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Pharmacy Times
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Pharmacists should emphasize the importance of medication adherence and lifestyle changes.
In recent years, glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide (Ozempic, Wegovy; Novo Nordisk), liraglutide (Saxenda, Victoza; Novo Nordisk), and tirzepatide (Mounjaro, Zepbound; Eli Lilly and Company) have revolutionized the treatment of type 2 diabetes and obesity. Initially developed solely to improve glycemic control in patients with diabetes, these medications have gained widespread attention for their significant weight loss benefits. As a result, their popularity has surged, with many individuals seeking to use them as weight management tools, either for an off-label use or an approved indication.1,2
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This dual application has significantly increased demand, leading to nationwide shortages that underscore the growing reliance on GLP-1 receptor agonists as a key diabetes therapy and a cornerstone in combating the obesity epidemic.3 Pharmacists have been tasked with managing the distribution of GLP-1 receptor agonists amid shortages and counseling patients to ensure safety and effectiveness.
Sofiya Volynsky, PharmD, is manager of clinical education and program implementation at Rite Aid, overseeing Division 2, which includes Washington, Oregon, and Idaho. In this role, she supports field leaders and pharmacies to ensure effective training and implementation of clinical programs and initiative
GLP-1 receptor agonists mimic the incretin hormone GLP-1. This hormone is crucial in enhancing glucose-dependent insulin secretion while inhibiting glucagon release to help regulate blood glucose levels. Additionally, GLP-1 receptor agonists delay gastric emptying and act on GLP-1 receptors in the hypothalamus to influence appetite regulation, resulting in suppression. This appetite suppression often leads to reduced caloric intake and subsequent weight loss. The combination of glucose regulation and weight reduction makes these medications particularly valuable for managing obesity, especially in individuals with metabolic syndrome or diabetes.4
Although many GLP-1 receptor agonists are available, only a few are specifically approved by the FDA for weight management, which has helped relieve some product shortages. Clinical trials have consistently demonstrated the effectiveness of GLP-1 receptor agonists in promoting weight loss.5
Semaglutide is approved for chronic weight management and has shown positive results in clinical studies, with participants achieving an average weight loss of 15% to 17% over 68 weeks.6 The Semaglutide Treatment Effect in People with Obesity (STEP) trials highlighted significant weight reduction in patients without diabetes, with a 2.4-mg weekly dose leading to an average weight loss of 14.9% compared with placebo.7
Liraglutide is another agent approved for weight loss, demonstrating a 5% to 10% reduction in body weight during clinical trials. Although its effects are slightly less pronounced than semaglutide, liraglutide has proven effective, particularly when combined with lifestyle interventions such as diet and exercise. Other agents, such as dulaglutide (Trulicity; Eli Lilly and Company) and exenatide (Byetta; AstraZeneca), are not approved by the FDA for weight management but may support weight loss as a secondary benefit when used primarily for diabetes.
Pharmacists and other health care providers play a key role in emphasizing adherence to medication regimens and lifestyle modifications, as the combination maximizes the therapeutic potential of these treatments. GLP-1 receptor agonists are primarily recommended for adults who meet specific criteria, including the following2,5,7:
Despite their benefits, these medications are contraindicated in certain populations, including those with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.1 Careful patient selection is critical to ensure safety and effectiveness. GLP-1 receptor agonists are well tolerated but can cause adverse effects (AEs) ranging from mild to severe. Common AEs include gastrointestinal symptoms such as nausea, vomiting, diarrhea, constipation, and abdominal pain. Less common but more serious AEs include hypoglycemia and gallbladder issues such as gallstones or cholecystitis. Rarely, these medications may exacerbate kidney problems, trigger pancreatitis, or cause allergic reactions such as rash, itching, or swelling. GLP-1 receptor agonists also carry a boxed warning about the potential risk of medullary thyroid carcinoma.4 Pharmacists can recognize and help patients manage most AEs caused by GLP-1 receptor agonists.
As mentioned previously, the rising demand for GLP-1 receptor agonists has led to widespread shortages in pharmacies. One of the primary drivers of the shortage is the surge in off-label use for weight management. The shortage disproportionately affects patients with type 2 diabetes, the population for whom these medications were initially intended. Without consistent access, patients may face difficulties maintaining glycemic control, increasing their risk of complications such as cardiovascular events, kidney damage, and neuropathy.5 One of the ways pharmacists have dealt with shortages is by limiting patients to a 30-day supply rather than 90 days. However, this practice has unintended consequences as it can lower adherence, especially for those with transportation barriers.
The pharmaceutical supply chain has struggled to keep pace with this rapid increase in demand. Manufacturing GLP-1 receptor agonists is a complex process requiring specialized equipment and stringent quality controls. Scaling production takes time, and any disruptions, such as shortages of raw materials or logistical issues, exacerbate the problem. The shortage also raises economic and ethical concerns. As demand outstrips supply, some patients face inflated prices or resort to secondary markets, where the cost of these medications can be prohibitively high. Furthermore, the allocation of limited supplies often prioritizes newer prescriptions over existing ones, leaving long-term users without consistent access. These challenges highlight a need for equitable distribution practices to prioritize those with medical necessity.
Pharmaceutical companies are ramping up production, but it may take months or years to resolve the issue.3 Health care providers are encouraged to consider alternative therapies for patients affected by the shortage. For weight management, lifestyle interventions or other pharmacological options may be explored; for diabetes, alternative glucose-lowering medications may be necessary. Improved patient education is also vital to managing expectations and ensuring adherence to available treatments.
GLP-1 receptor agonists have become a transformative class of medications. Initially designed for managing type 2 diabetes, they are now widely embraced for weight loss. However, their rising popularity for weight management, including off-label use, has contributed to a supply shortage, leaving many patients unable to access these medications. As health care providers and pharmaceutical companies navigate these challenges, GLP-1 receptor agonists will remain central to the evolving landscape of chronic disease management.
