Nurse knowledge aids management and safety.
- In addition to promoting increased insulin secretion to manage type 2 diabetes, glucagon-like peptide 1 also slow gastric emptying to promote weight loss.
- After testing in patients without type 2 diabetes, the FDA approved Wegovy (for chronic weight management).
- Nurse understanding of the drug risks and impact of shortages aids patient safety.
Charlotte Adams*, a 54-year-old woman, gained 30 pounds during menopause. She has no significant past medical history or comorbidities; however, the weight gain put her at an obese body mass index (BMI) of 30 kg/m². Concerned about her health because of a family history of cardiovascular disease and diabetes, Ms. Adams discusses weight loss medications with her primary care provider. The provider orders Wegovy®, a branded version of semaglutide.
Semaglutide belongs to a drug class known as glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and is currently marketed in injectable (Ozempic® and Wegovy®) and oral tablet (Rybelsus®) form. GLP-1 is an incretin hormone released in response to postprandial glucose, which promotes increased insulin secretion. GLP-1 RAs mimic incretin and work by activating receptors to cause the same response. This mechanism of action led to the initial approval of GLP-1 RAs to manage type 2 diabetes.
Focus on obesity treatment for lasting lifestyle change
Obesity in adults: Pharmacologic options for successful management
The benefits of GLP-1 RAs extend beyond glycemic control. GLP-1 activation also slows gastric emptying to prolong satiety, suppress appetite, and reduce cravings, which promotes weight loss. Therefore, this drug class offers benefits for obesity in patients with type 2 diabetes, a common comorbidity. These effects also have sparked the public’s interest in using them solely for weight loss, which has led to a demand that exceeds the drugs’ supply.
Semaglutide for weight loss
GLP-1 RA use for weight loss serves as an example of drug repurposing—the discovery of new therapeutic uses for a medication that the parent company didn’t initially intend to market. The discovery of additional benefits can expedite the development of new pharmacotherapy by leveraging existing treatments.
Eli Lilly is the parent company of exenatide, the first GLP-1 RA. The landmark drug gained Food and Drug Administration (FDA) approval in 2005 under the brand name Byetta®. This offered a breakthrough for the pharmaceutical industry as the medication demonstrated proven weight loss as an advantage over other type 2 diabetes agents available at the time. More than a decade later, Novo Nordisk pioneered the creation of a new GLP-1 RA, semaglutide. In 2017, the FDA approved the drug to treat type 2 diabetes under the brand name Ozempic.
Shortly after Ozempic gained approval, Novo Nordisk conducted a 68-week randomized, double-blind, placebo-controlled trial in participants without type 2 diabetes. Results demonstrated a mean weight loss of 14.9% with semaglutide compared to 2.4% with a placebo. Subsequently, the FDA approved the drug (Wegovy) in 2021 for chronic weight management.
Wegovy is indicated as an adjunct to lifestyle modification in adults who are either obese (BMI ≥30 kg/m²) or overweight (BMI of ≥27 kg/m²) with at least one weight-related comorbidity. No FDA-approved generic versions of injectable GLP-1 RAs for weight loss exist. The current oral formulation of semaglutide requires higher dosing for significant weight loss.
Concerning adverse effects
Semaglutide has safety risks. For example, a retrospective study by Ghusn and colleagues found a high incidence of adverse GI effects.
A narrative review conducted by Trujillo investigated the relative risks for associated adverse effects (such as GI symptoms, hypoglycemia, injection-site reactions, pancreatitis, neoplasms, gallbladder disease, and diabetic retinopathy) among three GLP-1 RAs when injected once weekly. Common GI effects included nausea, vomiting, and diarrhea; however, their frequency varied among the agents. Limited comparative clinical trials exist to assess overall efficacy, risks, and safety. (See Adverse effects.)
Adverse effects
Potential adverse effects of semaglutide and their underlying mechanisms include the following:
Acute kidney injury
The exact mechanism for this adverse effect is unknown. Pre-renal acute kidney injury may result from GI symptoms (vomiting, diarrhea), which contribute to dehydration and hypovolemia.
Gallbladder disease
The unclear association between semaglutide and gallbladder disease requires further investigation. Proposed risk factors include a change in bile acid production and secretion, suppressed cholecystokinin secretion, decreased emptying time, prolonged gallbladder refilling, and weight loss.
GI symptoms
GI symptoms, the most frequently reported adverse effect, results from semaglutide’s delayed gastric emptying (the drug’s action on appetite regulation). Symptoms include abdominal pain, constipation, nausea, and vomiting. Reports indicate that the incidence correlates with higher dosing, and onset occurs within the first month of therapy and upon dose escalation. Risk factors include rapid up-titration.
Pancreatitis
Drug action on GLP-1 receptors of the pancreas and exocrine ducts may cause cellular overgrowth, hyperplasia, and duct occlusion. Further studies are indicated.
Thyroid C-cell tumors
The underlying mechanism for this adverse effect isn’t clearly understood. The incidence of thyroid cancer is less than 1%, suggesting no significant risk. However, patients should receive counseling on the potential risk and be informed of symptoms (neck mass, dysphagia, dyspnea, persistent hoarseness). Use is contraindicated in patients with a personal or family history of thyroid cancer or multiple endocrine neoplasia syndrome type 2. Consultation with an endocrinologist is recommended in patients who develop elevated calcitonin concentrations or have thyroid nodules detected during imaging studies or physical exam.
Data from the FDA Adverse Event Reporting System (a database that reinforces continuous post-marketing surveillance to ensure drug safety) indicate a significant incidence of GI adverse effects in patients using semaglutide. Most concerning are recent case reports of drug-induced gastroparesis. The incidence of gastroparesis, a disorder that delays or stops food movement within the GI tract, is unsurprising considering that GLP-1 RAs induce weight loss by slowing gastric emptying.
Other effects, some rare, include medullary thyroid carcinoma. Novo Nordisk, the parent company of Ozempic and Wegovy, reported the incidence of acute pancreatitis in their clinical trials. However, these trials didn’t include patients with a history of pancreatitis. Storgaard and colleagues’ systematic review concluded that additional evidence is warranted to establish a stronger correlation between GLP-1 RAs and the risk for acute pancreatitis.
Recent popularity and shortages
Ms. Adams’ provider sends an electronic prescription to a local pharmacy. Due to its popularity, the medication is on backorder with no definitive date of availability. Later that week, an advertisement appears on Ms. Adams’ social media feed promoting telehealth services and “home delivery of generic semaglutide.”
Social media’s ability to amplify public awareness of certain medications can result in increased demand, which can lead to drug shortages. This has proven true with the dissemination of testimonials about the use of semaglutide for weight loss. The backorder of semaglutide has led patients to seek alternatives. Wegovy is the only FDA-approved brand of semaglutide indicated for weight loss; Ozempic’s approved use is limited to managing type 2 diabetes. The current supply deficit of Wegovy has led practitioners to start prescribing Ozempic off-label (non-FDA approved use). The shift to off-label prescribing of GLP-1 RAs has impacted product availability for patients with type 2 diabetes. However, despite sharing the same active ingredient, semaglutide, the two aren’t the same product per dosing, potency, and titration schedules.
Compounding semaglutide
Excited about the possibility of obtaining a generic form of semaglutide, Ms. Adams schedules a virtual consultation with a provider who orders the medication. Within a couple of days, the medication arrives in the mail. The delivery invoice indicates it came from a compounding pharmacy.
Ms. Adams follows the enclosed instructions on self-administration, and she begins to lose weight shortly after initiation without any adverse effects. However, 2 weeks into therapy, Ms. Adams experiences severe abdominal pain, nausea, and vomiting. She seeks emergency medical care.
Drug compounding occurs when a pharmacy combines raw active ingredients to prepare a medication not commercially available to meet a patient’s unique needs. For example, a provider can order a compounded formulation for a patient allergic to an ingredient (such as dyes or preservatives) in the commercial product. In this situation, compounding is necessary to provide the patient with a reformulated version that omits the allergen. Compounding also offers benefits in cases where patients can’t tolerate a medication’s route of administration. For example, a provider caring for a pediatric patient may prefer a prescription compounded into an oral liquid if the medication is available only as a tablet.
Pharmacies that engage in compounding must meet state-specific licensure requirements (aseptic technique, use of reputable sources when obtaining ingredients) and regulate production to ensure quality assurance and patient safety. However, compounded medications don’t undergo clinical trials and they’re not FDA approved.
When the demand for a branded medication exceeds its supply, the FDA places the active ingredient on an official drug shortage list. To address the deficit, legislation permits a compounding pharmacy to dispense a generic version temporarily. Semaglutide currently appears on the FDA drug shortage list, which allows for compounding. However, recent reports have shed light on the misinterpretation of legislation in which certain compounding pharmacies potentially obtain unapproved ingredients (such as various salt forms of semaglutide) to dispense formulations of “generic semaglutide” advertised online.
The FDA’s recent warning has raised public awareness that compounded products may contain different salt forms of active ingredients (for example, semaglutide-sodium and semaglutide-acetate), which haven’t undergone clinical trials to meet agency approval process requirements. As such, these adulterated variations remain unstudied substitutes. In addition to ensuring drug safety, clinical trials establish a drug’s kinetic profile; salt forms of semaglutide may have different effects, duration times, and underlying mechanisms of action.
Although compounding remains an acceptable pharmacy practice, the recent compounding of generic semaglutide has highlighted several patient issues. Reports indicate that some compounding pharmacies incorporate additives, such as vitamins, into their formulations, creating potential interactions and incompatibility. Contamination presents another concern if the dispensing pharmacy doesn’t adhere to aseptic techniques. Injectable semaglutide comes in multiuse pens, but some pharmacies have dispensed compounded semaglutide as a multidose vial, which poses the risk of improper self-administration and inaccurate dosing.
Telehealth services have a place in healthcare, offering patients convenience and accessibility to providers. The concern is that altered formulations of compounded generic semaglutide prescribed through telehealth and obtained from online pharmacies may lack FDA approval. Providers, nurses, and patients can use BeSafeRx (an FDA-sponsored online tool) to verify whether a pharmacy is licensed and reputable.
As Ms. Adams experienced, altered forms of semaglutide may lead to unintended adverse effects. The clinical profile of such medications may differ significantly with regard to absorption rate, duration of action, and potency. Furthermore, telehealth platforms limit a provider’s ability to perform objective assessments throughout pharmacotherapy.
Drug–drug interactions
Because semaglutide’s mechanism of action delays gastric emptying, it can interact with a patient’s other prescribed medications. A drug’s absorption site (stomach vs. intestines) depends on its pharmacokinetic profile. Delayed gastric emptying time enhances the absorption of co-administered drugs primarily absorbed from the stomach. In theory, this could increase the risk for adverse effects and toxicity. The monitoring parameters of pharmacotherapy with a narrow index also warrant consideration (for example, concurrent warfarin may require closer international normalized ratio monitoring). The small intestines absorb most oral medications; however, the effect of GLP-1 RAs remains a concern as their use can ultimately delay absorption and therapeutic actions of concurrent oral drug therapy, such as antibiotics and birth control.
Concurrent medications also may prove problematic secondary to overlapping therapeutic effects. For example, other antidiabetic agents (such as insulin, metformin, glyburide, sitagliptin, and canagliflozin) taken along with GLP-1 RAs potentiate hypoglycemic risk and may necessitate dose adjustments. Patients should never combine tirzepatide, an injectable with dual actions as a GLP-1 RA and glucose insulinotropic polypeptide, with any GLP-1 RA because it may result in fatal hypoglycemia. Providers must carefully manage concurrent pharmacotherapy that also raises blood glucose (for example, loop and thiazide diuretics), which can reduce GLP-1 RA efficacy. Furthermore, diuretics and other antihypertensives may potentiate dehydration secondary to GLP-1 RA-induced nausea and vomiting.
The risk of drug interactions increases when patients obtain products from unreputable sources; a detailed medication history may not be readily accessible by an online pharmacy. For example, knowledge of concurrent levothyroxine use may prove consequential since it also promotes weight loss. Currently, no clinically significant changes in the absorption or action of co-administered oral medications have been reported, but patients with impaired kidney function taking medications that require weight-based dosing warrant more frequent monitoring. The potential risks of drug interactions remain urgent and significant, underscoring the importance of thorough medication management and nurse–pharmacist collaboration.
Nurse–pharmacist collaboration
Expertise of the clinical pharmacy team significantly enhances medication reconciliation, a cornerstone of patient safety in the acute care setting. When nurses and pharmacists work together, they can successfully reconcile a patient’s medications and prevent medication-related errors. When a hospital admits a patient, the pharmacy team can provide invaluable insights to the nursing staff on weight loss drugs obtained from traditional as well as online platforms. Nurses should ask patients if they take compounded weight loss products and include them in the medication reconciliation. Any omission can have a direct impact on patient safety.
Nurses play an equally important role in encouraging patients to share this information with external providers and their primary pharmacy to ensure the entire healthcare team remains well-informed. These partnerships not only can reduce or possibly prevent patient harm but also can increase the reporting of adverse effects to facilitate post-marketing surveillance.
The clinical pharmacy team also can support nursing staff with medication reconciliation during pre-op patient management. Patients must have an empty stomach before undergoing any invasive procedure or surgery requiring anesthesia to prevent nausea and pulmonary aspiration, which can cause respiratory failure. Because semaglutide delays gastric emptying, food may remain in the abdomen beyond fasting guidelines, placing patients at risk for this serious complication. The clinical pharmacy team can provide in-service education about such situations and guide the healthcare team in conducting proper medication histories and making necessary adjustments. (See Collaboration beyond the hospital.)
Collaboration beyond the hospital
Nurse–pharmacist collaboration, as identified by Ravi and colleagues, extends beyond acute care settings, highlighting the integral role of community pharmacists in patient safety. Community pharmacists improve medication safety by providing community-dwelling patients with further insight into interactions and adverse effects that require medical attention and educating them on the importance of dose titration and proper administration of weight loss drugs.
Unlike patients in acute care settings, patients living in the community don’t receive continuous monitoring. They must take an active role in their medication management, which relies heavily on nurse-to-patient education. Collaboration with pharmacists equips nursing professionals with up-to-date knowledge to educate patients and empower them to take accountability for their health and make informed decisions about their medication.
Nursing implications
Fortunately, Ms. Adams doesn’t suffer any life-threatening complications. Laboratory tests, a gastric emptying study, and a computed tomography scan of the abdomen are unremarkable. She’s admitted to the hospital for 24 hours to receive I.V. fluids and ondansetron (to manage nausea and vomiting). Ms. Adams’ nurse considers this experience an opportunity to learn more about the therapeutic actions of GLP-1 RAs and the potential risks and disadvantages of obtaining these medications through virtual providers and online pharmacy sources.
Although GLP-1 RAs have demonstrated efficacy and offer hope, obesity remains challenging and individual outcomes vary. The psychological consequences and stigma of obesity require a solid provider–patient relationship. Providers who genuinely connect with their patients can better empower them to take an active role in their care and incorporate healthy lifestyle changes. Although these medications can prove beneficial, they’re not a cure-all. Nurses can provide education about lifestyle modifications, such as reducing caloric intake, increasing physical activity, and creating sustainable lifelong healthy habits to preventing rebound weight gain after discontinuing pharmacotherapy.
Nurses play a substantial role in promoting health and educating patients about medications. As advocates for patients considering GLP-1 RA therapy for obesity, nurses can provide further insight and assist patients in making informed decisions. Familiarity with current medication-related trends and risks positions nurses to provide optimal care and evidence-based patient education. Nurses must learn all they can about these novel medications and their adverse effects, risks, and benefits, as well as their compounded substitutes. AN
*Name is fictitious.
Christopher Hanley is an associate professor and chair of clinical pharmacology at Manhattanville University’s School of Nursing and Health Sciences in Harrison, New York. Cindy Paradiso is an assistant professor at Pace University’s Lienhard School of Nursing in the College of Health Professions in Pleasantville, New York, and a clinical quality specialist at White Plains Hospital in White Plains, New York.
American Nurse Journal. 2025; 20(6). Doi: 10.51256/ANJ062512
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Key words: glucagon-like peptide 1 receptor agonists, Ozempic, Wegovy, Rybelsus, semaglutide, weight loss
