aware of changes with accessibility for patients.