Introduction

Anaphylaxis is a serious, systemic hypersensitivity reaction characterized by rapid onset and the potential for life-threatening progression within minutes. In many cases, symptoms escalate in seconds, turning an ordinary moment at a restaurant, school event, or family gathering into a medical emergency. If left untreated, anaphylaxis may lead to loss of consciousness, cardiac arrest, or death. According to the Allergy and Asthma network, approximately 1 in 20 Americans have experienced anaphylaxis. Among individuals with food allergies, 42% of children and 51% of adults report a history of severe reactions. The economic burden is also substantial, with an estimated $1.2 billion in annual direct medical costs in the United States, including roughly $294 million attributed to epinephrine prescriptions alone. Anaphylaxis is associated with approximately 225 deaths per year in the U.S., and notably, about half of all episodes occur at home.

Epinephrine remains the only medication capable of reversing the life-threatening symptoms of anaphylaxis and is universally recognized as the cornerstone of management. In theory, that makes the solution sound straight forward—recognize symptoms and administer epinephrine immediately. In practice, it’s more complicated. Despite clear guideline recommendations, epinephrine continues to be underutilized. In a nationwide survey conducted by Wood and colleagues, 52% of patients who had previously experienced anaphylaxis had never received a prescription for an epinephrine auto-injector (EAI), and 60% did not have one currently available. Barriers include needle phobia, fear and anxiety surrounding device use, lack of confidence in administration technique, and misconceptions that a prescription is unnecessary. Delayed administration is associated with more severe outcomes, including biphasic reactions and increased risk of fatality. When it comes to anaphylaxis, hesitation can be costly—timely epinephrine use is strongly correlated with improved survival.

This gap between what should happen and what actually happens has fueled interest in alternative delivery systems. Anaphylm, an investigational sublingual epinephrine film developed by Aquestive Therapeutics, is being studied as a potential alternative to injectable epinephrine products.The film is small and lightweight, designed to dissolve under the tongue without the need for water or swallowing, and is packaged in a compact, weather-resistant format. While still under regulatory review, the concept raises important questions for pharmacists—Could a needle-free option improve willingness to carry epinephrine? Would simpler administration reduce delays in real-world emergencies? As the landscape of anaphylaxis treatment evolves, pharmacists will play a critical role in evaluating emerging therapies and translating new options into safe, practical patient care.

Overview of Anaphylaxis

Hypersensitivity reactions are immune-mediated responses that result in tissue injury and clinical symptoms. They are classified into four types (I-IV) based on their underlying immunologic mechanism and timing of presentation. The chart below outlines the key features and common examples of each type.

As a type I hypersensitivity reaction, anaphylaxis represents the most acute and potentially life-threatening immune response. The table below highlights common triggers and causes that pharmacists should be aware of.

Recognizing and responding to anaphylaxis is a critical skill for all healthcare personnel. Prompt anaphylaxis treatment should be considered when a patient presents with generalized symptoms such as hives, or more serious, potentially life-threatening signs including hypotension, respiratory distress, significant swelling of the lips or tongue, or involvement of more than one body system. Other common clinical manifestations of anaphylaxis include:

• Respiratory—Sensation of throat closing, stridor (high-pitched sound while breathing), shortness of breath, wheezing, or cough
• Gastrointestinal—Nausea or vomiting, diarrhea, abdominal pain
• Cardiovascular—Dizziness or fainting, tachycardia, hypotension
• Skin mucosal—Generalized hives, itching, swelling of lips, face or throat
• Neurological—agitation, convulsions, acute change in mental status, sensation of impending doom

If a patient exhibits any of these signs, especially when multiple systems are involved, immediate recognition and intervention is essential. Prompt action can be lifesaving and prevents progression to severe or fatal outcomes. Here is what to do when anaphylaxis is suspected:

1. Assess airway, breathing, and circulation (ABCs)
2. Administer epinephrine immediately
3. Call emergency medical services
4. Place the patient in supine position

Current Epinephrine Options

When anaphylaxis occurs, epinephrine is the lifesaving first-line treatment, and timely administration is critical. The current FDA-approved epinephrine options are:

• Neffy® nasal spray by ARS Pharma
• EpiPen® / EpiPen Jr® or their generics
• Auvi-Q® Auto-Injector
• Authorized generic of Adrenaclick® by Amneal Pharmaceuticals
• Generic of EpiPen® / EpiPen Jr® by Teva Pharmaceuticals
• EpiPen® / EpiPen Jr® and authorized generics by Viatris (formerly Mylan)

Even with multiple options on the market, no form of epinephrine has been shown to be more or less effective than another. In practice, insurance coverage often determines which option a patient receives. Most auto-injectors and the nasal spray come in two packs to ensure a backup dose is available in case a second injection is needed or in case the first device malfunctions. The table below shows a comparison between the auto-injector and nasal spray version of epinephrine.

Despite the availability of multiple epinephrine options, there are several challenges to consider. Patients and caregivers may become confused when faced with different devices or administration instructions, and fear of needles can lead to hesitation or improper use. In fact, a study from the National Institute of Health found that EAIs are used incorrectly 35-45% of the time. Access and insurance coverage can also be limiting factors, particularly for nasal spray options, which are less widely covered.

While epinephrine can be lifesaving, it is important for patients and healthcare providers to be aware of potential side effects and what to expect after administration. Side effects include:

• Tachycardia
• Arrhythmias
• Palpitations
• Hypertension
• Headache
• Tremor, weakness
• Pallor, sweating
• Nausea and vomiting
• Nervousness and anxiety
• Pain, redness at the injection site
• Tissue necrosis (if extravasated)

What is Sublingual Epinephrine?

For decades, epinephrine has been the frontline defense against anaphylaxis, now it is getting a needle-free upgrade. A new oral form of epinephrine is currently in clinical development, representing the first and only oral delivery option for Type I allergic reactions, including anaphylaxis. This innovative formulation contains a prodrug of epinephrine that is designed to be portable while achieving rapid absorption through sublingual administration.

The oral epinephrine is about the size of a postage stamp and weighs less than an ounce. Its packaging is even thinner and smaller than the average credit card, making it easy to carry in a pocket. It can also withstand weather conditions like rain or sunlight. 

Anaphylm offers several advantages to patients and providers including:

With oral epinephrine on the horizon, the future of anaphylaxis management could be more convenient, safer and patient-friendly than ever before.

Challenges and Considerations for Anaphylm

While oral epinephrine offers exciting benefits, there are some current limitations to be aware of. On January 30, 2026, the FDA issues Anaphylm a Complete Response Letter, meaning the product was not approved in its current form. The agency raised concerns about usability, including trouble opening the pouch and correctly placing the film under the tongue. Importantly, these issues were related to the packaging and administration, rather than the drug’s safety or efficacy. 

The main issues involve practicality during emergency situations and the need for additional pharmacokinetic data. The company developing the product believes these concerns can be resolved quickly, with plans to resubmit as early as summer 2026. The FDA is requesting further information on packaging, labeling, and pharmacokinetics, and details on insurance coverage remain uncertain at this time. 

Despite these hurdles, oral epinephrine remains a promising innovation that could significantly improve the accessibility and ease of anaphylaxis treatment once these issues are addressed.

The Final Consensus of Anaphylm for Patients

Anaphylaxis remains one of the most urgent and high-stakes emergencies pharmacists may encounter, and rapid access to epinephrine continues to be the mainstay of treatment. While current auto-injectors and nasal formulations are effective, challenges such as device confusion, administration errors, and access barriers still exist. Emerging innovations like oral epinephrine have the potential to reshape the future of anaphylaxis management by improving portability, ease of use, and patient confidence. As the treatment landscape continues to evolve, pharmacists will remain at the forefront to educate patients, navigate coverage barriers, and ensure that when seconds matter the most, lifesaving therapy is ready and within reach. 

APPE Student, Hailey Montour

References

Allergy & Asthma Network. Anaphylaxis Statistics. Accessed February 26, 2026. https://allergyasthmanetwork.org/anaphylaxis/anaphylaxis-statistics/ 

Aquestive Therapeutics. Anaphylm®. Accessed February 26, 2026. https://aquestive.com/anaphylm/ 

Aquestive Therapeutics. Sublingual epinephrine (Anaphylm®) provides consistent pharmacokinetics in both adult and pediatric subjects. Accessed February 26, 2026. https://www.aquestivedata.com/pdfs/sublingual_epinephrine_anaphylm_provides_consistent_pharmacokinetics_in_both_adult_and_pediatric_subjects.pdf

Centers for Disease Control and Prevention (CDC). Recognizing and Responding to Anaphylaxis. Accessed February 26, 2026. https://www.cdc.gov/vaccines/covid-19/downloads/recognizing-responding-to-anaphylaxis-508.pdf 

Food Allergy Research & Education (FARE). Epinephrine Options and Training. Accessed February 26, 2026. https://www.foodallergy.org/resources/epinephrine-options-and-training 

Food Allergy Research & Education (FARE). What Epinephrine Option Is Best for You? Accessed February 26, 2026. https://aafa.org/wp-content/uploads/2026/02/what-epinephrine-option-is-best-for-you.pdf 

Kraus CN, Wargacki S, Golden D, Lieberman J, Greenhawt M, Camargo CA Jr. Integrated phase I pharmacokinetics and pharmacodynamics of epinephrine administered through sublingual film, autoinjector, or manual injection. Ann Allergy Asthma Immunol. 2025;134(5):580-586. doi:10.1016/j.anai.2025.01.006

Ziyar A, Kwon J, Li A, Naderi A, Jean T. Improving epinephrine autoinjector usability and carriage frequency among patients at risk of anaphylaxis: a quality improvement initiative. BMJ Open Qual. 2022;11(3):e001742. doi:10.1136/bmjoq-2021-001742

Introduction

For nearly two decades, GLP-1 receptor agonists have steadily reshaped metabolic care since the first agent reached the U.S. market in 2005. Initially developed for Type II diabetes, these medications quickly proved their ability to improve glycemic control and significantly lower A1C. Over time, their role expanded beyond glucose management, becoming widely recognized for promoting weight loss through appetite suppression and earlier satiety. Additional benefits, including cardiovascular risk reduction and kidney-protective effects, have further solidified their place in therapy. In 2025, polling from the Kaiser Family Foundation (KFF) reported that 1 in 8 U.S. adults were currently taking a GLP-1 medication for weight loss, diabetes, or another indication, highlighting just how mainstream these therapies have become.

Meanwhile, data from the Centers for Disease Control and Prevention (CDC) show that over 40% of U.S. adults are living with obesity, underscoring the growing severity of the obesity epidemic. The CDC map below illustrates obesity prevalence across the U.S. As obesity rates continue to rise, GLP-1 therapies have emerged as central players in addressing one of the nation’s most urgent public health challenges.

Despite their popularity and clinical benefits, GLP-1 therapies are not without barriers. High cost, gastrointestinal adverse effects, and the burden of weekly subcutaneous injections can limit initiation and long-term adherence. For some patients, needle aversion alone is enough to avoid treatment. That landscape shifted in December 2025, when the U.S. Food and Drug Administration (FDA) approved a once-daily oral tablet version of Wegovy (semaglutide) for chronic weight management, with availability beginning in January 2026. A report by health data firm Truveta found that within the first six weeks of the oral Wegovy launch, 21.1% of patients on the pill had transitioned from an injectable version of Wegovy, while 15.8% had switched from Zepbound. The arrival of an oral option has the potential to expand access. As questions inevitably increase, pharmacists will be on the front lines, making now the perfect opportunity to review what this new formulation means for practice and the evolving obesity treatment landscape. 

Background: GLP-1 Therapy Landscape

GLP-1 receptor agonists work by mimicking the body’s natural GLP-1 hormone, which plays several key roles in regulating metabolism:

• Stimulates glucose-dependent insulin secretion from the pancreas
• Suppresses glucagon release, helping to prevent excessive glucose production
• Slows gastric emptying, promoting a feeling of fullness

Together, these effects lead to lower blood glucose levels and weight loss by reducing appetite and increasing early satiety, making GLP-1 therapies powerful tools for both diabetes and obesity management.

The table below provides an overview of available GLP-1 therapies, including the newly approved oral Wegovy.

Besides diabetes and obesity management, GLP-1 drugs have shown many other potential benefits including:

• Lowering blood pressure
• Improving lipid disorders
• Improving fatty liver disease
• Reducing cardiovascular risk
• Decreases inflammation
• Reducing risk of kidney disease

It is common for patients starting GLP-1 therapy to experience side effects during the first few weeks, including nausea, vomiting, headache, dizziness, and diarrhea. These effects are usually temporary and tend to subside as the body adjusts, which is why GLP-1 medications are typically titrated from a low dose to a higher dose to help minimize discomfort. 

Although rare, serious adverse events can occur, including gallstones, pancreatitis, medullary thyroid cancer, acute kidney injury, and worsening of diabetes-related retinopathy. Monitoring and patient counseling are essential to help identify and manage these risks early.

Is Oral Wegovy the Same as Injectable Wegovy?

So, with all that context, let’s dive into the pill form of Wegovy and answer questions on how this may or may not differ from the standard injection.

Wegovy (semaglutide) tablets are 25 mg once daily oral tablets designed for chronic weight management and cardiovascular risk reduction. They are designed to be used alone and should not be combined with other GLP-1 injections. The oral tablets contain the same active ingredient as the injectable formulation, with an identical mechanism of action and comparable safety and efficacy profiles demonstrated in clinical trials.

Data from the OASIS 4 (oral semaglutide) and STEP 5 (injectable semaglutide) trials highlight similar outcomes across key endpoints. The table below provides a side-by-side comparison of selected results from these studies.

The primary difference between the injection and the pill lies in how the drug is absorbed. The oral Wegovy tablet uses a technology called SNAC (sodium N-(8-[2-hydroxybenzoyl]amino)caprylate) to overcome the low bioavailability typical of oral semaglutide. SNAC works by creating a temporary, localized pH-buffering effect that allows semaglutide to pass directly through the stomach lining into the bloodstream, protecting it from enzymatic degradation along the way. The image below illustrates the absorption mechanism and the protective role of SNAC. 

To achieve maximum benefit, Wegovy tablets should be taken on an empty stomach first thing in the morning, with no more than 4 oz of water, and at least 30 minutes before the first meal of the day. It is important to note that injectable Wegovy can be administered without regard to food, beverages, or time of day.

Another key difference between the two formulations is dosing flexibility. The injectable formulation is manufactured in multiple dose strengths to allow for stepwise titration:

• 0.25 mg once weekly for 4 weeks
• 0.5 mg once weekly for 4 weeks
• 1 mg once weekly for 4 weeks
• 1.7 mg once weekly for 4 weeks
• Maintenance dose: 2.4 mg once weekly

The oral tablet is only available in a single 25 mg strength offering a fixed-dose daily regimen. A higher milligram dose is required to achieve therapeutic systemic exposure. Although the oral tablet does not incorporate a stepwise titration schedule, clinical trial data demonstrated acceptable tolerability with the fixed dose-regimen.

What About Rybelysus?

You might be wondering: What about Rybelsus? After all, it’s also an oral formulation of semaglutide. While it is true that there are now two oral semaglutide products on the market, they differ significantly in indication and dosing.

Oral Wegovy is specifically approved for chronic weight management at a 25 mg daily dose, whereas Rybelsus is FDA approved for Type II diabetes with a maximum dose of 14 mg daily. The higher dose used in oral Wegovy is designed to achieve greater weight reduction, while Rybelsus dosing is optimized primarily for glycemic control. Although Rybelsus can still promote modest weight loss, oral Wegovy is formulated and studied specifically for obesity treatment at a higher therapeutic exposure. 

Despite these differences in indication and dosing, both products contain semaglutide and therefore share a similar mechanism of action and adverse effect profile.

Advantages and Challenges of Oral GLP-1 Therapy

So how does oral Wegovy stack up against the injectable version? The chart below highlights the key advantages and challenges of the oral formulation.

The Bottom Line on the Outlook of Oral GLP-1 Therapy

The introduction of oral Wegovy marks a significant advance in obesity management, offering patients a convenient, needle-free alternative to the weekly injectable while maintaining a comparable safety and efficacy profile. With over 40% of U.S. adults living with obesity, this new formulation provides an important tool to help address one of the nation’s most pressing public health challenges.

The role of pharmacists is pivotal to guide patients on proper administration, emphasizing the importance of taking the tablet on an empty stomach with limited water, managing gastrointestinal side effects, and supporting daily adherence are all key to achieving the best outcomes.

While oral Wegovy removes the injection burden and may improve patient acceptance, challenges such as variable absorption, strict dosing requirements, and cost considerations remain. By understanding these nuances and providing proactive counseling, pharmacists can help patients’ safety and effectively use oral Wegovy, ultimately contributing to broader efforts to combat obesity and improving long-term metabolic health in the U.S.

APPE Student, Hailey Montour

References

Aroda VR, Blonde L, Pratley RE. A new era for oral peptides: SNAC and the development of oral semaglutide for the treatment of type 2 diabetes. Rev Endocr Metab Disord. 2022;23(5):979-994. doi:10.1007/s11154-022-09735-8

BioSpace. Oral Wegovy brings in thousands of new GLP-1 patients. https://www.biospace.com/business/oral-wegovy-brings-in-thousands-of-new-glp-1-patients. Accessed February 25, 2026.

Centers for Disease Control and Prevention. Adult obesity prevalence maps. https://www.cdc.gov/obesity/data-and-statistics/adult-obesity-prevalence-maps.html. Accessed February 25, 2026.

Centers for Disease Control and Prevention. Summary health statistics: National Health Interview Survey, 2021–August 2023. https://www.cdc.gov/nchs/products/databriefs/db508.htm#:~:text=2021%E2%80%93August%202023.-,Summary,adults%20did%20not%20change%20significantly. Accessed February 25, 2026.

Cleveland Clinic. GLP-1 agonists. https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists. Accessed February 25, 2026.

Kaiser Family Foundation. 1 in 8 adults say they are currently taking a GLP-1 drug for weight loss, diabetes, or another condition, even as half say the drugs are difficult to afford. https://www.kff.org/public-opinion/poll-1-in-8-adults-say-they-are-currently-taking-a-glp-1-drug-for-weight-loss-diabetes-or-another-condition-even-as-half-say-the-drugs-are-difficult-to-afford/. Accessed February 25, 2026.

Latif W, Lambrinos KJ, Patel P, et al. Compare and contrast the glucagon-like peptide-1 receptor agonists (GLP1RAs) [Updated 2024 Feb 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572151/. Accessed February 25, 2026.

NovoMedlink. Wegovy: Obesity treatments. https://www.novomedlink.com/obesity/products/treatments/wegovy.html?_gl=1*18bf07x*_ga*MzY1MjUwMzQxLjE3NzIwMzE3NTc.*_ga_F40L5513K4*czE3NzIwMzE3NTYkbzEkZzAkdDE3NzIwMzE3NTYkajYwJGwwJGgw. Accessed February 25, 2026.

Introduction

Since the approval of the first statin in 1987, statin therapy has transformed the landscape of cardio›vascular medicine. Statins were originally developed to lower cholesterol levels and manage hypercholesterolemia; however, they soon proved beneficial for cardiovascular prevention, as elevated cholesterol is a major risk factor for cardiovascular disease. These medications quickly became a cornerstone in the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), particularly among patients with diabetes, hypertension, and other cardiovascular risk factors. Statins not only reduce the incidence of heart attacks and strokes but also decrease overall mortality, making them one of the most widely prescribed drug classes in the United States. According to the Centers for Disease Control and Prevention (CDC), approximately 47 million U.S. adults were taking a statin in 2023, emphasizing their widespread use in clinical practice. 

Despite their established benefits in cardiovascular health, concerns have emerged that statins may contribute to neurocognitive decline, such as memory impairment and dementia. Understanding whether these concerns are supported by evidence is critical for pharmacists, who play a central role in medication counseling and patient education. This raises the question: what does the current scientific evidence reveal about statins and cognitive function?

These CDC maps illustrate the prevalence of high cholesterol (above) and heart disease (below) across U.S. counties from 2018 to 2020. The similar geographic patterns highlight the strong association between high cholesterol and increased heart disease risk.

What are Statins?

Statin medications are inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase enzyme in the liver, which reduces the synthesis cholesterol. Inhibition of this rate-limiting step effectively lowers total cholesterol, low-density lipoprotein (LDL), and triglyceride levels, thereby reducing the risk of atherosclerotic plaque formation and cardiovascular events. FDA-approved statins include atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, and pitavastatin.

Statins are used to manage a variety of lipid disorders and prevent cardiovascular events. Indications for statin therapy include:

• Primary or mixed hyperlipidemia
• Hypertriglyceridemia
• Familial hypercholesterolemia
• Atherosclerosis
• Primary prevention of ASCVD
• Secondary prevention in patients with clinical ASCVD

In adults without established cardiovascular disease, statins are used to reduce overall cardiovascular risk. Common risk factors and enhancers of ASCVD include: 

• Diabetes mellitus
• Hypertension
• Obesity
• Smoking or tobacco use
• Chronic kidney disease
• Chronic inflammatory conditions
• Metabolic syndrome

In patients with clinical ASCVD, statins are indicated to prevent recurrent cardiovascular events. Conditions classified under clinical ASCVD include:

• Myocardial Infarction
• Stroke or transient ischemic attack
• Coronary artery disease
• Peripheral artery disease
• Post-revascularization

Statins are generally well tolerated. The most commonly reported adverse effects include:

• Musculoskeletal symptoms: myalgia, arthralgia, soreness, fatigue
• Gastrointestinal symptoms: diarrhea, constipation, nausea, flatulence

Rarely, statins may cause liver enzyme elevations or serious rhabdomyolysis, but these events are uncommon.

Understanding Dementia and Cognitive Decline

Dementia is a neurocognitive disorder characterized by progressive decline in memory, thinking, and reasoning, which can significantly impact daily functioning. Currently, Dementia affects an estimated 55 million people worldwide, with this number projected to nearly triple by 2050. As the disease progresses, patients may experience behavioral changes, personality shifts, and increased dependence on caregivers. Below is a table describing the different types of dementia.

Several modifiable risk factors have been identified, including lack of physical activity, uncontrolled diabetes, hypertension, hearing loss, and tobacco or alcohol use. According to the CDC, up to 45% of all dementia cases may be preventable or delayed through lifestyle modification and management of chronic conditions. With the global burden of dementia rising, preventative strategies are critical and understanding the impact of medications such as statins on cognitive health is an important aspect of care.

Historical Concerns About Statins and Cognition

Now that we delved into the many features of statins and dementia, where did the growing fear that statins might cause dementia originate from? A couple of factors contributed. 

First, in 2012, the FDA issued a safety communication regarding potential cognitive effects of statin therapy. The communication noted that memory loss and confusion had been reported, but emphasized that these cognitive side effects were minor and reversible upon discontinuation of therapy. 

Second, public concern is fueled by a common misconception about the brain’s dependence on cholesterol. Some worry that lowering blood cholesterol with statins could harm brain function, but that is not supported by physiology. Although it is true that the brain relies on cholesterol for proper function, the brain synthesizes its own cholesterol independently of blood cholesterol levels through the central nervous system. Early case reports and small observational studies also suggested a possible link between statin use and cognitive changes, which further amplified public concern. 

Given these factors, it is understandable why some patients and clinicians may perceive a connection between statin therapy and dementia. But what does the scientific evidence actually show? To answer this, we can turn to a recent systematic review and meta-analysis from 2025 to examine the most recent evidence on this topic.

What Does the Evidence Say?

A 2025 systematic review and meta-analysis analyzed data from 55 observational studies including over 7 million participants to investigate whether statin use is associated with dementia risk. The analysis found that statin therapy was associated with a statistically significant reduction in the risk of all-cause dementia, effectively refuting the misconception that statins negatively impact cognitive function. Among individual statins, rosuvastatin showed one of the strongest associations with reduced dementia risk. 

Several potential mechanisms have been proposed to explain the neuroprotective effects of statins:

Despite these findings, the 2012 safety communication regarding cognitive effects of statins remains relevant. Statins can occasionally cause temporary cognitive changes, such as memory lapses or “mental fuzziness”. These events are rare, generally mild, and reversible upon discontinuation of statin therapy. A proposed mechanism involves reduced coenzyme Q10 (ubiquinone) levels, as statins inhibit the pathway responsible for its synthesis. Since coenzyme Q10 is essential for mitochondrial energy production, temporary reductions may lead to mild cognitive symptoms in some individuals. Importantly, these effects do not indicate permanent dementia.

Implication for Pharmacists and Patients

Pharmacists play a key role in the community by providing medication counseling and education. This puts pharmacists in a unique position to address common misconceptions related to medications and to give peace of mind to patients who may worry about initiating statin drugs. When addressing patient concerns about statin therapy and cognition, key counseling points include:

• Emphasizing that serious or permanent cognitive impairment is not associated with statin use
• Explaining that temporary memory lapses are rare side effects of statins, but are not serious and reversible
• Highlighting that statins have cardiovascular and potential neuroprotective benefits 
• Encouraging adherence statin therapy to maximize long-term health outcomes

Patient education should also include lifestyle interventions to reduce both cardiovascular and dementia risk, such as regular exercise, blood pressure control, diabetes management, and avoidance of tobacco or alcohol.

Conclusion

Statins remain a cornerstone for cardiovascular health and are generally safe and well tolerated medications. While public concern has emerged regarding potential cognitive effects, evidence shows that statin use is not associated with an increased risk of dementia and may actually provide neuroprotective benefits. Several potential mechanisms have been proposed to explain these effects, though further research is needed to clarify the exact pathways by which statins influence brain health. Temporary cognitive changes are rare, mild, and reversible and do not outweigh the substantial cardiovascular and potential neurocognitive benefits of therapy. For pharmacists, understanding this evidence is critical for patient counseling, addressing misconceptions, and promoting adherence to ensure that patients receive the full spectrum of benefits statins offer. 

APPE student, Hailey Montour

References

Alzheimer’s Society (UK). Types of Dementia. Accessed February 24, 2026. https://www.alzheimers.org.uk/about-dementia/types-dementia

American Heart Association. 2018 AHA/ACC Guideline on the Management of Blood Cholesterol. Circulation. 2019;139(25):e1082–e1143. doi:10.1161/CIR.0000000000000678

Atrium Health. The facts about statins and dementia risk. Accessed February 24, 2026. https://www.atria.org/education/the-facts-about-statins-and-dementia-risk/

Bays HE, Taub PR, Epstein E, et al. Ten things to know about ten cardiovascular disease risk factors. Am J Prev Cardiol. 2021;5:100149. Published 2021 Jan 23. doi:10.1016/j.ajpc.2021.100149

Centers for Disease Control and Prevention. Alzheimer’s Disease and Preventing Cognitive Decline. Accessed February 24, 2026. https://www.cdc.gov/alzheimers-dementia/prevention/index.html

Centers for Disease Control and Prevention. Cholesterol Facts & Statistics. Updated 2023. Accessed February 24, 2026. https://www.cdc.gov/cholesterol/data-research/facts-stats/index.html

Centers for Disease Control and Prevention. What is dementia? Updated March 2024. Accessed February 24, 2026.

Available at: https://www.cdc.gov/alzheimers-dementia/about/index.html

Endo A. A historical perspective on the discovery of statins. Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(5):484-493. doi:10.2183/pjab.86.484

Sizar O, Khare S, Patel P, et al. Statin Medications. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; Updated February 29, 2024. Accessed February 24, 2026. https://www.ncbi.nlm.nih.gov/books/NBK430940/

U.S. Food and Drug Administration. FDA Drug Safety Communication: Important Safety Label Changes to Cholesterol‑Lowering Statin Drugs. Accessed February 24, 2026. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-important-safety-label-changes-cholesterol-lowering-statin-drugs

van Vliet P. Cholesterol and late-life cognitive decline. J Alzheimers Dis. 2012;30 Suppl 2:S147-S162. doi:10.3233/JAD-2011-111028

Westphal Filho FL, Moss Lopes PR, Menegaz de Almeida A, et al. Statin use and dementia risk: A systematic review and updated meta-analysis. Alzheimers Dement (N Y). 2025;11(1):e70039. Published 2025 Jan 16. doi:10.1002/trc2.70039

Overview

There is often negative stigma surrounding the idea of bariatric surgery as some may assume it is a shiftless intervention for weight loss in which the patient does not put effort into their weight loss goals. Therefore, some may find it interesting to learn that bariatric surgeries are vital procedures offered when all other options have been exhausted, and these procedures often require a great deal of work from the patient to maintain proper healthcare management post operation. In relation to general health and the maintenance of other comorbidities, bariatric procedures may limit the absorption of enteral products, including vitamins, minerals, and other necessary medications. Because of altering drug distribution patterns and the impact of weight reduction on chronic disease states, long-term medication regimens may need to be adjusted.

Background of Bariatric Surgeries

Body mass index (BMI) is used by the World Health Organization to classify obesity. The normal range is 18.5 to 24.9 kg/m2, overweight is 25 to 25.9 kg/m2, obese class I is 30 to 34.9 kg/m2, obese class II is 35 to 35.9 kg/m2, and obese class III is 40 to 49.9 kg/m2. There are many reasons as to why BMI may be high including lifestyle, genetics, age, medications, and other comorbidities. Obesity is a concern as the increase in fat tissue around organs can lead to dysregulation of body systems, and in attempt to address these problems, a number of therapy approaches have been developed including lifestyle changes, weight-loss drugs, and bariatric surgery. For the treatment of class III obesity, bariatric surgery is now more effective than lifestyle modifications. Between 50% and 75% of excess body weight can be lost with bariatric surgery, and some research indicates that weight maintenance can continue for up to 16 years following the procedure. 

Based on their functions, bariatric surgical techniques can be divided into three main classifications: malabsorptive, combination, and restrictive. Laparoscopic adjustable gastric banding, vertical banded gastroplasty, and sleeve gastrectomy are examples of restrictive surgeries. However, the vertical banded gastroplasty is no longer implemented because of significant complications. Roux-en-Y (RYGB) and biliopancreatic diversion with a duodenal switch are examples of combined restrictive and malabsorptive surgeries. Currently, the most popular bariatric operations carried out globally are RYGB and sleeve gastrectomy.

Source and Images: Original Artwork by Rogelio Avila. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC9270090/ 

Gastric bypass patients who undergo a restrictive procedure involves separating a small pouch of their stomach from the rest of their stomach allowing them to feel fully satiated with little food. A malabsorptive procedure, where this pouch is then directly connected to the lower part of the jejunum, bypassing the whole duodenum and a part of the jejunum, causes the digestive system to absorb fewer calories, fat and nutrients.

Not all patients are candidates for bariatric surgery. Based on guidelines provided by American Society for Metabolic and Bariatric Surgery (ASMBS) and Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), which rely on an individual’s BMI and comorbid conditions, most patients are qualified with a BMI ≥ 40 kg/m² with no comorbid conditions. A patient can qualify with a lower BMI if their health is compromised. This includes a BMI of 35-39.9 kg/m² having at least one severe obesity-related co-morbidity such as obstructive sleep apnea, MASH, or obesity-related cardiomyopathy or patients with a BMI of 30-34.9 kg/m² that suffer from metabolic syndrome or diabetes mellitus uncontrolled by medical therapy.

How Gastric Bypass May Affect Medications

• Increased gastric pH potentially influencing the solubility and/or dissolution of drugs
• The proximal small intestine is bypassed, reducing the drug transit time and potentially limiting absorption
• Substantial postoperative weight loss may reduce drug clearance of high-extraction-ratio drugs
• The volume of distribution for lipophilic medications that transfer to body fat may also be impacted by bariatric surgery (e.g. drug potency)
• Metabolic activity of certain enzymes may decrease after bariatric surgery (e.g. glucuronidation)

Examples of Some Medications Requiring Extra Attention

• Lithium: Due to decreased stomach surface area, increased gastric pH, or postoperative weight loss, lithium’s absorption and clearance can vary, which may increase the risk of lithium toxicity. Clinicians should closely evaluate serum lithium levels for the first six weeks following surgery, then every two weeks until six months afterwards, and then monthly for up to a year after surgery due to the lack of official guidelines.

• Lipophilic Medications: Bile acids serve as surfactants to increase the solubility of other medications, including lipophilic medications. The bypass procedure decreases bile acid secretion, which could result in lipophilic medications not fully dissolving and being absorbed.

• In General: Easy-to-digest medication formulations, such as liquids, oral dissolving, chewable, or immediate-release tablets, should be used post-bariatric surgery. Restarting diuretics should be handled carefully, particularly in the early postoperative period when fluid intake may be restricted. In addition, after restrictive and malabsorptive bariatric surgery, the absorption of oral contraceptives may be decreased, especially if diarrhea persists. Alternative non-oral forms of contraception should be tried.

Why Medication Safety Matters After Bariatric Surgery

Because of the associated bodily modifications and significant weight loss, bariatric surgery may have an impact on the pharmacokinetics of certain medications. Therefore, in order to obtain improved effectiveness while also preventing toxicity, it is vital to identify possible changes and adjust patients’ medication dosages.

Supplement and Lifelong Nutritional Considerations

Because of the significant risk of micronutrient deficiencies caused by decreased intake, altered digestion, and malabsorption following a gastric bypass, lifelong nutritional care is needed. In order to maintain lean mass, patients need continuous dietitian-guided care that emphasizes a sufficient protein intake (≥60 g/day, ideally ≥1.1 g/kg ideal weight/day) and regular physical activity. Since deficits in vitamin B1, B12, folate, vitamin D, calcium, iron, and zinc are common even despite normal supplementation, lifetime multivitamin and trace-element supplementation is strongly recommended. 

Immediate thiamine therapy for any patient experiencing persistent vomiting, systematic B12 supplementation with lifetime monitoring, daily vitamin D with calcium citrate when necessary to control PTH, aggressive screening and treatment of iron deficiency, particularly in menstruating women, and zinc replacement paired with copper due to competitive absorption are among the specific recommendations. To identify and treat deficiencies early and reduce risks including neuropathy, osteoporosis, anemia, and metabolic problems, routine laboratory monitoring is necessary (three times in the first year, then one or two times a year for the rest of one’s life).

Takeaway: Monitoring & Adaptation

Although bariatric surgeries can provide long-term health advantages, drug safety is a crucial aspect of long-term therapy due to physiological changes, and these must be considered when determining if treatment is appropriate for the patient. Certain medications, such as lithium, lipophilic medications, oral contraceptives, etc., require closer monitoring or alternate therapies since drug absorption, distribution, and clearance may differ significantly following surgery. In addition, maintaining general metabolic health and preventing continual micronutrient deficits need lifelong nutritional monitoring. Clinicians and patients can collaborate to maximize therapy, avoid toxicity, and ensure the positive outcomes of surgery are matched with safe and efficient medication administration by understanding how these procedures alter both nutrients and drug treatments.

Lauren T., APPE Student

References

1. Ayub S, Saboor S, Usmani S, Javed S, Tonpouwo GK, Ahmed S. Lithium toxicity following Roux-en-Y gastric bypass: Mini review and illustrative case. Ment Health Clin. 2022 Jun 10;12(3):214-218.
2. Alalwan AA, Friedman J, Alfayez O, Hartzema A. Drug absorption in bariatric surgery patients: A narrative review. Health Sci Rep. 2022 Apr 26;5(3):e605. 
3. Chacon D, Bernardino T, Geraghty F, Carrion Rodriguez A, Fiani B, Chadhaury A, Pierre-Louis M. Bariatric Surgery With Roux-En-Y Gastric Bypass or Sleeve Gastrectomy for Treatment of Obesity and Comorbidities: Current Evidence and Practice. Cureus. 2022 Jun 8;14(6):e25762.
4. Delaye, Matthieu et al. Management of Pain Medication in Patients With a History of Bariatric Surgery: A Systematic Review. Journal of Pain and Symptom Management, Volume 67, Issue 6, e859 – e868
5. D. Quilliot, M. Coupaye, C. Ciangura, S. Czernichow, A. Sallé, B. Gaborit, M. Alligier, P.-L. Nguyen-Thi, J. Dargent, S. Msika, L. Brunaud, Recommendations for nutritional care after bariatric surgery: Recommendations for best practice and SOFFCO-MM/AFERO/SFNCM/expert consensus, Journal of Visceral Surgery, Volume 158, Issue 1, 2021, Pages 51-61.
6. Heeyoung Lee, Brayden Kameg, Josua Palmer, Alice C. Cline, Pharmacokinetic Changes in Medications After Bariatric Surgery: A Scoping Review, The Journal for Nurse Practitioners, Volume 20, Issue 7, 2024.
7. Kingma JS, Burgers DMT, Monpellier VM, et al. Oral drug dosing following bariatric surgery: General concepts and specific dosing advice. Br J Clin Pharmacol. 2021; 87(12): 4560–4576.
8. Konstantinidou SK, Argyrakopoulou G, Dalamaga M, Kokkinos A. The Effects of Bariatric Surgery on Pharmacokinetics of Drugs: A Review of Current Evidence. Curr Nutr Rep. 2023 Dec;12(4):695-708. Epub 2023 Oct 20. 
9. Michael A. Edwards, Kinga Powers, R. Wesley Vosburg, Randal Zhou, Andrea Stroud, Nabeel R. Obeid, John Pilcher, Shauna Levy, Karina McArthur, Givi Basishvili, Amy Rosenbluth, Anthony Petrick, Henry Lin, Tammy Kindel, American Society for Metabolic and Bariatric Surgery: postoperative care pathway guidelines for Roux-en-Y gastric bypass, Surgery for Obesity and Related Diseases, Volume 21, Issue 5, 2025, Pages 523-536.
10. Mitchell BG, Collier SA, Gupta N. Roux-en-Y Gastric Bypass. [Updated 2024 Nov 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553157/
11. Porat D, Dahan A. Pharmacokinetics after bariatric surgery: adverse effects and drug safety issues in bariatric patients. Expert Rev Clin Pharmacol. 2025 Mar;18(3):101-108. Epub 2025 Feb 7. 

Overview

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It is currently marketed under three different brand names: Ozempic®, Wegovy®, and Rybelsus®. With actions of lowering blood sugar, reducing the risk of cardiovascular disease, and suppressing appetite to facilitate weight loss, some may wonder, is this medication a solve all? Not all brand names of semaglutide have the same indications with the FDA nor the same formulations, and access due to cost differs between them. The right semaglutide formulation needs to be chosen with a full understanding of these differences to ensure the therapy selected will match the specific clinical needs of the patient and also align with the capabilities of the patient for ease of adherence to dosing instructions. With the growing patient and physician preference for GLP-1s, it is worth asking, when should it be used?

How Do Semaglutide Medications Differ?

While Ozempic, Wegovy, and Rybelsus contain the same active ingredient, their clinical characteristics differ. To better understand these differences, below are some informational tables that point out their differences with regards to their storage, dosage, FDA-approved Indications, and dosing schedules.

Choosing the Right Semaglutide for a Patient

Selecting the appropriate semaglutide product depends on the patient’s indication, preferred route of administration, comorbidities, and ability to adhere to required dosing instructions. For example, Rybelsus® is appropriate for patients who prefer an oral option and are willing to follow strict administration requirements (e.g. empty stomach).

Adverse Effects & Safety

Adverse Effects

• Gastrointestinal: The most common adverse effects of GLP-1RA therapies are gastrointestinal which include nausea, vomiting, constipation, diarrhea, and abdominal pain. In addition, decreased appetite, dysgeusia, and dyspepsia have also been reported. The majority of GLP-1RA treatment regimens reported nausea as the most frequent gastrointestinal side effect, particularly when beginning a GLP-1 or shortly following dose. To mitigate this, meal portioning can help lower the chance of this adverse effect. 

• Hypoglycemia: GLP-1 agonists can result in hypoglycemia by lowering blood glucose. When semaglutide is taken with other anti-hyperglycemic drugs such insulin, metformin, or sulfonylureas, the risk of hypoglycemia increases considerably. 

• Renal: Incidences of acute kidney injury more likely to occur in patients who had nausea, vomiting, diarrhea, or dehydration during therapy. It has been suspected to be linked with volume depletion or insufficient hydration.

• Gallbladder disorders: Semaglutide has been linked to biliary tract and gallbladder problems, such as cholecystitis and cholelithiasis. The mechanism is unclear exactly how this adverse effect occurs. 

• Risk of thyroid C-cell tumors: Animal trials using semaglutide during the early stages of drug development showed a risk of thyroid C-cell tumors. However, it is currently unknown whether semaglutide and thyroid malignancies in humans are related. People who have been diagnosed with multiple endocrine neoplasia type 2 (MEN2) syndrome or who have a personal or family history of medullary thyroid carcinoma (MTC) may be at higher risk.Other adverse reactions: Fatigue, headache, soreness at the injection site, and erythema at the injection site.

• Other adverse reactions: Fatigue, headache, soreness at the injection site, and erythema at the injection site.

Precautions/Warnings/Contraindications

• Semaglutide may affect the absorption of concurrently given oral drugs since it delays the emptying of the stomach. In research, semaglutide had no clinically significant impact on the absorption of drugs taken orally. However, when taking oral drugs along with semaglutide, caution should be used.

• To minimize the risk of transmitting infectious diseases, individuals shouldn’t share the multiple-dose injectable pen (Ozempic®).

• When using semaglutide, patients with a history of bariatric surgery are more likely to experience gastrointestinal issues. Regular monitoring in these individuals is recommended.

• Rebound weight gain has been seen with the discontinuation of GLP-1 RAs. Participants in the STEP 1 trial regained almost two-thirds of their original weight loss after stopping weekly subcutaneous semaglutide (Wegovy®) 2.4 mg and lifestyle modifications for a year.

• GLP-1 RAs are contraindicated with personal or family history of MTC or in patients with MEN2. Semaglutide is also contraindicated in patients with type 1 diabetes.

Cost Barriers

Insurance plans differ in their coverage of weight-loss drugs. Wegovy® and other prescription drugs used just for weight loss may not be covered by many insurance companies, or they may need prior authorization. Many individuals pay out of pocket monthly using manufacturer coupons, but paying high costs long-term may not be attainable. FDA-approved GLP-1 RAs such as Ozempic® and Rybelsus® may be covered by your insurance if you have T2DM.

Overall, semaglutide is available as Ozempic®, Wegovy®, and Rybelsus®, each designed for different therapeutic goals and delivered through distinct dosage forms and dosing schedules. Selecting the right formulation requires aligning the product with a patient’s clinical needs, preferred route of administration, and ability to adhere to specific instructions. While semaglutide offers significant benefits for diabetes, weight management, and cardiovascular health, it also carries important safety considerations and potential side effects that must be addressed prior to initiation. In addition, access and coverage can vary significantly, making these important factors in choosing the most appropriate therapy.

Lauren T., APPE Student

References

1. Calvarysky B, Dotan I, Shepshelovich D, Leader A, Cohen TD. Drug-Drug Interactions Between Glucagon-Like Peptide 1 Receptor Agonists and Oral Medications: A Systematic Review. Drug Saf. 2024 May;47(5):439-451.
2. Jialal I, Olatunbosun ST. Oral Semaglutide Therapy Reduces Cardiovascular Events in Patients with Type 2 Diabetes: Deciphering the Soul of the Study. J Clin Med. 2025 May 11;14(10):3335. 
3. Kommu S, Whitfield P. Semaglutide. [Updated 2024 Feb 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK603723/
4. Petralli, G., Zoppo, A.D., Rovera, C. et al. Different formulations of semaglutide and oxidative stress in subjects with type 2 diabetes and MASLD: an open-label, real-life study. Acta Diabetol 62, 1429–1437 (2025). 
5. Ryan DH, Lingvay I, Deanfield J, Kahn SE, Barros E, Burguera B, Colhoun HM, Cercato C, Dicker D, Horn DB, Hovingh GK, Jeppesen OK, Kokkinos A, Lincoff AM, Meyhöfer SM, Oral TK, Plutzky J, van Beek AP, Wilding JPH, Kushner RF. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med. 2024 Jul;30(7):2049-2057.
6. Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Rosenstock J, Wadden TA, Wharton S, Yokote K, Kushner RF; STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564. 
7. Xie X, Yang S, Deng S, Liu Y, Xu Z, He B. Comparative gastrointestinal adverse effects of GLP-1 receptor agonists and multi-target analogs in type 2 diabetes: a Bayesian network meta-analysis. Front Pharmacol. 2025 Sep 19;16:1613610.

Overview

CKD is a life limiting diagnosis, and as kidney function declines, it can be the result of terminal illness. All of which to say, CKD is preventable, and the treatment regimen often targets the combination of factors that cause it, specifically HTN and T2DM. Clinical trials have shown that mineralocorticoid receptor antagonists, glucagon-like peptide 1 receptor agonists, and sodium-glucose co-transporter 2 inhibitors are beneficial in lowering adverse events in CKD, significantly increasing the options for effective treatment. These drug classes have been suggested as the four pillars of CKD, together with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. However, even in high-risk individuals, these medications are underutilized for therapy management.

Chronic Kidney Disease and its Intersection with Risk Factors

• T2DM is the primary leading cause of CKD and can serve as a predictor for kidney disease progression. Antiglycemic agents are an essential approach for lowering the risk of kidney disease irrespective of T2DM diagnosis. 

• Chronic hypertension is the second leading cause for CKD because it results in the long term increase of glomerular pressure which can damage the renal vasculature leading to the acceleration of kidney disease progression. Even mild blood pressure elevations can increase the risk of developing CKD and progressing toward ESRD. Blood pressure management in CKD patients should be considered irrespective of hypertension.
  • Per 2024 KDIGO guidelines, a standardized blood pressure of less than 120/80 mmHg is advised to lower the risk of cardiovascular disease and the onset and progression of chronic kidney disease. However, blood pressure targets should be customized based on life expectancy, frailty, and fall and fracture risk.

• AKI is becoming more widely acknowledged as a precursor to CKD. The vulnerable 7 to 90 day period following AKI when kidney function has not fully restored is known as AKD. During this timeframe, patients are at higher risk of transitioning to CKD, ESRD, cardiovascular complications, and mortality. Close monitoring is needed to ensure no further kidney damage occurs during AKD.

• T2DM, HTN, and AKI are all factors that contribute to CVD and strong indicators of CKD. As we dive into the treatment and management of CKD, it is important to recognize that optimization of these drug therapies for these indicators alone would serve as a preventative. 

Overall Prevalence in the Adult General Population

• Women are slightly more likely than men to have CKD (14.4% versus 11.8%)
• CKD affects about 20% of non-Hispanic Black adults
• CKD affects about 12% of non-Hispanic White adults
• CKD affects about 14% of non-Hispanic Asian adults
• CKD affects about 14% of Hispanic adults
• People 65 years of age or older had the highest prevalence of CKD (33.7%), followed by those 45 to 64 (12.3%), and those 18 to 44 (6.3%)

CKD: Trends in Adults with T2DM & HTN

The following charts and data below take a look at trends with respect to population and various disease states:

Source and Images: Centers for Disease Control. Available at: https://wwwn.cdc.gov/kdss/TopicHome/PrevalenceIncidence.aspx?topic=1

Without adjusting for age, sex, or other demographics (⋯ overall), the prevalence was 12.9% in 2001-2004 and 13.9% in 2017-2020. CKD was more common in women, individuals 70 years of age or older, non-Hispanic Black adults, and adults with diabetes or hypertension.

Albuminuria: Trends in Adults with T2DM & HTN

Source and Images: Centers for Disease Control. Available at: https://wwwn.cdc.gov/kdss/TopicHome/PrevalenceIncidence.aspx?topic=1

Without adjusting for age, sex, or other demographics (⋯ overall), the prevalence was 9.4% in 2001-2004 and 10.2% in 2017-2020. Albuminuria was more common in women, individuals 70 years of age or older, non-Hispanic Black adults, adults with diabetes, hypertension, and CKD Stages 4 and 5.

Note: UACR (measure of kidney damage) and eGFR (measure of renal function) are the two primary indicators of kidney disease that should be checked at least once a year in those with or at risk of CKD. The KDIGO 2024 guideline recommends repeat testing three months after the identification of an abnormal eGFR or UACR.

What are the Four Core Pillars of CKD?

RAS Inhibitors: Reduce Kidney Failure Risk

• When compared to placebo or other antihypertensive medications, ACEis or ARBs decreased the incidence of kidney failure requiring renal replacement therapy in individuals with CKD.

SGLT2 Inhibitors: Reduced CKD Progression Risk

• SGLT2 inhibitors are known to be effective in diabetes management, but studies are beginning to show that the benefits extend beyond blood glucose control. When compared to a placebo, treatment groups with SGLT2 inhibitor therapy had a 37% lower risk of kidney disease progression.

nsMRA (finerenone): Combination Therapy for UACR Reduction

• The 2024 KDIGO guidelines recommend combining finerenone with SGLT2 and RAS inhibitors. Finerenone has been demonstrated to lower composite kidney outcomes, heart failure hospitalizations, and all-cause mortality in those with CKD and T2DM. 

• The CONFIDENCE trial showed that starting empagliflozin and finerenone together resulted in significantly greater albuminuria reductions than either medication alone.
  • Combination therapy: Reduced UACR from baseline by 52%
  • Monotherapies: Finerenone or empagliflozin reduced UACR by 32% and 29%, respectively.

GLP-1 RA: Reduction in Kidney Composite Outcomes

• According to the 2024 KDIGO guidelines, individuals with T2DM and CKD who are unable to utilize metformin and a SGLT2 inhibitor or who do not achieve glycemic targets with both medications should also use a GLP-1 receptor agonist. 

• GLP-1 RAs reduce kidney composite outcomes by 21%.

The Bottom Line in CKD Management

CKD management involves a proactive and comprehensive treatment approach as incidence continues to rise. RAS inhibitors, SGLT2 inhibitors, nsMRAs, and GLP-1 RAs are the core pillars. This is a significant change in the way medical professionals manage kidney health. Blood pressure and glucose control are no longer the only ways to manage CKD; instead, these treatments are combined to delay the disease course, lower cardiovascular risk, and greatly improve long-term outcomes.

The four therapies are changing the standard of care with updated KDIGO recommendations and new evidence in support of combination therapy. In addition to refining medication regimens, pharmacists and other healthcare providers must stay up to date on these new medications in order to educate patients, detect care gaps, and promote timely screening with eGFR and UACR.

Ultimately, the best chance of influencing the course of CKD and improving quality of life for many individuals at risk is through early intervention, guideline-driven therapy, and coordinated care.

Lauren T., APPE Student

References

1. Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A, Filippatos G; FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Dec 3;383(23):2219-2229. Epub 2020 Oct 23. 
2. Burnier, Michel and Damianaki, Aikaterini. Hypertension as Cardiovascular Risk Factor in Chronic Kidney Disease. Circulation Research, vol. 132, no. 8, 2023, pp 1050-1063. 
3. Cheng, A.Y.Y., Mottl, A. & Magwire, M. Pillar Risk-Based Treatment for Chronic Kidney Disease in People With Type 2 Diabetes: A Narrative Review. Diabetes Ther 16, 2083–2099 (2025).
4. Joana Gameiro, Beatriz Gouveia, José Agapito Fonseca, José António Lopes, The burden of acute kidney disease: an epidemiological review and importance of follow-up care, Clinical Kidney Journal, Volume 18, Issue 6, June 2025   
5. Kidney Disease Statistics for the United States – NIDDK. National Institute of Diabetes and Digestive and Kidney Diseases, U.S. Department of Health and Human Services, Sept. 2024, www.niddk.nih.gov/health-information/health-statistics/kidney-disease.  
6. Koh ES, Chung S. Recent Update on Acute Kidney Injury-to-Chronic Kidney Disease Transition. Yonsei Med J. 2024 May;65(5):247-256.
7. Treihaft A M, Parikh M A, Jackson K A, et al. (April 07, 2025) New Therapies for the Management of Chronic Kidney Disease. Cureus 17(4): e81824.