If you’ve taken a medication for several months and you still don’t feel well, it might not be the right medication for you.” “If you’re constantly not feeling well, maybe you’re on a dose that’s too high or you’re not on the right medication. A good weekly goal is 150 minutes of moderate-intensity aerobic exercise (like brisk walking or using the elliptical), two to three days of strength training, and some flexibility work (such as yoga). Other forms of exercise are also important for preserving bone density (something else you can lose while taking a GLP-1), reducing abdominal fat, improving heart health, and more. “Muscle function is the health of your muscles and what that means in terms of your ability to be physically active and do all the things you want to do,” she says. GLP-1 drugs work by triggering insulin release, reducing glucose (sugar) production in your liver, and making you feel full.While some patients might afford to pay the total price out of pocket, others might have to prioritize buying the medicines covered by insurance for other health conditions.It’s modern and responsive but less specialized in GLP-1 management.Semaglutide is indicated for weight loss in pediatric patients over the age of 12 with obesity.Some studies suggest the delayed gastric emptying is only in the first hour and overall gastric emptying did not seem to be affected.7,8 GLP-1 is also expressed in the brainstem, endocrine pancreas, and immune system.These drugs work by acting on the brain, so who knows what effect they might have on childhood development and beyond if young people end up taking them for the rest of their lives. One issue that has arisen out of this (and is already being closely watched by state boards of pharmacy and the Institute of Safe Medication Practice, or ISMP) is fraudulent medications that claim to be semaglutide but are actually highly diluted or counterfeit formulations of the drug. Patients may come across health spas and clinics that advertise availability of GLP-1s, but they are generally not certified to dispense medications and have no pharmacy personnel overseeing this dispensing. Because there is a disease process going on, the message to the patient has to be clear that they are committing to these medications for an extended number of years. Most GLP-1 medications are given once weekly, which patients may not be used to as a schedule. A smaller, shorter study reported a lower magnitude of weight loss over 12 weeks (2.1 kg) but with a similar relative contribution of LBM (23.8%) . A third study using DXA, resulted in 2.4 kg weight loss in individuals with T2DM, of which almost 46% was LBM . The most robust evidence of body composition changes with SGLT2i comes from a pair of randomised controlled trials (RCTs) reporting data on the effects of canagliflozin on DXA-derived body composition in individuals with T2DM 40,41. These studies reported a mean weight loss of 2.0 and 2.3 kg, respectively, of which the relative contribution of FFM to total weight loss was 40% and 52% 33,35. Past research also suggests that long-term use of such medications may result in more severe side effects such as hypoglycemia (low blood sugar), pancreatitis, and C-cell hyperplasia, a potential precursor to medullary thyroid carcinoma 7, 11. The particular effect of GLP-1 agonists on weight loss has also made it a popular drug among patients without diabetes. GLP-1 receptor agonists also contribute to glycemic control via a reduction in body weight, which is beneficial for patients with type-2 diabetes . Others are troubled by the harm caused by social media platforms and celebrities heralding medications such as Ozempic® as quick, cosmetic fixes without acknowledging the side effects and the fact that discontinuation results in weight gain. Among the most commonly prescribed drugs for weight management, many are glucagon-like peptide-1 receptor agonists (GLP-1 agonists) which are also utilized for the management of type 2 diabetes. It’s used to treat Type 2 diabetes in adults. If cost is a barrier to accessing treatment, generic Victoza may be an option to consider. One difference between Victoza and most other GLP-1 drugs is that it’s also available as a lower-cost generic. Retatrutide, tirzepatide, and semaglutide—3 glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or coagonists—came out on top of a new investigation that evaluated the efficacy and safety of 12 of the agents for weight loss among adults classified as overweight or obese and who did not have diabetes. They can also evaluate potential interactions with other medications, including those for hypothyroidism or diabetes, and monitor for any adverse effects. Clinical trials should be designed to compare low-dose regimens of GLP-1 treatments to standard full-dose therapies, particularly in the context of managing chronic conditions such as diabetes and obesity. Other obesity management approaches "So keeping the GI tract healthy is essential." "People think constipation is just constipation, but that constipation can turn into intestinal obstruction that can cause perforation and people can die," says Kessler. Remember, the drugs slow down the emptying of the stomach into the small intestine, and that can lead to things getting backed up further down the line, Kessler says. With good medical care, he says, many people can still take pleasure in food at those smaller portion sizes. In clinical trials, adults receiving Wegovy had an average weight loss of nearly 15% of their initial body weight. Researchers have taken interest in how these medications work to not only manage blood sugar, but help people lose weight. The benefits are comparable or superior to the benefits of GLP-1 drugs, including dramatic weight loss and secondary long-term health benefits, such as improved blood sugar levels. If you cannot access or afford newer GLP-1 medications, a generation of older weight loss drugs is still available. GLP-1 drugs can also create a risk of hypoglycemia, or dangerously low blood sugar, in people who use certain type 2 diabetes drugs, chiefly insulin and sulfonylureas. GLP-1 medications are usually injected, but some oral formulations exist. However, the relationship between dose and weight loss is not always linear. This suggests activating multiple receptors may boost weight loss beyond simply increasing the dose. When starting, genetics, body mass index (BMI), and insulin resistance affect how well you will lose weight on a given dose. This health trend is going viral and quickly gaining traction among followers eager for solutions to help them lose weight. “Wraparound care”—an approach to health care that includes mental health, social services, and lifestyle change support—is critical for ensuring success while on a GLP-1. Although more research is needed to determine whether these savings can offset the upfront cost of these drugs, the trend lines appear positive, said Zvenyach. Although none of the panelists could predict what the cost of these drugs would be over the next year, they agreed that the status quo for GLP-1 prices will be changing—soon. Jeffrey Singer of the Cato Institute also proposed that making these drugs available without a prescription might reduce cost, increase access, and decrease stigma, but this change would likely take many years and receive pushback from clinicians. GLP-1 medications can be a powerful tool for weight loss and blood sugar control, but they aren’t right for everyone. Most patients on GLP-1s see significant weight loss, often 15% of their body weight when combined with healthy eating and lifestyle changes. GLP-1 medications are designed to mimic this hormone, which is why they’re effective not only for controlling blood sugar but also for promoting weight loss. “In an ideal world, you would have insurers comparing the burden of covering GLP-1s to the burden of paying for all the other challenges related to long-term chronic disease management. Federal insurers like TRICARE and Medicaid also cover some obesity treatments, and Medicare is currently working to overcome a regulatory barrier to covering GLP-1s. “We need to acknowledge the complexity of the disease of obesity and the complexity of well-managed care, and that the relationship between the two is key.” – Tracy Zvenyach A person taking Wegovy is likely to lose approximately 12% of their body weight, on average, but if they abruptly stop taking the drug, they will likely regain 2/3 of that weight. The chronic nature of obesity becomes evident when people discontinue use of GLP-1s. Although, in the last 10 years, the use of GLP-1 RAs, especially semaglutide and liraglutide, has increased, its clinical implications and how it affects metabolic parameters have yet to be fully consolidated. Although patients will likely continue to request GLP-1 agonists and other weight-loss remedies, we do not have to embrace a weight-centric approach. We must also empathize with patients experiencing weight-based marginalization. These medications are expensive (price), and injections are more complex than oral medications (simplicity). As with all shared decisions, we can start by providing objective information and using a STEPS approach, which outlines a medication's safety, tolerability, effectiveness, price, and simplicity.16 For example, the long-term effects of GLP-1 agonists on the pancreas are unknown (safety). Not everybody responds equally well to these treatments, and it’s impossible to predict how effective any specific weight loss medication will be for you. Wegovy, Zepbound, and Saxenda are all approved as weight loss medications for the following people with a demonstrated medical need to lose weight. Clinical research and studies uniformly demonstrate their ability to contribute to notable weight loss, improve lipid profiles, lower blood pressure, and reduce cardiovascular risk. In a study with 39 participants (BMI ≥ 30 kg/m2), GLP-1RAs such as semaglutide and liraglutide, combined with standard weight management, led to significant weight loss and fewer headache days compared to controls, with lower acetazolamide doses . The only way to guarantee you receive a genuine GLP-1 medicine is to obtain it from a legitimate pharmacy, including those trading online, with a prescription issued by a healthcare professional. GLP-1 medicines should not be bought from unregulated sellers such as beauty salons or via social media, or from anywhere without a prior consultation with a healthcare professional. All GLP-1 medicines are prescription only medicines, which means they can only be prescribed by a healthcare professional. Regardless of how they are classified by any given organization or formulary, I always think of GLP-1s as specialty drugs. With the rise in the awareness of the weight-loss benefits, GLP-1s have become very popular very quickly. The social media frenzy over these drugs helped fuel a 2,082% increase in prescriptions from 2019 to 2022. Exact costs depend on medication type and dosage, but there are no hidden fees or surprise renewals. What’s the difference between semaglutide and tirzepatide? Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for the management of type 2 diabetes, have gained prominence in managing obesity, offering clinically meaningful weight loss of 15–20% in many clinical trials.1 The approval of liraglutide, semaglutide, and tirzepatide for chronic weight management has significantly expanded their use. Beyond glucose control and weight management, GLP-1 drugs have demonstrated potential benefits for cardiovascular health, including reduced risks of heart attacks and strokes in people with diabetes. With that being said, the risks and benefits for those who use the drugs for weight loss would differ from that for people who are using them for the management of diabetes. Participants also had improvement in waist circumference, systolic and diastolic blood pressure, fasting insulin level, lipid levels, and A1c with most of the participants who had prediabetes achieving normoglycemia.2 This demonstrates a significantly decreased 10-year predicted atherosclerotic cardiovascular disease risk.13 Recently, semaglutide was approved for reducing risk of cardiovascular events in patients with cardiovascular disease who are obese or overweight. Perioperative aspiration risk As GLP-1 RAs become more widely used for weight management, attention has turned to their effects on body composition. Early case reports of regurgitation and pulmonary aspiration in patients using GLP-1 RAs raised concerns about their perioperative safety.85 A 2024 scoping review found seven comparative studies reporting higher rates of gastric content retention among GLP-1 RA users (19–56%) vs. non-users (5–20%), though most studies were confounded by comorbidities and varied in methodology.86 In a Mayo Clinic analysis of 4134 GLP-1 RA users undergoing upper endoscopy, only two confirmed aspiration events were identified (4.8 events per 10,000 procedures), closely mirroring a historical rate of 4.6 per 10,000 prior to widespread GLP-1 RA use.87 However, the study acknowledged that not all patients may have been actively using the medication at the time of the procedure, potentially inflating the denominator. While weight loss likely contributes to improvements in some of these conditions, such as liver disease or sleep apnea, GLP-1 RAs may also exert direct disease-specific effects, particularly in neurodegenerative and substance use disorders, where central mechanisms appear to play a primary role. Clinical guidelines on obesity management, including the 2013 American Heart Association/American College of Cardiology and the 2016 American Association of Clinical Endocrinologists/American College of Endocrinology guidelines, highlight the importance of a structured lifestyle intervention program.8 These programs typically include a calorie-restricted diet, increased physical activity, and behavioral therapy, which together are recommended as the first-line treatment for individuals with overweight or obesity. Indeed many doctors require people to try diet and exercise alone before trying GLP-1s. These off-brand semaglutide and tirzepatide equivalents are mixed in a private compounding pharmacy and are not subjected to rigorous FDA testing. The high price of GLP-1s has created a market for less-expensive compounded versions of the drugs. Transform Your Life with Physician-Directed Care Thirteen of these studies used DXA to measure body composition, two used BIA alone, one used a combination of BIA and CT, and one used ADP. AFFM; bSame as “Study 1” in Blonde et al. (2016) ; cCalculated using mean weight loss in entire cohort. 1, 2 present the relative proportion of weight loss that could be attributed to FM and LBM/FFM with GLP-1RA and SGLT2i therapy, respectively. Cervical Health Month: When Women Should Get Screened However, in recent years, there has been a significant rise in the use of antiobesity medications such as GLP-1 RAs with promising results in weight loss and management 22,23. Given their effectiveness in controlling blood glucose and HbA1c levels, with additional weight loss benefits and minimal intrinsic risk of hypoglycemic episodes, GLP-1 RAs are now considered the first-line injectables for optimal glucose control in diabetic patients even before insulin treatment . In this narrative review, we have explored the varying effects of these agents on essential metabolic parameters such as blood glucose, cardiovascular health, weight management, blood pressure, and lipid profile in both diabetic and non-diabetic patients. Following this, the FDA-approved Wegovy® (semaglutide) was given as a treatment for weight loss in patients with a body mass index (BMI) of 27 kg/m2 or higher . Family physicians may feel angst when patients request these medications, considering that weight and body mass index (BMI) are flawed health metrics, and the current societal desire for thinness has murky origins. Existing GLP-1 receptor agonist therapies typically require subcutaneous administration which may be inconvenient for or not preferred by some patients, resulting in reduced adherence . In pharmacokinetic studies, it was found that the mean half-life was 116.7 h (5 days); hence, the most optimal and practiced form of dosing is weekly subcutaneous injections of the drug . Residues originate from GLP-1, GIP, and semaglutide, and some residues are distinct. These effects tend to be mild to moderate and are transient, mostly following dose increases.5,7 Patients should be counseled on adequate water intake. Most side effects are gastrointestinal and include nausea, vomiting, diarrhea, and constipation. If there are significant side effects a slower titration may be helpful but is usually limited by insurance. The cost can be prohibitive, most insurances require prior authorization and making patients aware of this up front helps reduce frustration and phone calls/messages. The treatment appeared to counteract the abnormal expression of 591 genes in the spinal cord that had been altered by nerve damage, especially those involved in inflammation, including TNF-α and toll-like receptors. In a study using rats with spinal nerve ligation, exenatide was found to reduce neuropathic pain, specifically by lowering sensitivity to touch (allodynia) 95-97. A separate double-blind study assessed exenatide's effect on intracranial pressure in women with idiopathic intracranial hypertension . This means that GLP-1 could help treat osteoporosis and similar bone issues, particularly in people with T2DM. In osteoporosis, GLP-1 RAs such as exendin-4 can help by increasing osteocalcin levels, a protein essential for bone health. Addressing the high cost and supply shortages of GLP-1 RAs is essential for improving patient access and optimizing treatment outcomes.Cardiovascular and renal outcomes are primarily derived from trials in participants with type 2 diabetes or established cardiovascular disease.These medications are expensive (price), and injections are more complex than oral medications (simplicity).Since these formulations are regulated differently from name brands, there is often inconsistency in how they are assembled, labeled, and dosed, making it challenging for doctors to understand exactly what their patients are taking and how it might affect them.A naturally occurring hormone in our body, glucagon-like peptide-1 (GLP-1) plays a role in regulating our blood sugar, appetite, and digestion.(1) Where data were reported for mean total BW and mean body fat percentage, we estimated mean FM as; BW divided by 100, multiplied by body fat percentage.Susan Jara is a health communications strategist and writer with more than 15 years of experience transforming complex medical information into clear, accurate, and engaging content for diverse audiences of patients and caregivers.Traditionally, obesity has been controlled with diet, exercise, behavior modification, and bariatric surgery. ROSE-010 provided dose-dependent pain relief in trials, especially with a 300-μg dose, showing benefits as soon as 20 minutes after administration. A GLP-1 analog, ROSE-010, was tested in IBS patients for pain relief, effectively increasing intestinal muscle movement . Research on constipation-predominant IBS patients showed lower GLP-1 receptor levels and serum GLP-1 compared to controls, which correlated with more abdominal pain . When Kessler reached his personal weight-loss target, he was developing some slight abdominal pains, so he decided to stop. "I'm not even sure everyone can trace back where the drugs are being made," he says. It's also common to lose some muscle mass along with fat while on these drugs, which can be problematic, Kessler writes. However, out of 43 groups in which it was possible to estimate the proportion of weight loss that could be attributed to LBM/FFM, in 27 groups this proportion of LBM lost ranged from 20% to 50%.New data also suggest that the use of GLP-1 RAs before metabolic or bariatric surgery may help high-risk patients with extreme obesity (BMI ≥ 70 kg/m2) lower the risk of post-operative complications.23 Previous studies have shown that weight loss before surgery can mitigate risk, however conventional lifestyle interventions or older anti-obesity medications have not led to sufficient weight loss to make a difference.24,25Some people take the drugs and lose weight with no side effects.This applies even if you haven’t lost weight through lifestyle changes alone.This prolonged digestion keeps us feeling full for longer, reducing the need to snack and helping control portion sizes, which naturally supports a calorie deficit needed for weight loss.In my experience, it is important for clinicians and care managers to have an upfront conversation with patients about what they might experience on a GLP-1 medication.Similarly, they should be aware of which symptoms are potentially harmful side effects of the medication. Originally developed to treat Type 2 diabetes, the drug also provides weight loss benefits, and more Americans than ever are using it for just that. “They’re smaller in molecular weight than peptide medications that mimic or interfere with endogenous bioregulatory peptides.” These side effects were observed in clinical trials for these products and make up the majority of the Yellow Card reports the MHRA receives for these products. Switching without medical advice may increase the risk of experiencing side effects or make the treatment less effective. The National Institute of Health and Care Excellence (NICE) also provides guidance for patients and the public on use of Tirzepatide (Mounjaro) for managing overweight and obesity. Using search engines such as PubMed, 3,730 articles were found to be on GLP-1 RAs alone in 10 years, with 1,194 articles on their role in weight management and control of obesity. With the present data available, it is well established that GLP-1 RAs are effective medications for lowering blood glucose levels and managing T2DM. Various clinical trials have reported these findings, which are discussed further in our study 11-14. #1 – Medvi: Best Overall GLP-1 Program for Safety, Transparency & Real Results If you cannot access or afford newer GLP-1 medications, a generation of older weight loss drugs is still available.High insulin levels can result in weight gain over time, so it’s important to eat foods and incorporate lifestyle habits that support both blood sugar control and insulin levels.The main concern with microdosing GLP-1 medications is that microdosing therapy may not be effective at helping you achieve significant weight loss and complete blood sugar control.But you can always tell them if you’d like to try a lower dose or manage your weight without the medication.GLP-1 receptor agonists also contribute to glycemic control via a reduction in body weight, which is beneficial for patients with type-2 diabetes .Some off-label prescribing even has accumulated a growing body of high-quality evidence.It acts as a primary site of glucose disposal (with lower skeletal muscle mass contributing to poorer glycaemic control ), and is a strong determinant of resting metabolic rate; and thus loss of skeletal muscle with weight loss may predispose individuals to a greater chance of weight regain . GLP-1 drugs are powerful medications that may not be appropriate for everybody. In the majority of people in clinical trials, these side effects have been mild or moderate. The weight loss reported in the above studies all occurred in volunteers who were also asked to maintain healthy eating and exercise habits. A more rapid decline in skeletal muscle and consequential increased risk of sarcopenia is concerning, particularly as individuals prescribed these therapies are usually already vulnerable to an increased risk of physical frailty (i.e., those with T2DM and/or obesity) . There were no clear differences between GLP-1RAs and SGLT2is in the magnitude of weight loss that could be attributed to LBM/FFM. Six groups saw a loss of LBM, FFM, or skeletal muscle but with a smaller relative contribution to total weight loss (0% to 19%), whilst another six reported an increase in LBM, FFM, or skeletal muscle mass. It is also common to see faster weight loss in the initial few weeks, followed by a few weeks of slower weight loss. Incorporating sources such as eggs, yogurt, lean meats, nuts, or legumes provides sustained energy, supporting weight management efforts naturally. Exercise also makes your body more sensitive to insulin, aiding in blood sugar control. Who should not take GLP-1 drugs? Konig et al. in their post hoc analysis summarized that dulaglutide caused a significant reduction of 16.7% in HBA1c and 25.4% in UACR, which, in turn, contributed to the benefits recorded for cardiovascular health 43,44. Similarly, the REWIND and HARMONY trials showed that dulaglutide and albiglutide also caused a noteworthy decrease in cardiovascular events. Numerous CVOTs have been conducted over the years, signifying significant benefits of GLP-1 RAs, with overall improved cardiovascular health and kidney function recorded . These findings have highlighted the emerging effectiveness of this class of medication. Additionally, patients significantly improved their daily walking ability compared to the control group 27,37. The MHRA has not assessed the safety and effectiveness of these medicines when used outside of their licensed use, for example when used for weight loss in people who are not obese or overweight. The recent advances in obesity medicine have led to many changes in the approach to patients with obesity and there is hope that this can be a manageable disease thus mitigating the consequences of it. Once a patient is on maintenance dose, follow-ups can be spread out, however, it may be beneficial to see patients more frequently if they continue to have weight loss or are not having the expected maintenance of weight. These weight-loss medications are intended for long-term use.What are the long-term effects of sustained GLP-1 RA use on cardiovascular, pancreatic, thyroid, hepatobiliary, and neurocognitive outcomes across diverse populations?Fiber offers numerous health benefits, and like fats, it slows digestion, helping you feel full longer.They estimated that people who stopped the drugs would return to their previous weight within about two years; those who took tirzepatide and semaglutide were projected to regain about 1.8 pound per month and to return to their baseline weight within about 1.5 years.FDA approves weight management drug for patients aged 12 and older.Glucagon-like peptide 1 (GLP-1) agonists belong to a class of type-2 diabetes medications that mimic the function of the GLP-1 hormone secreted by the pancreas . Evidence from dual-energy X-ray absorptiometry and MRI sub-studies suggests that 25–45% of total weight loss with semaglutide and tirzepatide may come from reductions in lean body mass.90 Although this proportion is similar to that seen with lifestyle interventions,91 the decline in lean mass may have implications for mobility, metabolic rate, and physical function, particularly in older adults or those with sarcopenic obesity. However, these strategies are often insufficient to achieve and sustain weight loss.9,10 Many patients struggle to maintain the necessary behavioral changes long term, leading to modest results which are often inadequate in addressing the complex physiological, genetic, and environmental factors underlying obesity.11 On average, patients regain one-third of the weight lost (5–10% of baseline bodyweight) within the first year of treatment discontinuation, and nearly half of patients return to their initial weight within five years.9 Consequently, lifestyle interventions frequently require supplementation with pharmacological treatments to achieve more substantial weight loss outcomes. Long-term safety concerns, particularly regarding potential risks to the thyroid and gallbladder, are still being explored.2,3 Additionally, weight regain after treatment discontinuation and reductions in lean mass have raised new clinical concerns, while issues surrounding cost and accessibility present barriers to the widespread adoption of these drugs.4, 5, 6, 7 This review explores the evolving role of GLP-1 RAs, highlighting their benefits beyond weight loss, key safety and policy considerations, and future directions for optimizing their use. The only study administering semaglutide reported 5.0 kg weight loss after 12 weeks of treatment in individuals with obesity . DXA remains a prominent and preferred technique in clinical trials, balancing a high level of accuracy with comparatively lower costs than MRI and CT. The aim of this narrative review is to describe the effects of GLP-1RAs and SGLT2is upon body composition, with a particular focus on LBM and skeletal muscle. It acts as a primary site of glucose disposal (with lower skeletal muscle mass contributing to poorer glycaemic control ), and is a strong determinant of resting metabolic rate; and thus loss of skeletal muscle with weight loss may predispose individuals to a greater chance of weight regain . Importantly, the glucose-dependent mechanisms of action of both therapies mean that their beneficial effects come with low risk of hypoglycaemia, particularly when not used with sulphonylureas or insulin . Given the sociopolitical origins of our weight-focused culture, how should we address our patients' desires to achieve a certain weight, even if there is no strict medical need to do so? The cultural fear of weight gain and larger body size has insidious origins. The Mayo Clinic Diet helps you achieve lasting weight loss with custom meal plans and proven strategies. Some of the most common side effects are gastrointestinal effects such as nausea, vomiting, and diarrhoea. Before switching from one GLP-1 medicine to another, including between brands containing the same type of GLP-1, you should consult a healthcare professional for advice. For further information about use of online pharmacies, please also refer to the General Pharmaceutical Council’s guide on how to keep safe when getting medicines or treatment online. In conjunction with all the effects, GLP-1 RAs have been found to lower weight and aid in weight management. We can promote healthy behaviors and acknowledge the dissonance of living in a diet-entrenched society with the understanding that weight loss may not be the answer. Even without a medical need for weight loss, we can work with patients toward an informed approach that respects their bodily autonomy and recognizes their societal discord and experiences living in larger bodies. Because patients often seek validation from physicians to lose weight, we can acknowledge their goal while emphasizing a more holistic approach to health, encouraging patients to engage in exercise they enjoy and eat nourishing foods that make them feel good and not deprived. GLP-1 agonists' effectiveness may be limited since most people regain weight when they stop taking the medication (effectiveness). Although more research is needed to fully understand the long-term effects and potential risks, the data so far are promising. GLP-1 receptor agonists such as Wegovy®, Ozempic®, and Mounjaro™ represent significant advancements in the treatment of obesity. While Mounjaro™ is not FDA-approved for weight loss, it has been widely prescribed off-label due to its effectiveness in promoting weight reduction, similar to Ozempic®. It’s also approved to treat moderate-to-severe obstructive sleep apnea (OSA) in people with a larger body size. Zepbound is the FDA-approved version of tirzepatide for weight loss. After 40 weeks, people receiving Mounjaro saw a better reduction in hemoglobin A1C levels (average blood sugar over 3 months) compared to Ozempic. And it may not result in the same amount of weight loss, either. And it can also cause weight loss as a side effect. Figure 1. The effects of GLP-1 agonists on targeted tissues. Participants who received Wegovy®, in combination with lifestyle interventions, achieved an average of 15-18% reduction in body weight. Wegovy®, with the active ingredient Semaglutide, is a GLP-1 receptor agonist approved by the Food and Drug Administration (FDA) in June 2021 for chronic weight management. One therapeutic class that has made considerable advancements in the management of weight and glycemic control is glucagon-like peptide-1 (GLP-1) receptor agonists. Collectively, the available evidence suggests that the initiation of GLP-1RA or SGLT2i therapy results in weight loss that is primarily derived of FM. Whether the same results are observed when exercise is combined with weight loss elicited by GLP-1RAs and SGLT2i therapy is currently unknown, and requires testing in robust experimental research. Victoza (liraglutide) is a once-daily injection for Type 2 diabetes in adults and children ages 10 and older. One study found that adults taking the highest Trulicity dose (4.5 mg) were able to lose up to 10 lbs over 9 months. Trulicity (dulaglutide) is a once-weekly injection for Type 2 diabetes in adults and children ages 10 and older. The activity of GLP-1 deteriorates with poor glucose control in the body; hence, its efficacy is reduced further in patients with diabetes . Glucagon-like peptide 1 (GLP-1) agonists belong to a class of type-2 diabetes medications that mimic the function of the GLP-1 hormone secreted by the pancreas . Thus, current studies are interested in the differential efficacy, benefits, and side effects of these different forms of semaglutide. There is a substantial and growing body of research comparing the efficacy of different clinical trials and examining long-term safety. It's the faster pace of weight loss that occurs with GLP-1 drugs that can make facial changes more obvious. In fact, BMI only accounts for ∼17% of the risk of insulin resistance and subsequent type 2 diabetes in BMI ≥ 25 kg/m2 population . The potential disease impact of obesity has been widely debated and explored in recent research. Overall, these studies indicate that danuglipron is a promising antidiabetic drug that may increase adherence in patients given its form of delivery and ease of administration. Most significantly, this study found that danuglipron was able to reduce HbA1c% (ranging from 0.9% to 1.2% points lower depending on dosage) and weight (2.2 kg to 7.2 kg reduced depending on dosage) after just 28 days of administration . When administered at a dose of 300 mg, twice a day, patients reported side effects such as nausea and vomiting. Earlier this year, the FDA approved a label update to permit Rybelsus® first-line utilization for adult patients with type 2 diabetes. Danuglipron is currently not FDA-approved as it has not passed phase three of clinical trials. Tirzepatide, under the name Mounjaro®, was approved by the FDA on May 14, 2022, for the treatment of type 2 diabetes . It is likely that fewer have discussed Rybelsus® relative to Ozempic®, given the lower average effectiveness in terms of weight loss. By activating GLP-1 peptides, these medications affect body weight in many ways, including inhibiting glucagon and stimulating insulin release, and resulting in an average loss of 5% to 15% of body weight sustainable for at least 12 months.1–3 Following a healthy lifestyle program such as the Mayo Clinic Diet is a great way to support your weight-loss journey when taking GLP-1 medications. Popular brands of the GLP-1 receptor agonist semaglutide — including Ozempic and Rybelsus —are approved by the Food and Drug Administration (FDA) for treating diabetes, while Wegovy is FDA-approved for obesity management. The difference between these particular medications is dosage and the formulation. These are effective, game-changing medications, but they need to be used appropriately.” – Jaime Almandoz Despite the abundance of attention to the cost of GLP-1s and some patients’ challenges in obtaining the drugs, panelists emphasized that access to drugs does not equal access to care. "They have changed the landscape of weight loss," says Kessler. He also breaks down the science behind obesity, and what makes these drugs so effective. Dr. David A. Kessler has always been in the business of keeping people healthy – but by his own admission, he hasn't always applied that to himself. In fact, lean body mass can account for up to 15-40% of total weight loss from GLP-1 therapies. However, studies have shown that a reduction in muscle mass accompanies total weight loss. “We are championing research to ensure people living with obesity can have access effective treatments to reduce adiposity while maintaining muscle mass critical to their well-being, and supporting durable long-term outcomes.” Research indicates potential for new wave of breakthroughs in maintaining lean mass for patients taking GLP-1-based medications The field of weight management is evolving–and fast. Others have called to question the utilization of these drugs off-label for individuals that are not in the categories of a BMI above 30 or above a BMI of 27 with another weight-related condition threatening their health. This may be attributed to the relatively recent approval of several of these medications in adults and current ongoing trials such as STEP YOUNG for Wegovy® and SCALE KIDS for Saxenda® . There is also growing evidence for off-label antiobesity medications such as metformin and topiramate . GLP-1 agonists are typically approved for the management of conditions such as type 2 diabetes and in some cases weight management but are growing in popularity for their off-label utilization. In some cases, metabolic/bariatric surgery may be considered an appropriate treatment for long-term weight loss. From week 20 to week 68, participants who discontinued the drug regained an average of 6.9% of their baseline body weight, while those who continued treatment lost an additional 7.9%.6 These findings suggest ongoing treatment with GLP-1 RAs is required to maintain improvements in weight and health, highlighting the chronicity of obesity.This is why it is important that providers and care managers help patients understand that obesity and overweight are chronic diseases and not something simply caused or addressed by choices and changes.This increase prompts the pancreas to release insulin to lower blood sugar to safe levels.Though less common, serious side effects can occur and should be discussed with your provider before starting treatment.Semaglutide which is given subcutaneously was first approved by the FDA in 2017 for the use of type 2 diabetes management under the brand name of Ozempic® .After some time on the drug, it will be assisting them to maintain a weight, rather than continue to lose, but that doesn’t mean the drug’s not working anymore.There is a growing need for further research to evaluate the metabolic effects of GLP-1 microdosing in humans, as current data on its impact is limited.Wegovy, the high-dose Ozempic used for weight loss, costs up to $1,350 a month, which, again, may have to be paid in perpetuity since any lost weight can pile back on if you stop taking it. Additionally, the higher risk of surgical and long-term complications necessitates careful patient selection.20,21 As such, bariatric surgery is typically reserved for individuals with severe obesity (body mass index BMI ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 with obesity-related comorbidities) who have not achieved sufficient weight loss with other interventions.22 In contrast, GLP-1 RAs are generally recommended for those with a BMI ≥ 30 kg/m2 or a BMI ≥ 27 kg/m2 with obesity-related comorbidities. Lifestyle interventions, alternative anti-obesity medications, and bariatric surgery offer different approaches for weight loss and may provide useful context for evaluating the overall impact of GLP-1 RAs. While GLP-1 RAs have demonstrated substantial efficacy in promoting weight loss, it is useful to first examine other treatment modalities in obesity management. However, it showed significant weight loss potential in clinical trials, leading to its approval for weight management. If you are using a GLP-1 medicine and think you might be pregnant, speak to a healthcare professional straight away. In some animal studies, GLP-1 medicines were found to be harmful to the unborn foetus, although more information is needed to see whether or not this same effect would be seen in humans. A full list of the known side effects can be found in the product information for the individual medicines. Most side effects are mild to moderate in severity or short in duration. This opens the door to making mistakes—ones that could worsen your side effects, affect how much weight you’ll lose, or even cause new health issues. That’s why the UpToDate® clinical decision support suite recently enhanced its content related to GLP-1s, diabetes, and obesity to support clinical decision-making and patient counseling. They also need resources to help answer their questions about titrating doses and transitioning patients onto therapies, monitoring for side effects, and ensuring patients are informed about potentially harmful fraudulent drugs. We searched for published studies reporting data on the effects of GLP-1RAs and SGLT2is on body composition using the online database, PubMed, from inception to August 2019, using search terms related to GLP-1RAs, SGLT2is, weight loss and body composition. Both classes of therapy also elicit clinically relevant weight loss , with liraglutide gaining an independent license (at a higher dose of 3 mg) for use in obesity management. GLP-1 weight loss treatments are transforming how we approach obesity and weight management. Each utilised BIA to assess body composition, but only one study reported changes in both total BW and FFM. Two assessed changes over 12 weeks, reporting 3.3 and 2.9 kg weight loss, of which 30% and 52%, respectively, could be attributed to LBM 62,63. Using the weight loss observed in the entire population after 104 weeks (2.8 kg), it was estimated that approximately one-third (32.1%) of weight loss elicited in this trial comprised of FFM. It’s possible to still lose more weight through more traditional diet and lifestyle interventions. Along with understanding the process to titrate up to full dosage, patients need to be informed how to manage missed doses. Walking through how to use the device with the patient is extremely valuable, particularly because the medication is so expensive. Similarly, they should be aware of which symptoms are potentially harmful side effects of the medication. It may also be helpful for them to understand that during the first few months, many patients are consistently losing weight, some quite rapidly. In my experience, it is important for clinicians and care managers to have an upfront conversation with patients about what they might experience on a GLP-1 medication. I would highly encourage professionals to access an evidence-based and current clinical decision support solution just as a handy resource to familiarize themselves with recommendations regarding GLP-1 weight-loss indications and therapeutic uses. Today, many of the GLP-1s are approved to treat weight loss, and it has practically become their primary indication. Panelists also challenged listeners to think beyond simple dollars and cents and consider the holistic value these drugs provide to patients—including dramatic improvements in quality of life, fewer doctors’ visits and medications, and the ability to do activities they couldn’t do before. One recent paper found nearly 39,000 cardiovascular events were avoided when patients had access to obesity treatment, along with improvements in chronic kidney and liver diseases. These drugs can also produce side effects that may spur changes in eating habits, which can lead to safety risks or worse health outcomes if not appropriately managed. GLP-1 receptor agonists (GLP-1s)—better known by brand names Ozempic, Wegovy, Mounjaro, or Zepbound— are often referred to as “miracle drugs.” GLP-1s were originally developed to help regulate blood sugar in people with type 2 diabetes. However, Novo Nordisk, Ozempic’s manufacturer, released results from two clinical trials in November 2025 that showed that taking an oral GLP-1 didn’t slow disease progression among people with Alzheimer’s compared to those who took a placebo. However, a study conducted by Diamant et al. found that the use of exenatide once weekly has nonsignificant effects on LDL-C levels with a change of -0.05 mmol/L ± 0.05 mmol/L, suggesting that the effect of GLP-1 RAs on LDL-C levels requires further research .“If you’re constantly not feeling well, maybe you’re on a dose that’s too high or you’re not on the right medication.Foods that contain healthy fats, like olive oil and avocado, are still important to eat in moderation for the health benefits, but try to skip fried items, which tend to be harder for the GI tract to handle and offer little nutritional benefit.By increasing GLP-1 levels, you can better support weight loss and diabetes management.Nonsignificant changes in HDL-C levels (-0.04 to 0.00 mmol/L) were reported following liraglutide treatment . People who are trying to lose weight will go to great lengths, and maybe rightfully so, to find the drug that is doing well for them. If a person is doing really well on semaglutide, let’s say, and all of a sudden it becomes unavailable, there may be a temptation to go try to get it at such a place. Providers need to use every opportunity to make sure patients understand and are comfortable with this concept. Although not formally FDA-approved for weight management, it is commonly used off-label for this purpose due to its demonstrated effects on weight loss. This surpasses the weight loss achieved with most currently available weight loss medications. Of the 27 studies identified reporting changes in body composition with SGLT2i therapy, 13 reported changes in TBW, 12 of which reported losses; ranging from 0.2 to 2.4 kg (7% to 100% of total weight loss). In clinical trials, about 6 percent of Wegovy and Zepbound users dropped out due to side effects, mostly gastrointestinal issues such as vomiting and nausea. The results of major clinical trials suggest how much weight the average user may expect to lose. They can be a powerful part of a plan to achieve and maintain a healthy weight, he says, but the drugmakers and the FDA should do more to educate consumers about the side effects. GLP-1s, while highly effective, are therefore only one piece of a multidisciplinary health care puzzle. Whether the drugs can be used to prevent or treat dementia is also being studied, with mixed results. We’ve also seen data that semaglutide has been shown to have anti-inflammatory and cardiovascular benefits, which can further protect the kidneys from damage.” Studies suggest that GLP-1 receptor agonists may improve cardiovascular outcomes, reduce inflammation and enhance metabolic health. “This isn’t a failing of the medicines—it reflects the nature of obesity as a chronic, relapsing condition. As a pharmacist specializing in endocrinology and diabetes management, like most in the field, I have been familiar with this drug class for many years. It is difficult to turn on the TV, open your phone, or engage in any kind of media today and not hear something about Glucagon-like peptide-1 receptor agonist medications (these will be referred to as “GLP-1 medications” or “GLP-1s” from here on). Tirzepatide also targets GIP receptors, potentially leading to greater average weight loss. Studies have shown contradictions regarding the effect of GLP-1 RAs on LDL-C levels in the body, specifically with liraglutide or exenatide. These findings suggest that GLP-1 RAs may positively modulate cholesterol metabolism and dyslipidemia beyond their antidiabetic effects. Similar evidence from another study in 2018 showed that GLP-1 RAs modulate metabolism similar to statins by suppressing HMG-CoA reductase and SREBP-1C (sterol regulatory element-binding protein 1C) . Understanding these mechanisms could help manage dyslipidemia and cardiovascular risk . To lose weight, especially harmful belly fat, combine diet and exercise Pricing for the semaglutide pill is lower than that of the injectable version for those paying cash. "It only makes sense that the weight of their passengers also impacts their costs," Kahyaoglu told The New York Times. “GLP-1 medications have transformed the treatment of diabetes and obesity, but they can also increase the risk of muscle loss,” said Rebecca Gottlieb, Ph.D, Vice President of Advanced Sensor Technologies at Biolinq and lead author of the study. GLP-1 receptor agonists (GLP-1s) are a class of medications originally developed for type 2 diabetes but have gained widespread use for weight loss due to their effects on appetite and metabolism. Oral semaglutide has demonstrated efficacy in both diabetes and obesity management.96,97 Cardiovascular safety was first established in the PIONEER 6 trial,98 with the more recent SOUL trial demonstrating a significant reduction in MACE compared to placebo among individuals with type 2 diabetes and high cardiovascular or renal risk.99 These findings support the potential of oral semaglutide for broader clinical use. In the case of the GLP-1 drugs, the weight loss caused by the initial drop in appetite is undercut by an apparent exponential increase in caloric intake as our body ratchets up our hunger again. NICE has recommended semaglutide as an option for weight management - weight loss and weight maintenance. Randomized controlled trials (RCTs) of each of these 3 drugs showed they were the top producers of body weight reduction compared with placebo, according to findings published online today in Annals of Internal Medicine.1 Fountain integrates weight management with broader telehealth services (hormone therapy, peptides, wellness labs). And thanks to telehealth, patients can now access these treatments safely online without visiting a doctor’s office. Once-weekly semaglutide in adults with overweight or obesity. Addressing these questions will be critical to optimizing the clinical and public health impact of GLP-1 RAs. Continued efforts to improve real-world implementation will be essential to ensuring that GLP-1 RAs deliver meaningful clinical and public health benefits across a range of chronic conditions. Dual agonists such as tirzepatide (GLP-1/GIP) have demonstrated superior weight loss and glycemic control compared to GLP-1 RAs alone,104 likely due to complementary mechanisms involving both incretin pathways. Comprehensive long-term studies will help clarify the risk-benefit ratio of prolonged GLP-1 RA therapy. Indeed, the prescription weight-loss drug market grew 72% more than initially forecasted in 2023, ballooning to a 2.3 billion dollar industry . Ozempic® has skyrocketed demand in the pharmaceutical space for the weight-loss drug market. Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) such as semaglutide (Ozempic®) have recently risen exponentially in popularity, in part due to their prevalence on social media platforms, and celebrity endorsements. This review emphasizes the importance of informed decision-making, as well as the need for further research to guide future clinical practice. Subsequently, the popularity of the pharmaceutical weight-loss drug market has grown over the past few years to meet growing demand. Recent insights into body composition changes, potential psychiatric effects, and perioperative risks highlight the importance of individualized care and ongoing monitoring. These agents now play a central role not only in weight management and diabetes care but are also being investigated in a growing number of conditions, including cardiovascular, renal, hepatic, neurologic, and substance use disorders. Longitudinal studies should investigate how these agents impact long-term health outcomes, such as the incidence of cardiovascular diseases and mortality. While current studies have demonstrated substantial short-term weight loss and metabolic improvements, the sustainability of these outcomes over extended periods requires further exploration. Previous shortages of GLP-1 RAs impacted patient care, leading to concerns that these medications should be reserved for patients with diabetes rather than weight loss in otherwise healthy individuals.94 These concerns highlight the importance of stable supply chains and strategies to mitigate shortages, including increasing production and ensuring fair distribution.95 Public awareness campaigns are also essential to educate individuals about the benefits and potential risks of GLP-1 RAs, fostering informed decision-making and broader acceptance of these treatments. In the STEP-9 trial, use of semaglutide led to greater weight loss and improvements in knee pain and physical function compared to placebo in patients with obesity and moderate-to-severe osteoarthritis-related symptoms.45 However, the extent to which these benefits reflect weight loss vs. direct anti-inflammatory or structural effects remains unclear, as the trial did not assess imaging or biochemical markers of joint degeneration.45 Preclinical studies suggest that GLP-1 RAs may exert anti-inflammatory and cartilage-protective effects within the joint,46 but further research is needed to determine whether these translate into structural improvements beyond symptomatic relief. New data also suggest that the use of GLP-1 RAs before metabolic or bariatric surgery may help high-risk patients with extreme obesity (BMI ≥ 70 kg/m2) lower the risk of post-operative complications.23 Previous studies have shown that weight loss before surgery can mitigate risk, however conventional lifestyle interventions or older anti-obesity medications have not led to sufficient weight loss to make a difference.24,25 Beyond GLP-1 RAs, current FDA-approved pharmacotherapies for chronic weight management include orlistat (a lipase inhibitor that reduces fat absorption), phentermine-topiramate (a sympathomimetic appetite suppressant combined with a gamma-aminobutyric acid receptor modulator), naltrexone-bupropion (an opioid antagonist combined with a dopamine/norepinephrine reuptake inhibitor), and setmelanotide (a melanocortin-4 receptor agonist).12 Besides setmelanotide, which is indicated for patients with rare genetic forms of obesity, these alternative anti-obesity medications result in modest weight loss, typically ranging from 3 to 9% of baseline body weight.12 These benefits are smaller than the 15–20% weight loss observed with GLP-1 RAs or co-agonists.1