More than diabetes and weight management

GLUCAGON-LIKE PEPTIDE-1 (GLP-1) receptor agonists have garnered substantial attention for their role outside the management of type 2 diabetes, including for the treatment of obesity and cardiovascular disease. According to Nguyen and Marsh, prescriptions for weight loss drugs, including GLP-1s, more than doubled in 2024 despite poor insurance coverage and high out-of-pocket costs. Truveta estimated that in 2025, GLP-1 prescriptions accounted for 6.5% of all prescriptions in the United States. McGough and colleagues found that over 40% of adults under 65 with private insurance could qualify for a GLP-1 drug under previous Food and Drug Administration (FDA) indications accounting for obesity and type 2 diabetes.

With FDA coverage for chronic kidney disease, obstructive sleep apnea, metabolic-associated liver disease, and cardiovascular diseases, the percentage of people who might benefit from a GLP-1 continues to expand. In addition to studying the long-term safety and efficacy of these medications, ongoing studies are exploring emerging evidence linking their use to a host of other positive outcomes. (See History and context.)

The surprising positive outcomes of GLP-1 therapy observed in many disease processes are attributed to the drug’s mechanism of action, secondary benefits of controlled disease processes, or disease prevention. Disease prevention serves as a major contributor to the positive public health potential of widespread GLP-1 adoption.

Public health impact

According to the Centers for Disease Control and Prevention (CDC), in 2023, 40.1 million people (one in eight) had diabetes; one in four didn’t know they had it. For prediabetes, those figures increase to 115.2 million people, and more than 80% are unaware or undiagnosed. In addition, the CDC confirmed diabetes as the seventh leading cause of death.

Obesity and health

Adipose tissue is not an inert storage for lipids. It functions as an endocrine organ, secreting hormones that facilitate obesity and create a positive feedback loop of hormonal disruption. Being overweight or obese is far more than a cosmetic concern. Obesity, defined as a body mass index (BMI) of ≥30, is a major public health issue with significant economic and societal impacts. Jones and Brierley describe obesity as a chronic, relapsing, and progressive disease. In 2026, the National Health and Nutrition Examination Survey released results, using 2023 data, that demonstrate a historic leveling off of U.S. adult obesity prevalence rates from a previous peak of 42.4% to the current pooled adult prevalence rate of 40.3%. Increasing GLP-1 adoption may play a role in these trends. Concurrently, however, the survey showed that for the first time more than one in five children and adolescents (21.1%) have obesity. Severe obesity (BMI >40) affects nearly 1 in 10 U.S. adults (9.7%).

Individuals with obesity, compared to those with a healthy weight, have increased risk for several serious diseases and conditions, including hypertension, asthma, heart disease, stroke, type 2 diabetes, many cancers, breathing difficulty, and joint issues. According to 2026 CDC statistics, 90% of healthcare spending in the United States ($441 trillion) goes to chronic conditions; obesity serves as a primary driver of the most expensive chronic conditions (diabetes, heart disease, and cancer).

Affordability and accessibility

GLP-1 medications remain significantly more expensive in the United States compared to any other developed country. Barriers persisted in efforts to decrease the U.S. out-of-pocket costs for the medications from over $1,000 before insurance and savings cards, to the <$150 average prices paid in European countries. In 2022, the Inflation Reduction Act gave the government the power to lower drug pricing by authorizing the Department of Health and Human Services to negotiate prices directly with manufacturers. Two GLP-1 agents appeared in the second round of price negotiations in 2024–2025. For patients receiving Medicare, the negotiated 30-day supply rates for those agents fell from $959 to $274. These changes are scheduled to go into effect in 2027.

In late 2024, as discussed by Amin and colleagues, the Peterson-Kaiser Family Foundation released information gathered from the Organisation for Economic Co-operation and Development data of global GLP-1 pricing. In the United States, monthly pricing was over $900 USD compared to $83 USD per month for semaglutide in France and $103 USD per month in Germany. Even in complex access environments, such as the United States, where preventive care isn’t the standard, decision-making with regard to GLP-1 use and coverage requires long-term benefit analysis of disease states. Health insurance companies and employers, who pay initial upfront costs, don’t typically see the long-term benefits patients experience with these medications.

The lack of affordable, accessible GLP-1 medications will continue to obfuscate future large cohort analysis of patients using them due to the disrupting influences of social determinants of health. The populations that lack access to these medications tend to be those that could benefit most from them.

GLP-1 opposition

Opponents of GLP-1 therapy chastise its use for cosmetic weight loss. Some extreme viewpoints question whether medication should ever be used for weight management if diet and exercise can be effective.

However, most obesity specialists agree that obesity is a multifaceted disease that can involve genetic predisposition and dysfunction of certain hormones, including ghrelin (a hunger hormone) and leptin (a satiety hormone).

Indications and mechanism of action

As described by Liu, GLP-1 pathophysiology involves multiple mechanisms of action that improve glucose control and promote weight loss, including enhanced insulin secretion, inhibited glucagon release, delayed gastric emptying, increased satiety, and improved insulin sensitivity. According to Liu, compared to other antidiabetic medications, GLP-1s more effectively improve glycemic control in patients with type 2 diabetes, with reduced risk of hypoglycemia. Liu also notes that on average, GLP-1 medications can lower A1C by 0.78% to 1.9%. According to Horn and colleagues and Milushewa and colleagues, factors such as initial A1C level, adherence to medication, and other underlying health conditions can influence actual A1C reduction.

According to Jones and Brierley, GLP-1s also influence the central nervous system, particularly in the regulation of appetite, satiety, and food intake. The brain regions involved include the hypothalamus, hippocampus, and brainstem, which express GLP-1 receptors. The medication acts on corresponding receptors in the central nervous system to modulate appetite and energy homeostasis. In the hypothalamus, GLP-1 promotes satiety and reduces hunger signals. These are important mechanisms of action to consider when evaluating the effects of decreased alcohol, tobacco, and other substance use that’s been noted with GLP-1s. Emerging research, including from Zhang and colleagues, Tang and colleagues, and He and colleagues, also notes neuroprotective, cognitive-enhancing, and psychiatric-modulating potential.

Tirzepatide, a single molecule, acts as a dual agonist, targeting GLP-1 and gastric inhibitory peptide (GIP) receptors. L cells in the lower small intestine and colon excrete GIP, an incretin hormone, in response to fatty acids and glucose.

In addition to stimulating insulin secretion from the pancreas, GIP also may play a role in fat storage and memory formation. In 2023, the FDA approved tirzepatide for obesity, which, according to Gratzl and colleagues, contributed to an increase in prescribing trends of GLP-1 medications. (See GLP-1 research.)

The combined effects of these mechanisms of action make GLP-1 an effective treatment for type 2 diabetes and obesity, with ongoing studies exploring its broader therapeutic potential. Because the GLP-1 and GIP receptors are present throughout the body, GLP-1 therapy can have anti-inflammatory effects on multiple tissues. For example, GLP-1s offer cardioprotective effects, likely mediated by improved endothelial function and reduced inflammation.

Current understanding of the pathophysiology and mechanisms of action of GLP-1 medications remains incomplete, but ongoing research continues to improve that understanding and has led to the discovery of other disease states that may benefit from GLP-1 supplementation.

Side effects

Most individuals can tolerate GLP-1s, but the medications can have adverse effects and side effects. Side effects are generally predictable and usually less serious than adverse effects, which encompass all undesirable outcomes of a medication or treatment, including serious reactions.

In GLP-1s, both adverse effects and side effects primarily stem from their mechanisms of action, impacting multiple physiological systems, including the GI tract, pancreas, and central nervous system. Understanding the causes provides insight into why they occur and how they might be managed.

GI side effects, the most reported, include nausea, vomiting, constipation, and diarrhea. Typically, these symptoms are dose-dependent and diminish as the body adapts to the medication over time. In trials by Xie and colleagues, 47% to 84% of participants reported GI disturbances, similar to real-world use observations. GLP-1 slows gastric emptying, which prolongs the time food remains in the stomach. This can lead to feelings of fullness, bloating, and discomfort, particularly after meals. Slow gastric emptying may serve as a major contributor to nausea and vomiting.

GLP-1s also act on the central nervous system, particularly the brainstem and hypothalamus, where it regulates satiety and appetite. This can trigger nausea and vomiting as the body adjusts to changes in hunger and fullness signals.

As GLP-1s enhance gut motility and enzyme secretion, some patients may experience diarrhea. However, according to Aldhalei and colleagues, about a third of GLP-1 users experience constipation. Severe constipation can occur secondary to decreased fluid intake. Research by Su and colleagues suggests that genetic variations influence how individuals respond to GLP-1 medications in terms of both weight loss and side effects. In addition to directly impacting gut motility on a pharmacologic basis, GLP-1s are used to modify behavioral food and fluid patterns. Skipping meals, meal timing, portion size, intake speed, nutritional make up, and fluid ingestion patterns are all potential side effect modifiers. Effective counseling on behavioral modifications can substantially alter the side effect profile. Starting with lower doses and titrating upward slowly reduces the risk of nausea and other GI effects.

Although GLP-1s primarily stimulate insulin secretion in a glucose-dependent manner (for instance, only in the presence of elevated blood glucose), hypoglycemia can still occur in certain situations such as insufficient food intake, excessive exercise, and particularly when used in combination with other antidiabetic agents, such as sulfonylureas or insulin. Nurses can explain that GLP-1 medications are “smart” about when the body releases insulin. In general, unlike insulin and sulfonylureas, which lower blood sugar regardless of whether it’s currently high or normal, GLP-1s carry a very low risk of hypoglycemia because they only tell the body to release insulin when blood sugar levels are actually high. However, the compounded effect of adding a GLP-1 to a patient’s regimen that already includes insulin or a sulfonylurea can push their blood sugar too low. When initiating GLP-1 therapy in conjunction with insulin or a sulfonylurea, providers may consider proactive dose reductions of those agents to avoid potential hypoglycemia.

Serious GLP-1 adverse effects remain rare. GLP-1s should be used cautiously in patients with a history of pancreatitis, but it’s not a contraindication. Case reports described by Drucker and colleagues link GLP-1 use to acute pancreatitis, although a direct cause-and-effect relationship hasn’t been definitively established. In addition, according to the Xie and colleagues, a theoretical risk of thyroid C-cell tumors exists, based on rodent studies; however, this hasn’t been demonstrated in humans.

Reports by Wileman and colleagues suggest a potential link between GLP-1s and renal complications, such as acute kidney injury, but these are rare and thought to result from dehydration caused by GI side effects. Severe nausea, vomiting, and diarrhea can lead to dehydration, which, in turn, may result in kidney dysfunction. These effects are more common as the body adjusts to the medication, such as when initiating a GLP-1 or when escalating doses too quickly. According to Perkovic and colleagues, outside of dehydration, GLP-1 medications are nephroprotective, as suggested by semaglutide’s 2025 indication for chronic kidney disease, because of its ability to limit kidney damage.

GLP-1 side effects are primarily driven by the drug’s effect on gastric emptying, insulin secretion, and appetite regulation. Although hypoglycemia, pancreatitis, and potential thyroid cancer are less common, they require close monitoring, particularly in patients with other risk factors. Proper patient selection, dose titration, and monitoring can help mitigate many side effects. Ongoing patient surveillance and risk-benefit assessments are essential for clinical use of traditional GLP-1s. As new evidence emerges comparing oral GLP-1 medications with injectable forms, close monitoring and shared decision-making should remain consistent.

Emerging evidence and recent advances

Evidence continues to emerge regarding additional indications and benefits of GLP-1 medications, including effects on aging, dementia, Parkinsonism, wound healing, knee arthritis pain, auto-immune conditions, substance use, cancer prevention, and cardiac health.

Anti-aging

Studies by Nagae and colleagues and Chen and colleagues suggest that GLP-1s can stimulate autophagy, a natural cellular process that breaks down cells and recycles damaged components. By removing damaged cellular components, autophagy helps maintain cellular function and prevent age-related decline. For example, autophagy plays a crucial role in brain health; GLP-1–induced autophagy may contribute to neuroprotection, helping to prevent or slow age-related cognitive decline.

GLP-1s also may promote apoptosis (a natural process that helps eliminate damaged or unhealthy cells) in certain types of cells, such as cancer cells, and inhibit it in healthy cells, promoting cell survival. However, the interactions between GLP-1s, autophagy, and apoptosis are complex and not fully understood.

GLP-1s also improve metabolic health by regulating blood sugar, reducing insulin resistance, and lowering cholesterol levels. These factors, crucial for healthy aging, reduce the risk of age-related diseases like type 2 diabetes, heart disease, and stroke. In addition, the anti-inflammatory properties of GLP-1s may play a role in protecting against stress and age-related diseases.

Dementia

Recent research suggests a potential link between GLP-1s and a reduced dementia risk. Observational studies by AbuAlrob and colleagues indicate an association between GLP-1s and a lower risk of dementia in patients with diabetes compared to those taking other diabetes medications. A 2023 register-based study by Tang and colleagues followed 88,000 older adults with type 2 diabetes for 10 years and observed a 30% lower risk of dementia compared to those taking sulfonylureas. The exact mechanisms underlying this potential association aren’t fully understood, but potential hypotheses include reduced inflammation and neuroprotective effects.

Parkinsonism

GLP-1s may have a disease-modifying effect in the development and progression of Parkinson’s disease (PD), but Gandhi and colleagues have so far yielded inconsistent results. Preclinical studies by Lv and colleagues have shown that GLP-1s can restore dopamine levels, inhibit dopaminergic loss, attenuate neuronal degeneration, and alleviate motor and non-motor features of PD. A clinical trial by Meissner and colleagues with the GLP-1 lixisenatide demonstrated a modest reduction in motor disability progression in patients with early-stage PD. In addition, among Medicare beneficiaries with type 2 diabetes, the use of GLP-1s has been significantly associated with a decreased risk of PD.

Wound healing and amputation

The multifaceted effects of GLP-1s on wound healing include disease prevention, disease amelioration, and direct wound impact. Diabetes, obesity, peripheral arterial disease, cancer, and substance use can impact both the incidence of wounds as well as the wound healing process. For example, according to Swoboda and Held, the mechanisms of delayed wound healing in diabetes can involve a perfect storm of vascular, cellular, and biochemical disruptions. These factors prevent the wound from progressing through the normal stages of healing (hemostasis, inflammation, proliferation, and remodeling), frequently trapping the tissue in a state of chronic inflammation. GLP-1 medications facilitate improved wound healing in patients with diabetes by mitigating chronic inflammation, enhancing skin cell proliferation and migration, and promoting angiogenesis, thereby addressing the underlying vascular and cellular impairments characteristic of diabetic ulcers.

According to Xuan and colleagues and Buranasin and colleagues, in patients with diabetes, GLP-1s maintain glucose homeostasis to promote healing; however, the medications’ benefits also may help individuals who don’t have diabetes. Emerging research, including from He and colleagues and Patel and colleages, suggests a potential positive association between GLP-1s and wound healing, which involves intricate biocellular mechanisms that rely on autophagy and apoptosis.

For example, GLP-1s can improve blood circulation, essential for delivering nutrients and oxygen to a wound site. According to Bonaca and colleagues, improved blood flow translates to enhanced quality of life, demonstrated by the 2025 results of the STRIDE trial, in which semaglutide significantly increased walking distance and improved function in patients with peripheral arterial disease and type 2 diabetes. GLP-1s’ anti-inflammatory effects may aid in regulating inflammation at a wound site and promote healing.

In addition, GLP-1s may enhance cell growth and the proliferation of cells associated with wound healing, such as fibroblasts and keratinocytes. Although promising, current research remains limited; more clinical trials are needed to investigate the relationship between GLP-1s and wound healing in humans. According to Krajewski and colleagues and Haran and colleagues, GLP-1 medications have been reported to exert positive clinical impact on other inflammatory skin disorders that commonly lead to wounds such as hidradenitis suppurativa and psoriasis.

Further definitive research with a primary focus on amputation prevention is needed; however, current research, as noted by Werkman and colleagues, indicates that GLP-1s may help reduce the risk of lower extremity amputation in patients with type 2 diabetes.

Knee arthritis pain

Osteoarthritis, the most common form of arthritis according to the CDC, causes significant pain and functional limitations. Research indicates that GLP-1s may have beneficial effects in those with knee osteoarthritis, including reduced pain and fewer joint replacements by reducing weight and inflammation. A study by Messier and colleagues found an association between GLP-1 use and decreased incidence of knee surgery. Bliddal and colleagues reported that patients taking GLP-1s described control of their knee osteoarthritis pain on par with narcotic pain medication.

According to Fu and colleagues, antidiabetic drugs may play a therapeutic role in treating osteoarthritis. For every pound of weight lost, patients experience a substantial decrease with each step in the force placed on weight-bearing joints such as the knees and hips. This reduced force translates to less stress and wear and tear on the cartilage and surrounding tissues within the joints. A common estimate suggests that for every pound of body weight, the knees experience the force of 3 pounds of pressure with each step taken. Losing just 10 pounds would result in a 30-pound decrease in pressure on knees for every step.

Despite the prevalence of osteoarthritis, no disease-modifying treatments exist. Instead, care primarily focuses on ameliorating symptoms rather than halting or reversing disease progression. Metabolic dysregulation plays a role in osteoarthritis pathogenesis. Therefore, in addition to the benefits of general weight loss, antidiabetic medications may have therapeutic potential as disease-modifying agents to halt or reverse osteoarthritis at a cellular level.

Substance use

Current research indicates a link between GLP-1s and reduced incidence and recurrence of alcohol use disorder. A 2024 cohort study by Miller-Matero and colleagues with 14,053 participants found that nearly half of those consuming alcohol at baseline reduced their alcohol intake after starting anti-obesity medications (primarily second-generation GLP-1s). Participants with higher obesity levels or heavier drinking habits were more likely to reduce alcohol use. A 2025 cohort study by Wang and colleagues found that patients on GLP-1s had a 20% to 50% lower risk of developing or relapsing into alcohol use disorder.

Miller-Matero’s large study confirms prior evidence, from Tufvesson-Alm and colleagues, regarding the role of the gut–brain axis in alcohol use. The study also continues the investigation into the suppression of alcohol’s rewarding properties while hinting at wider benefits in other substance use and impulse disorders.

From a public health perspective, harms from drinking increase with consumption, but a large proportion of harm from alcohol consumption occurs in those who don’t drink heavily. According to Rossow, each year in the United States, approximately 20,000 people die from alcohol-attributable cancers, while new cancer cases related to alcohol are approximately 75,000. The risk of some cancers—including breast and those associated with the entire GI tract—increases with any alcohol use. In a 2025 cross-sectional survey, Fokom Domgue and colleagues reported that nearly two-thirds of adults in the United States don’t believe or don’t know that drinking alcohol increases cancer risk.

Alcohol also is associated with many chronic diseases, including high blood pressure, cardiovascular disease, liver disease, stroke, digestive problems, dementia, mental health conditions, and a weakened immune system. The widespread use of GLP-1 medications and expected reductions in substance use has the potential to prevent or limit associated cancers and chronic diseases.

Cancer prevention

In addition to the cancer risks associated with alcohol consumption, the CDC and National Cancer Institute note that being overweight or having obesity also increases the risk of at least 13 cancers, including kidney, ovary, and pancreas. Cancer risk increases with the more excess weight a person gains and the longer they’re overweight. In 2022, the CDC reported that more than 716,000 obesity-associated cancers occurred in the United States. According to Ayesh and colleagues, GLP-1 use significantly reduces the risk of 10 out of 13 obesity-associated cancers primarily by preventing diseases associated with cancer (obesity and alcohol) vs being primarily anti-tumorigenic. The cancers most favorably prevented by GLP-1 use were colon (16% fewer cases) and rectal (28% fewer cases).

Sleep apnea

Zepbound (tirzepatide) is the first and only GLP-1/GIP receptor agonist to receive FDA approval to treat moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity. Obesity is a significant OSA risk factor. The weight loss achieved with GLP-1s indirectly improves OSA symptoms by reducing the fat deposits surrounding the upper airway that contribute to its collapse during sleep. In some cases, if a patient is prescribed a GLP-1 for diabetes or obesity and experiences an improvement in their OSA, this could be considered a positive outcome, even if the drug wasn’t specifically prescribed for the sleep disorder. However, an FDA indication doesn’t guarantee insurance coverage for OSA.

Cardiovascular conditions

In 2024, the CDC reported heart disease as the leading cause of death in the United States. Individuals with type 2 diabetes and obesity face a high risk for developing cardiovascular disease and experiencing major cardiac events or conditions, including myocardial infarction, stroke, heart failure, cardiovascular death, and peripheral arterial disease.

Multiple large outcome trials, such as those conducted by Marso and colleagues and Aronne and colleagues, have shown GLP-1 to exert beneficial cardiovascular effects. GLP-1s provide cardiovascular benefits beyond glycemic control, such as lowering blood pressure, improving endothelial function, and reducing markers of inflammation.

GLP-1s also may lead to decreased free fatty acid concentrations. Fatty acids can irritate the lining of blood vessels, contributing to vascular disease over time. In addition to treating the cardiac stresses that occur with obesity and associated morbidities, such as OSA, additional cardiovascular benefits of GLP-1s are thought to be mediated by their action on vascular smooth muscle cells and endothelial cells. GLP-1s also promote vasodilation by stimulating the release of nitric oxide from endothelial cells.

In the LEADER trial (Marso, Daniels and colleagues), which studied the GLP-1 liraglutide, major cardiovascular events decreased by 13% in patients with type 2 diabetes at high cardiovascular risk. The SUSTAIN trials (Marso, Brian and colleagues) for semaglutide resulted in similar findings. In 2017, liraglutide became the first GLP-1 receptor agonist approved by the FDA to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease, based on results from the LEADER trial. Further approvals included established cardiovascular disease in individuals who are overweight or have obesity as well as those with multiple cardiovascular risk factors. According to Honigber and colleagues, semaglutide and dulaglutide received the same indication in 2020. In 2025, the semaglutide Rybelsus was the first oral GLP-1 to receive the indication. The SELECT trial (Lincoff and colleagues) of semaglutide in overweight or obese adults with established cardiovascular disease but without diabetes found a 20% reduction in major heart events.

At the 2025 Heart Rhythm Society annual meeting, Sundaram and colleagues presented the results of the TRANSFORM-AF trial. The study found that in patients with atrial fibrillation (AF) and obesity, an association existed between the use of GLP-1s and a 13% reduction in major AF-related events, including cardioversions, hospitalizations, and ablation procedures. Karakasis and colleagues’ meta-analysis also found that among individuals with overweight or obesity, an association between GLP-1s and lower risk of an AF event.

Nursing implications

GLP-1 receptor agonists demonstrate considerable promise beyond their established use in treating diabetes and obesity. Emerging research suggests potential benefits in various areas, including cardiovascular health, neuroprotection, substance use, and even cancer prevention. However, the side effects and continued high cost of these medications present significant access barriers, limiting their potential public health impact. Addressing cost-related challenges and expanding research into new indications are crucial steps toward realizing the full potential of GLP-1 receptor agonists.

Nurses serve as the essential clinical anchor in GLP-1 therapy, expertly bridging gaps and ensuring safety through comprehensive screening prior to initiation, dose titration education, and proactive management of side effects. By providing access to effective behavioral counseling, which can substantially alter the GLP-1 side effect profile, nurses can help increase patient adherence and quality of life. Nurses make the optimization of the public health impact of widespread GLP-1 adoption possible by managing therapy outcomes, educating the millions of Americans affected, and facilitating the transition from clinical drug approval to successful long-term disease prevention and management.

Laura Swoboda is chief medical officer at Skin Gurus in Mequon, Wisconsin.

American Nurse Journal. 2026; 21(6). Doi: 10.51256/ANJ062648

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Key words: GLP, semaglutide, tirzepatide, GLP-1RA