The individual risk of ischemia or heart failure consequences should guide the treatment choice because sodium/glucose cotransporter-2 (SGLT-2) inhibitor therapy also lowers CV events (with impact predominantly driven by a reduction in heart failure complications). GLP-1 RAs are currently used in treating patients with T2D and consistently result in weight loss, in addition to lowering blood glucose levels. Three long-acting drugs in the market represent this approach which are liraglutide, semaglutide, and tirzepatide. Maladaptive reactions that occur after weight loss are also significant components of the pathophysiology of obesity. Overall, these findings demonstrate the efficacy of semaglutide in promoting weight loss and improving cardiometabolic risk factors, which may have implications for the management of obesity and related disorders. In the semaglutide treatment groups, the mean decrease in body weight from baseline to week 68 was significantly higher compared to the placebo group. In obese or overweight patients without diabetes, semaglutide has demonstrated considerable weight loss with acceptable safety . The average follow-up time was 3.8 years, and the liraglutide group had fewer patients die from cardiovascular reasons overall. In 2017, LEADER investigators reported that liraglutide therapy resulted in significantly lower nephropathy events than placebo, although there was no significant difference in retinopathy events. The LEADER trial published in 2016 assessed the impact of liraglutide on cardiovascular outcomes in 9340 participants with advanced T2DM and high baseline cardiovascular risk. The combined strategy also led to a greater decrease in body fat percentage by 3.9 percentage points, which was roughly twice that observed in the exercise group (−1.7 percentage points) and the liraglutide group (−1.9 percentage points). The trial was conducted at 43 sites in the United States, and patients received either ExQW 2 mg for 24 weeks or ExBID 5 μg for 4 weeks, followed by ExBID 10 μg for 20 weeks. After 26 weeks, the HbA1c (%) reductions with EQW were −1.53, −1.63, and −1.15, as compared to MET, IOP, and SITA, respectively. Of the 415 patients who completed the 26-week course, 390 (194 EQW patients and 196 IG patients) enrolled in the extension trial. Efficacy analyses included changes from baseline in glycated hemoglobin (HbA1C) and cardiovascular risk factors. The rapid weight loss can be visualized in many areas of the body and one of these manifestations known as “Ozempic face” occurs when fat pads in the face are rapidly depleted 177,178. It is thus not surprising that these same side effects of rapid weight loss are seen as a class effect. As the newer agents in the GLP class have become incredibly potent where users are losing an estimated 15-20% of body weight, with much of the weight loss occurring in the initial weeks of initiating the drug 175,176. Furthermore, patients with type 2 diabetes are inherently at higher risk of pancreatitis . Early studies on patients with type 2 diabetes treated with incretin therapy including GLP-1s and dipeptidyl peptidase-4 (DPP4) inhibitors did demonstrate an association between drug usage and the development of pancreatitis . These varied treatment responses likely originate from our limited understanding of the mechanisms of weight regulation. Obesity may present itself with multiple clinical phenotypes and also varied treatment responses. Obesity as defined by The Obesity Society (TOS) is a multi-factorial chronic disease that results from excess fat accumulation that presents a risk to health . Achieving success with pharmacologic treatment and then weaning to avoid future negative effects would be ideal. A significant disadvantage of using these medications is the high rate of weight regain when they are discontinued. Wholesale acquisition costs differ between brand nameGLP-1 drugs.The study found that liraglutide 3.0 mg may provide health benefits for people with prediabetes and obesity.As a result, recommendations prioritize GLP-1 RA treatment for individuals with atherosclerotic vascular disease (such as previous CV events) .We can also redirect the conversation toward health-promoting behaviors.Clinical trial outcomes will determine whether these will be useful either on their own or in conjunction with GLP-1 agonists.Of these 69 patients, 40 patients were transitioned to generic second‐generation AOMs after the MWLB ended (Table 3).FIM interventions can help overcome many common barriers to healthful eating, including cost, time, access, and knowledge. Those who completed the entire two-year treatment period lost 7.8 kg from the time the weight loss began at run-in. After two years, participants randomized to liraglutide 2.4 or 3.0 mg (pool group) sustained a mean weight loss of 5.3 kg. Serious adverse events, such as pancreatitis, cancer, and psychiatric effects related to all doses of liraglutide, especially the 3.0 dose, were a concern, and some individuals withdrew from the study. Cardiovascular risk reduction was the greatest benefit reported after liraglutide administration. These medications work by imitating a natural hormone that slows digestion and helps individuals feel full for longer. These findings support the integration of GLP-1 RAs into comprehensive, individualized obesity management strategies. Lastly, emerging insights into biomarkers such as leptin and satiety hormone responses should prompt trials investigating personalized or stratified approaches to GLP-1 RA therapy to maximize efficacy and minimize discontinuation . Furthermore, underrepresented populations - including adolescents, the elderly, and individuals with psychiatric or eating disorders - require focused study. Reliance on post hoc analyses in certain studies also limits the strength of causal inferences. Studies suggest that GLP-1 drugs are not a direct cause of depressive symptoms in weight loss . Newer strategies for weight maintenance have focused on preserving or even increasing lean body mass to counteract the decreases in energy expenditure thereby allowing for sustained weight loss 105,263. Other studies have found little to no impact of physical activity on maintaining weight loss . Most effective weight loss from a dietary standpoint is seen over 3 to 6 months, with at least one-third of patients regaining lost weight within the first year and the majority of patients regaining the weight after five years 224,225. Additionally, while some data extend to 120 weeks, real-world evidence on treatment adherence, long-term safety, and durability beyond two years is still lacking. Beyond these effects, they modulate central appetite-regulating pathways, particularly in the hypothalamus and brainstem, reducing reward-driven eating behaviors. Notably, adolescents receiving exenatide showed improved weight maintenance, with lower leptin responses predicting better outcomes . With semaglutide and tirzepatide gaining the most media attention and curiosity in recent years due to their high effectiveness, we’ll focus on these two medications. Since then, several others have followed, including dulaglutide (Trulicity), liraglutide (Victoza, Saxenda), semaglutide (Ozempic, Wegovy), and the latest FDA-approved medication, tirzepatide (Mounjaro, Zepbound). LEXINGTON, Ky. (Aug. 18, 2025) – You’ve likely heard about glucagon-like peptide-1 agonists — commonly referred to as GLP-1 medications, and more widely recognized through pharmaceutical brand names like Ozempic and Mounjaro. Costs remain a major barrier, particularly for semaglutide and tirzepatide, while liraglutide has become more affordable since its patent expired. Most of the studies included in the reviews were funded by the companies that manufacture the drugs and were shaped by those companies in terms of design, analysis, and reporting. The reviews found little to no difference between the drugs and placebo when looking at major cardiovascular events, mortality, or quality of life. This review synthesizes findings from studies assessing agents such as semaglutide, liraglutide, tirzepatide, and exenatide in diverse populations, including adults with and without type 2 diabetes and adolescents with severe obesity. In the life insurance space, companies that cover mortality risk will benefit the most from GLP-1s to the extent that the treatment of diabetes, obesity and related co-morbidities translates to longer life spans for the insured population. Not all of these experimental drugs will necessarily make it to market, but one of the primary roles they may play if they do is as “long-term maintenance dosing” for people who’ve lost a sufficient amount of weight on injectable medications, Dushay said. Lilly, which also makes Zepbound and Mounjaro, reported last year that a midstage trial found that people taking orforglipron for 36 weeks lost an average of 15% of their body weight – about the same amount as oral semaglutide in less time. However such risk in humans is still under investigation. GPL-1 therapies are efficacious for reducing weight. The guideline does not cover the use of GLP-1 therapies in pregnant women as these medications have not been tested in this population. The lack of overlap between the two stripes indicates a significant difference in efficacy between the two drugs. Points connected by a line originate from the same study arm, while points sharing the same color belong to the same study. Owing to the limited number of time points available for some drugs, it was not possible to estimate the k values individually for each drug. The Emax values for 12 GLP-1RA drugs ranged from 4.25 kg to 22.6 kg, with Retatrutide exhibiting the highest Emax value and Liraglutide the lowest. The detailed demographic and clinical characteristics of the participants are provided in Supplementary Tables S3 and S4. Programs do not include the cost of GLP-1 medications. Join a judgment-free community of people who are also on a GLP-1 through WW’s social platform, Connect. Log your weight and activity to get a clearer picture of your journey. Not a randomized, controlled clinical trial. This review examines their expanding role, evaluating efficacy compared to alternative treatments, emerging indications, ongoing challenges, and future directions. Nonetheless, while these agents are well-tolerated, they have some side effects, most importantly gastrointestinal, which warrant attention. GLP-1 RAs provide a multifactorial and practical approach to managing T2DM and related metabolic conditions, along with obesity, dyslipidemia, and hypertension. GLP-1 RAs’ distinct and unique mechanism of enhancing insulin release in response to glucose, increasing satiety, and slowing gastric emptying can be attributed to the previously mentioned benefits of weight management and glycemic control. ROSE-010 provided dose-dependent pain relief in trials, especially with a 300-μg dose, showing benefits as soon as 20 minutes after administration. Legends Keto Many Diet Pills Have Serious Side Effects Despite doing all the right things, the weight never budged. If I did lose weight, it was through such extreme measures that it wasn’t sustainable, and I would gain it right back. Already on blood pressure medication, I knew it was only a matter of time until a diabetes diagnosis would follow if something didn’t change. In June 2022, my father, who had struggled with obesity his entire life, passed away unexpectedly from a Type 2 Diabetes-related cause. 1. Weight Loss Evidence from Clinical Trials in Diabetics and Non-Diabetics The growing popularity of GLP-1s could transform how obesity is viewed and managed. The U.S. obesity market is forecast to reach $44 bn in 2030 — up from just $0.5 bn in 2020. This could lead to a paradigm shift in health care and also impact other sectors, from biotech to food. Although ample clinical trials and meta-analyses have been conducted to highlight these limits separately, more work is needed to narrate all these metabolic parameters under one umbrella. These compounds have similar amino acid sequences compared to endogenous GLP-1, with small alterations, a free fatty acid side chain that binds to albumin, explicitly seen in liraglutide and semaglutide, that alter their pharmacokinetic properties (e.g., increased half-life and duration of action) . In conjunction with all the effects, GLP-1 RAs have been found to lower weight and aid in weight management. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been developed to manage type 2 diabetes mellitus. This study developed pharmacodynamic models for 12 GLP-1RA drugs and conducted quantitative analyses of their time-course relationships, dose-response relationships, factors influencing efficacy, dropout rates, and adverse events. While remission can occur in rare cases, the disease mechanisms underlying obesity often persist.(27) Framing GLP-1 medications as acute treatment risks undervaluing their potential for long-term medical management of a serious metabolic disease. GLP-1 receptor agonists alone do not represent cures for obesity.(24) The weight lowering effects appear to persist only as long as the medication is taken consistently and at the full therapeutic dose. For uninsured patients or those with high-deductible plans, out-of-pocket costs likely still approach the full list price.(17) Medicare enrollees also pay more since current federal law prohibits Medicare from covering medications for weight loss. As with any medication, GLP-1 drugs have potential risks and adverse effects that must be considered before initiating treatment. It’s a hurdle many people face during a weight loss journey, Rickel says. I was leery of weight loss ‘wonder drugs,’” she says. Glucagon-like peptide-1 receptor agonists (GLP-1s or GLP-1RAs) are used in the management of obesity and type 2 diabetes. Studies are also needed to determine whether differences exist in nutritional status, weight reduction, health, and quality of life when GLP-1 or GIP/GLP-1 RAs are used concurrently with Medical Nutrition Therapy guided by an RDN. The most transformative potential impact of GLP-1 receptor agonist medications is how they could reshape industries, markets, and social norms if adoption became extremely widespread.Log your weight and activity to get a clearer picture of your journey.By incorporating Bio Detox Lean Keto ACV Gummies into your daily routine, you may experience improved digestion, increased energy levels, and successful weight loss.In a different diabetic neuropathy model, the combination of oral amitriptyline and subcutaneous liraglutide and a formulation combining both drugs showed significant improvements in pain and inflammation markers in the sciatic nerve .Even so, there is still limited or uncertain evidence about their long-term safety, possible side effects, and how financial ties might influence study results.By helping to regulate blood sugar, these medications support the management of Type 2 diabetes.Supplementation can help meet protein and micronutrient needs for patients who are unable to consume adequate nutrition through usual dietary intake.As a result, they may not eat enough protein, miss key nutrients, or lose weight too quickly. Get CNN Health's weekly newsletter Obesity has harmful effects on various body systems, most notably on the cardiovascular and endocrine systems, but also on the kidneys, liver, lungs, joints, and immune system . Severe obesity, which is defined as a BMI over 40 kg/m2, is an alarming public health issue . Obesity is traditionally defined as an excess of body fat, and is classically categorized in clinical practice in terms of body mass index (BMI). This is because GLP-1 medicines may reduce the effectiveness of oral contraceptives in those who are overweight or obese. 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. Eventide was an injection-free GLP-1 agonist that showed promise, but ultimately didn’t get FDA approval for its application to treat type 2 diabetes. “No form of dulaglutide is approved for weight management,” says Kushner, who adds that it’s rarely, if ever, prescribed for off-label use. Dulaglutide is the GLP-1 agonist sold under the brand name Trulicity, and it’s solely available for controlling type 2 diabetes. The new generation of weight loss drugs: The pros and cons of GLP-1s Precision medicine itself is an area of medical management that tries to match personalized treatments or food content, to individual genetics, microbiome, metabolism, age, and sex. However, consumption of ultraprocessed food has been shown to induce an even greater consumption of calories, and therefore leads to weight gain. This can be attributed to the metabolic adaptations that are seen to occur in those with obesity. As expected, there was weight regain, but there still was an overall 5.6% net loss of weight by the end of 120 weeks . Taming Tumor Chaos: Researchers Uncover Key to Improving Glioblastoma Treatment Weight loss maintenance outcomes of successful medical weight loss bundle patients (defined as BMI 2 at 12 mo) In total, 105 patients enrolled in the MWLB achieved an average weight loss of 22.2% ± 3.3% at 12 months compared to baseline (Table 4). On average, most patients required more than one generic AOM to help maintain weight loss after discontinuing GLP‐1 RA therapy, which is why utilization was greater than 100%. Of the 69 patients, 80% were given metformin extended release, 20% were given phentermine, 32.5% were given topiramate, 32.5% were given bupropion, and 2.5% were given naltrexone to help maintain weight loss. Of these 105 patients, 7 did not desire treatment with GLP‐1 RAs due to adverse effects or other reasons, and 4 individuals left the MWLB early due to change in employment or desire to pursue a pregnancy instead. A comprehensive program of nutritional and lifestyle counseling is critical to maximize overall efficacy and improve cost-effectiveness of GLP-1s for obesityParks and Rosebrough first expressed concerns regarding human safety with liraglutide as early rodent trials demonstrated an increased risk of medullary thyroid carcinoma .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.Adverse events leading to discontinuation of the study product occurred in 5 (3%) out of 199 participants in the semaglutide 2.4 mg group, 3 (3%) out of 100 participants in the semaglutide 1.7 mg group, and 1 (1%) out of 101 participants in the placebo group .Two trials have supported an increase in the risk of all types of thyroid carcinoma 200,201.In three months, Holz said, he’s shed just over 10% of his body weight, and he is enthusiastic about GLP-1 drugs not just for weight loss but for their protective effects on the heart and other potential health benefits.However, some potential additional effects beyond weight loss could hypothetically contribute to some clinical outcomes, but evidence from human studies is lacking. Although GLP-1 agonists have many positive benefits, they do have a number of potential side effects. What are the side effects of these drugs? Meanwhile, Zepbound is the same drug formulation for treatment of both obesity and/or obstructive sleep apnea. Mounjaro is the name brand of tirzepatide approved for diabetes treatment. By helping to regulate blood sugar, these medications support the management of Type 2 diabetes. Trials of all doses of liraglutide concluded that the 3.0 mg dose had the most significant weight loss results . Nausea and vomiting occurred more frequently in patients treated with liraglutide than in those treated with placebo. Another significant observation was that liraglutide reduced blood pressure at all doses and reduced the prevalence of prediabetes (84–96% reduction) at 1.8–3.0 mg per day. Those who received liraglutide lost significantly more weight than those who received a placebo or orlistat. Some advocates argue GLP-1 drugs, when combined with lifestyle interventions, should be viewed as effective long-term medical management similar to medications for other lifelong conditions like diabetes or hypertension. Average amounts of weight loss vary between specific GLP-1s based on clinical trial data. Some GLP-1 drugs only require one dose per week (semaglutide) while others need daily dosing (liraglutide). Most experts recommend combining GLP-1 drugs with improved nutrition, increased physical activity, reduced sedentary behavior, stress management and other healthy habit changes.For others who are not as sensitive to the medication, weight loss may not start until they reach higher doses.Approximately 76% of people lost more than 5% of their weight with liraglutide 3.0 mg than with placebo (30%) or orlistat (44%).The good news is that a balanced diet — that’s rich in protein and fiber, lower in fat and sugar, and includes lots of water — can help manage many of these common GI side effects.But they’re not a silver bullet — they’re a tool for the long-term treatment of obesity, to be used in conjunction with lifestyle changes like diet and exercise.Overall, a 52-week treatment duration generally allows all the GLP-1RA drugs currently studied to reach their efficacy plateaus.Not a randomized, controlled clinical trial.The GLP-RAs have also been found to affect blood pressure and cholesterol, benefiting cardiovascular health in general. What Lifestyle Changes Optimize GLP-1 Treatment? The study also measured other important secondary endpoints, including the average change in body weight and the proportion of patients whose HbA1c levels were within the predetermined ranges . In the same trial, 49.1% of participants treated with subcutaneous semaglutide experienced gastrointestinal events, compared to 26.1% of those receiving placebo; a similar proportion of patients discontinued treatment due to adverse events in both groups (2.4% for semaglutide vs. 2.2% for placebo) . The study’s results provide valuable insights into potential treatments for obesity in teenagers, although further research is necessary to confirm these findings and investigate any potential long-term effects. This drug leads to a weight loss nadir at around 36 weeks with a weight regain that happens at around 52 weeks . Much of the recommended annual weight loss diets often seen in US News and World Report reflect a variety of these dietary patterns, highlighting that diets are more than their nutrient content . The low-or very-low fat intake approach is recommended for inducing significant short-term weight loss, but its long-term efficacy is not superior to dietary interventions with higher fat content . Dietary advice historically has seen energy restriction as the foundation for weight loss. The cardiometabolic consequences of obesity such as insulin resistance, glucose intolerance, type 2 diabetes, arterial hypertension, atherosclerosis, and dyslipidemia are all stressors on the heart and vascular system 18,19. 1. Studies Completed on Tirzepatide This review synthesizes findings from studies assessing agents such as semaglutide, liraglutide, tirzepatide, and exenatide in diverse populations, including adults with and without type 2 diabetes and adolescents with severe obesity.Moreover, particular attention should be paid to the way in which prescribing doctors apply the recommendations of international guidelines in order to avoid as much as possible clinical inertia, to improve cardio–reno metabolic efficiency and safety in obese patients with or without diabetes.By helping you focus on healthy habits — exercising regularly, drinking plenty of water, and getting enough protein and fiber — it helps you mitigate side effects while maximizing health benefits as you lose weight on medication.Kessler says compounded GLP-1s, which are often cheaper than brand-name drugs and can be ordered online, carry additional risks.In medical school, greasy French fries and salted roast beef helped him stay up studying and researching late at night.Patients with T2D who require better glycemic control, want to lose weight, and are not interested in injectable medication may find oral semaglutide to be an appealing alternative .These conditions indicate the risk of developing terminal complications such as type 2 diabetes mellitus (T2DM), nonalcoholic steatohepatitis, and cardiovascular disease . Without structured nutrition care, weight loss may stall or reverse, and long-term success becomes less likely. Tailoring treatment helps people lose fat while protecting muscle and function. If we rely on a one-size-fits-all approach, we risk harming patients by promoting muscle loss or triggering nutritional deficiencies. Some patients are prone to losing lean body mass rather than fat. They help reduce appetite and support weight loss, but they are not a standalone solution. The long-term effects of GLP-1 RA use for weight loss remains an important area for future research. Recognizing obesity as a chronic disorder underscores the need for long-term pharmacological treatment, similar to the approach used for managing type 2 diabetes or hypertension to achieve optimal control.9 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. Overall, while pharmacovigilance reports have described a range of psychiatric symptoms, real-world evidence to date does not support an increased risk of suicidality with GLP-1 RAs in patients with type 2 diabetes. In this setting, prevention of weight regain may be better-termed weight loss maintenance.They help regulate appetite and improve how your body handles blood sugar.The aim was to evaluate the sustained efficacy and safety of GLP-1 receptor agonists in the long-term management of obesity.Similarly, in the STEP‐4 trial (effect of continued weekly subcutaneous semaglutide vs. placebo on weight loss maintenance in adults with overweight or obesity), individuals who stopped semaglutide treatment and started placebo regained 6.9% body weight, on average, after 48 weeks .Therefore, the final approved dosages or titration schedules for these medications may be subject to changes, which requires a cautious interpretation of the current findings.The most advanced of these pills include a form of semaglutide, the active ingredient in Ozempic and Wegovy, being developed by Novo Nordisk.It is unclear whether those without type 2 diabetes using GLP-1 for weight loss are at the same risk 197,198.Anti-obesity medications such as Contrave (bupropion/naltrexone) or Qsymia (phentermine/topiramate) also appear to be effective for maintaining weight loss . While these cosmetic findings are an issue, the loss of lean body mass is another area of concern . Patients should be aware of these potential unwanted effects and, to minimize loss of muscle mass, encouraged to participate in resistance exercises and increase protein intake . The large and long-duration GLP-1 cardiovascular outcome trials did not show an increase in pancreatitis . Despite this, animal studies have demonstrated decreases in pancreatic secretion in response to GLP-1 elevation, therefore the mechanism behind this potential interaction of GLP-1 receptor analogs and pancreatitis remains elusive . In fact, the package insert for semaglutide suggests an increase of 13% for amylase and 22% for lipase and the dual incretin agonist tirzepatide suggests a 38% increase and lipase upwards of a 42% increase . The content herein is provided for informational purposes and does not replace the need to apply professional clinical judgement when diagnosing or treating any medical condition. This site is intended for healthcare professionals Additional studies are needed to describe changes in dietary patterns and diet quality in individuals using GLP-1 or GIP/GLP-1 RAs, including macronutrient and micronutrient intake. However, those meta-analyses did not include recently published cardiovascular outcome studies (CVOT) with GLP1- RAs, which give a large additional body of data. Semaglutide demonstrated a significant decrease in BMI, with a mean reduction of −16.1% from baseline to week 68, compared to the placebo group. Semaglutide displayed more negative side effects than placebo, mostly gastrointestinal issues. It occurred in China, Hong Kong, the Republic of Korea, and Brazil, with participants receiving semaglutide or a placebo for 44 weeks. Having said that, some patients may wish to try to come off the medicine. It takes the guesswork out of healthy habits and provides you with targets for protein, fruits and veggies, hydration, and physical activity — including at least two days of resistance training. It’s important to incorporate healthy habits related to nutrition, fitness, mental health, and sleep — to maximize the efficacy of the medication, and to support your long-term health. These medications are incredibly powerful tools, but they shouldn’t be your only tool. Adults with a BMI of 25.0 to 29.9 kg/m2 are considered overweight, while those with a BMI of 30 kg/m2 or higher are considered obese. BMI is calculated as weight in kilograms divided by the square of height in meters (kg/m2) . Obesity is a chronic disease that has become a major concern in recent years, as it can have negative impacts on health, leading to increased morbidity and mortality. Those on GLP-1 medications will receive complimentary access to tailored Virtual Workshops. Ultimately, when it comes to your diet, always follow the recommendations as provided by your healthcare provider. Recent studies have raised concerns about a potential association between GLP-1 RAs and non-arteritic anterior ischemic optic neuropathy. Further research is warranted to evaluate long-term psychiatric outcomes in broader populations, including those using GLP-1 RAs for obesity or other emerging indications. As such, clinical guidelines continue to recommend against prescribing GLP-1 RAs to individuals with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2.74, 75, 76 There is growing interest in the potential neuroprotective effects of GLP-1 RAs, particularly in the context of neurodegenerative diseases. GLP-1 RAs may also have therapeutic potential in knee osteoarthritis, a condition in which excess weight exacerbates joint degeneration, inflammation, and pain. Other potential contributors to low muscle mass include fat accumulation in the muscle, mitochondrial and stem cell dysfunction, weight cycling, physical inactivity and inadequate intake of energy and protein 2,39,40. A possible contributor to muscle loss in patients with T2DM is insulin resistance, which impairs glucose uptake by muscle and can reduce its mass, strength, quality, and function . People with diabetes, for example, may have different dietary intake due to greater access to RDN intervention through diabetes self-management education and support courses. Moreover, given the vital role that protein plays in maintaining muscle health and function, the quantity and quality of protein intake is especially important to monitor. Although this review did not seek to gather all studies evaluating change in appetite perception, multiple studies appeared during the initial search which assessed patient-reported outcomes such as food cravings, emotional eating, and food preoccupation 20,21,32. A body composition scan can offer a more precise measurement. You can get a rough estimate of whether you're carrying a risky amount of visceral fat by measuring your waist circumference, Kessler says. "And that inflammatory state results in organ damage that leads to cardiometabolic disease, kidney disease, diabetes, certain forms of cancer, and potentially certain neurodegenerative changes," says Kessler. Visceral fat leeches fatty acids called adipokines or chemokines, which cause systemic inflammation in the body. However, some studies presented concerns due to factors such as post hoc analysis design, missing outcome data, or reliance on indirect measures for certain endpoints. Safety profiles were largely favorable, though gastrointestinal side effects and discontinuation rates varied by agent and dose. Some studies also highlighted the added benefits of adjunct lifestyle interventions such as exercise. GLP-1 medications have been treating type 2 diabetes since 2005—but that certainly hasn’t stopped the internet rumor mill. It’s also tough to recognize that people treat me better now that I fit into society’s accepted weight range. The mental adjustments I've had to make while living in a smaller, healthier body have been some of the most surprising aspects of this journey. "And that inflammatory state results in organ damage that leads to cardiometabolic disease, kidney disease, diabetes, certain forms of cancer, and potentially certain neurodegenerative changes," says Kessler.For the study, WashU Medicine researchers analyzed de-identified medical records in a database maintained by the U.S.For each included study, detailed data were extracted into a predesigned table.Obesity is a chronic disease that has become a major concern in recent years, as it can have negative impacts on health, leading to increased morbidity and mortality.Further research is needed to explicate the role of obesity pharmacogenomics during the weight maintenance phase.Bariatric surgery is indicated in patients with a BMI above 40 independent of coexisting comorbidities or in patients with a BMI over 35 with a history of comorbidities such as type 2 diabetes or hypertension . In conclusion, the results of this study underscore the importance of personalized, adaptable treatment strategies in obesity management. Given the current challenges of medication scarcity and insurance barriers, transitioning patients to economical AOMs emerges as a prudent alternative for long‐term weight management in addition to maintaining a healthy lifestyle. The findings suggest that, after significant weight reduction, the body's decreased inflammation and insulin resistance may enhance its responsiveness to therapies such as metformin, topiramate, phentermine/topiramate, or bupropion. But they’re not a silver bullet — they’re a tool for the long-term treatment of obesity, to be used in conjunction with lifestyle changes like diet and exercise. If you access your weight-loss medication through WeightWatchers, your healthcare provider will help you to find the appropriate maintenance dose or changes in the care plan when the time is right. Studies show that most people who come off the medicine start to regain weight, though there is a small proportion of people who don’t. Likewise, the rise of GLP-1s will shape diabetes treatment. J.P. Morgan Research forecasts the GLP-1 market will exceed $100 bn by 2030, fueled equally by diabetes and obesity usage. What’s driving the increase in appetite for obesity drugs? “The newest generations of GLP-1s and combos lead to 15–25+% weight loss on average, well above prior generations of products.” What’s whetting the consumer appetite for these weight-loss drugs, and what does this mean for sectors ranging from biotech to food? Sally: Going on a GLP-1 Helped Her Stick to a Healthy Routine 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. Glucagon-like peptide 1 (GLP-1)-based therapies, such as semaglutide and tirzepatide, represent highly effective treatment options for people with type 2 diabetes and obesity, enabling effective control of glucose and weight loss, while reducing cardiovascular and renal morbidity and mortality. Across the reviewed studies, tirzepatide, semaglutide, and liraglutide consistently led to significant weight loss over one to two years compared with placebo, and the benefits appeared to continue during ongoing treatment. Originally developed to treat diabetes, GLP-1 agonists — or obesity drugs — have risen in popularity thanks to their weight-loss effects. Although short-acting medications (such as exenatide bid and Lixisenatide) are less successful at lowering blood sugar levels throughout the night and in the morning, they continue to have a positive impact on gastric emptying when used in conjunction with basal insulin and/or long-term therapy . However, in addition to the direct effects of GLP-1 on the CNS, the incretin more likely exerts its actions on the brain through indirect pathways, that is, through vagal afferents originating in the gut and portal circulation 59,60. GLP-1 secretion from the gut seems to be impaired in obese subjects, suggesting a role in the pathophysiology of obesity . In semaglutide, Lys-26 was attached to a hydrophobic C-18 fatty di-acid moiety to bind to albumin and inhibit glomerular filtration due to its high molecular size (Figure 7). Other studies confirm the importance of dietary restraint and physical activity in preventing weight regain 247,248. These successful subjects with weight loss maintenance reported high levels of physical activity, high levels of dietary restraint, low calorie, and fat intake, and low levels of overeating (loss of control of eating or disinhibition) . When switched to placebo there was invariably weight regain, implying that the loss of inhibition of hyperphagia drove this process. Cessation of these drugs to see if weight maintenance could be achieved was largely unsuccessful (Table 3). He'd gain 20 or 40 pounds in a relatively short time frame, then slowly lose the weight, usually by going on a low-carb, high-protein diet, and exercising. In medical school, greasy French fries and salted roast beef helped him stay up studying and researching late at night. Prescribing a GLP-1 agonist may be appropriate for these patients. However, owing to the limited sample sizes of clinical trials, the low incidence of these severe adverse reactions makes them difficult to detect in small-scale studies. In clinical trials, common adverse reactions to GLP-1 class drugs include gastrointestinal symptoms such as nausea, vomiting, diarrhea, and constipation 30,31. Participants experiencing adverse reactions or poor effectiveness during the use of weight reduction medications may opt to discontinue the drug. These findings provide a reference for developing inclusion and exclusion criteria for future clinical trials on GLP-1RA drugs. In current clinical trials, the maximum administered doses of these drugs are 0.6 mg, 200 mg, 10 mg, 12 mg, 45 mg, and 2.4 mg, corresponding to 70.8 %, 66.4 %, 65.8 %, 60.7 %, 75.2 %, and 77.3 % of their respective Emax values.