Table 5 shows this subgroup of patients who completed GLP‐1 RA therapy in the MWLB and then transitioned to second‐generation AOM therapy for weight maintenance. 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 patients, 71% were treated with semaglutide 2.0 mg/week, 49% were treated with semaglutide 2.4 mg/week, 14.5% received oral semaglutide, 13% received dulaglutide, and 7% received tirzepatide (Table 3). Without an ongoing plan, weight regain is common due to metabolic and behavioral factors. Weight loss maintenance requires continued appetite control, stable metabolism, and behavioral adaptation. This highlights the need for a structured maintenance dosing strategy rather than abrupt discontinuation. Studies show that up to 70% of individuals experience weight regain within one year after stopping GLP-1 drugs. Following a comprehensive safety review, the MHRA concluded that the available data does not support a causal association between GLP-1 medicines and depression, suicidal ideation and suicide. GLP-1 medicines should not be taken by people who are breastfeeding. If you have any concerns, speak to a healthcare professional. Not all methods of birth control become effective immediately, please discuss your chosen method with a healthcare professional or consult the patient information leaflet to ensure you are effectively covered. There is only one double-blind, double-dummy, phase 3, superiority study STEP 2 that assessed the efficacy and safety of semaglutide 2.4 mg versus semaglutide 1.0 mg (the dose approved for diabetes treatment) and placebo for weight management in adults with overweight or obesity and type 2 diabetes . It is common in obesity pharmacotherapy trials that more people in the placebo group are lost to follow-up than in the active treatment group.8,10,35 Here, we aimed to investigate and compare the sustainability of the different active weight loss maintenance treatments. A total of 71% of the participants who had completed an active weight maintenance treatment (exercise, liraglutide, or the combination) participated in the post-treatment study. A substantial larger proportion of participants who had exercised compared with non-exercise were able to sustain a weight loss of at least 10%, and greater, of initial body weight one year after treatment termination. The most common medications prescribed were metformin, topiramate, bupropion, and phentermine. Overall, these findings support the use of GLP‐1 RAs followed by AOM therapy as a viable strategy for significant and sustained weight loss. In addition, the average of 4.1 provider visits within the first 12 months underscores the importance of regular follow‐up and monitoring to achieve and maintain weight loss goals. An analysis of health insurance claims released Tuesday found that most people using GLP-1 medications – about 58% – were on their treatment plan for less than 12 weeks, falling short of a key benchmark in the weight-loss treatment timeline.Therefore, we investigated whether weight loss and improved body composition are sustained better at 1 year after termination of active treatment with glucagon-like peptide-1 (GLP-1) receptor agonist, supervised exercise program, or both combined for 1 year.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).In this study, the bi-weekly GZR18 injections were generally safe and well tolerated , consistent with the known safety signals of GLP-1 receptor agonists.GLP-1s are medicines licensed to treat specific medical disorders and should only be used if you are overweight or diabetic, and not if you want to lose weight for aesthetic or cosmetic purposes.Cohorts without diabetes were characterized by exclusion of the individuals with a history of type 1 diabetes mellitus or TD2 mellitus, HbA1c ≥ 6.5% or previous treatment with glucose-lowering agents or any antiobesity medication within the past 90 days before screening .This real‐world study evaluated the efficacy of older‐generation generic antiobesity medications (AOMs) for weight maintenance after 1 year of GLP‐1 RA therapy in patients who had achieved successful weight loss.In contrast, most studies on physical activity treatment programs have reported sustained increases in physical activity levels after termination of the supervised program.With the rise in the awareness of the weight-loss benefits, GLP-1s have become very popular very quickly. The researchers also found that weight-loss medication use was higher among women than men (4.0% versus 1.7%) and higher among those of middle age (4.2% of 45 and 55-year-olds compared to 1.2% of 18-year-olds and 1.5% of 75-year-olds). These revealed that 12% of weight-loss drug users (20 out of 171) were using medication not licensed for this purpose. According to a review conducted by the European Medicine’s Agency safety committee in 2025, non-arteritic anterior ischemic optic neuropathy is a very rare side effect of semaglutide that could affect 1 in 10,000 people31. In patients with diabetes, GLP-1 RAs have been linked to an increased risk of age-related macular degeneration, although the overall risk is still low. Acute pancreatitis can be caused by gallstones or bile duct stones when they block the tubes leading from the pancreas to the stomach, which can be caused by rapid weight loss25. Changes in quality-of-life outcomes were assessed with a Danish version of the RAND 36-Item Short Form Health Survey,28 where scores in each domain range from 0 to 100, with higher scores indicating better health. If the participants did not respond to the e-mail invitation, they were contacted by phone. Group exercise consisted of vigorous-intensity indoor cycling followed by circuit training. The starting dose was 0.6 mg per day with weekly increases of 0.6 mg until a tolerated dose of a maximum 3.0 mg per day was achieved. As demonstrated in Table 4, the average BMI decreased significantly at 12 months compared to the initial visit, remained about the same at 18 months, and again remained about the same at an average of 576 ± 20.2 days (after initial visit) at the patient's follow‐up visit, indicating that the severity of obesity had decreased. Furthermore, it can alter the gut microbiome and can induce expression and secretion of growth‐differentiating factor 15, which reduces food intake, body mass, fasting insulin, and glucose intolerance 11, 12. This follow‐up appointment was, on average, 166 days (5.5 months) after the most recent visit in the bundle program when the patients were on GLP‐1 RAs. Although some weight regain was observed by 24 months, the difference in weight reduction between 18 months and 24 months was not statistically significant. “I have seen more significant gastrointestinal side effects with oral semaglutide than with injectable,” Moreno said, noting that he wonders “what differences in side effects may occur when using such high doses of semaglutide compared with the injectable dose.” But Novo Nordisk declined to say whether it’s filed for approval of the drug from the US Food and Drug Administration, and sales of an oral form of semaglutide for type 2 diabetes, approved as Rybelsus, have been dwarfed by those of injectable Ozempic. But she and other doctors also warn about the potential for misuse, a problem that could become more pervasive with daily pills instead of weekly injections; they could make it easier to take more than recommended or to share medication inappropriately. “This has been really challenging,” Holz, 44, said about a week into treatment. Jared Holz thought about taking one of the new GLP-1 drugs for weight loss for months before he actually filled the prescription. 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.Reasons for participants not completing the low-calorie diet and 52-week intervention have been published previously.7All authors contributed to subsequent drafts and interpretation of data.Therefore, we investigated the sustainability of exercise-based and pharmacology-based single or combination treatment for weight loss maintenance in a real-world situation.Understanding the role of maintenance dosing, its benefits, and how to adjust it for individual needs is key to ensuring lasting results.Clinicians should discuss the benefits, risks, and cost‐effectiveness of transitioning from expensive GLP‐1 RA medications to oral generics. 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. These results are noteworthy as many patients lose insurance coverage for GLP‐1 RAs and are concerned about weight regain off the medications. This demonstrates that alternative and inexpensive medications can be used for weight maintenance if GLP‐1 RA therapy cannot be continued. Additionally, from the last visit at our obesity center (around 14 months) and the most recent follow‐up appointment at another provider's office within the health system (when the patients were not on GLP‐1 RAs), there was still a mean 1.46 lb decrease in weight noted using older‐generation generic AOMs. “It’s really important to not use the scale as the only outcome of whether you should stay on this medication. And experts warn that the GLP-1 treatment process can be different for everyone. But the new report suggests that the real-world efficacy is not as promising as clinical trial data would suggest. Another new report supports the claim that the benefits of GLP-1s are extended with long-term, consistent treatment. But using GLP-1 treatments are still an investment in many ways. But as long as kidney function is normal, she suggests her patients on a GLP-1 aim to eat 100 g of protein a day, with 60 g of protein as the minimum. The amount of protein you will need depends on your weight, says Troutman. Curbing muscle loss will involve incorporating high-protein foods into your diet as well as resistance exercises into your daily routine. Without a structured approach, individuals may struggle to keep off the weight they worked hard to lose. GLP-1 receptor agonists have emerged as a groundbreaking medical intervention for effective weight reduction, but discontinuing them often leads to weight regain. This site is an advertisement for services and not any specific medication. I love it when people see me today and they're like, “whoa, what happened to Terry? If you get a lump or swelling in your neck or an allergic reaction, serious side effects may happen, including pancreatitis. You know, when I started to take Wegovy®, I started a weight log and uh, over time, man, you could really see those results. 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. Today, many of the GLP-1s are approved to treat weight loss, and it has practically become their primary indication. 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). Finding the right medication often requires patience and close work with your healthcare provider. If you have questions or concerns about your health, please talk to your doctor. The information provided on this website is for informational purposes and not a substitute for professional medical advice, diagnosis, or treatment. Connect with us for a journey towards a healthier, more vibrant life. Our commitment to excellence and compassion in healthcare drives us to continuously improve and expand our services. This section collects any data citations, data availability statements, or supplementary materials included in this article. However, the coexistence of diabetes has been consistently related with less weight loss under medication than in patients without diabetes. Moreover, people with diabetes may have had obesity for longer and may be less adherent to exercise, which seems to potentiate the effects of GLP-1 RA. The approval of once daily liraglutide, 3.0 mg, and once weekly semaglutide, 2.4 mg, for chronic weight management provides a novel effective strategy against obesity. GLP-1 medications have transformed the landscape of weight loss and metabolic health. The addition of supervised exercise to obesity pharmacotherapy seems to improve healthy weight maintenance after treatment termination compared with treatment termination of obesity pharmacotherapy alone. The primary outcome of the post-treatment assessment was change in body weight from after the initial weight loss (at randomisation, week 0) to one year after treatment termination (week 104) in the intention-to-treat population. However, long-term adherence in a real-world setting is challenging, and termination of obesity medication results in weight regain towards pre-treatment body weight. Mayo Clinic Improves the Mediterranean Diet for Everyday Americans An average person starting GLP-1 medications for weight loss have been cited as averaging approximately 2.3% of their body weight in this same period. This aligns with Mayo Clinic research showing that while "tirzepatide and semaglutide are the most effective for weight loss," different medications work better for different people. However, higher levels of weight loss of ≥ 15% were achieved almost exclusively by participants with diabetes who received liraglutide or semaglutide, whereas this outcome has not been attainable by any other glucose-lowering intervention or with lifestyle intervention alone. First, the concomitant medications that promote weight gain including sulfonyureas, insulin, beta-blockers and the fear of hypoglycaemia inherently related to the treatment of diabetes presumably reduce the efficacy of anti-obesity pharmacotherapy in diabetics. It was previously noted in trials of other anti-obesity medications that people with diabetes have more difficulty losing weight than individuals without diabetes, and differences between individuals with and without diabetes were consistently confirmed also for GLP-1RAs. “For some patients, they need to stay on the same dose and regimen. It would be rare for someone to continue the medicine if they are experiencing enough vomiting and diarrhea to lose excessive amounts of weight,” says Davisson. “Once someone is at the highest dose in six months, they typically continue to lose weight for the rest of the year and maybe beyond that, but there are always exceptions to the rule.” It takes at least six months for someone to get to the maximum dose of Zepbound, for example, and longer for those who have more side effects. Insurance plan copays may have affected cost considerations, but the individuals in this analysis were not paying out-of-pocket for their treatment. Social drivers of health – transportation, access to food, socioeconomic status – all of that also makes a difference.” “Wraparound support services really make a difference – whether a person has lifestyle support management, nutrition, diet and side effect management,” Hashmi said, and “health equity matters. Each additional follow-up visit increased a patient’s chances of staying on the treatment by 60%, said Dr. Razia Hashmi, vice president of clinical affairs for the Blue Cross Blue Shield Association. All individuals of child-bearing potential (who are able to become pregnant) using GLP-1 medications should take steps to ensure they do not become pregnant. Switching without medical advice may increase the risk of experiencing side effects or make the treatment less effective. We have had reports of people experiencing severe side effects from fake GLP-1 medicines. Please find further advice for patients and the public on treating obesity on the NHS website. In the UK, there are several licensed GLP-1 medicines including semaglutide (sold under the brand names Wegovy, Ozempic and Rybelsus), tirzepatide (Mounjaro) and liraglutide (sold under various brand names). Of these 69 patients, 40 patients were transitioned to generic second‐generation AOMs after the MWLB ended (Table 3). As shown in Table 3, 69 of 105 patients received GLP‐1 RA therapy specifically during the MWLB for 12 months. These patients were placed on oral metformin, topiramate, bupropion, naltrexone monotherapy, or combination; phentermine was avoided in many cases due to its controlled substance designation upon transition to primary care. A total of 69 patients finished 12 months of GLP‐1 RA therapy and the 6‐month transition period. I love it when people see me today and they're like, “whoa, what happened to Terry?This site is an advertisement for services and not any specific medication.A full list of the known side effects can be found in the product information for the individual medicines.Drugs approved for weight management provide sufficient mean and categorical change in body weight .But the data up until now shows that stopping GLP-1 medications, regardless of which drug in the class is being used, often leads to the patient eventually gaining back much of the weight they’ve lost even if they maintain a healthy diet and lifestyle.Patients were AOM naïve prior to the initial medical obesity assessment visit."Early weight loss may be a signal that you can be successful with lifestyle alone," said Dr. Donald Hensrud, M.D., M.S., the medical editor of The Mayo Clinic Diet.This suggests that these patients were able to maintain weight loss on generic second‐generation AOMs.This guideline is a key deliverable under the WHO acceleration plan to stop obesity and will be updated regularly as new evidence emerges. GLP-1 weight loss timeline: month by month 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. The downside of any weight-loss medication is that as soon as the patient stops it, frequently the weight will start coming back, regardless of what else the patient is doing to mitigate it. While the drugs themselves haven’t shown that they improve fertility, they can help with weight loss, which will at least help remove that comorbidity. 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. The MHRA advises patients on all GLP-1s to use contraception while taking GLP-1 medicines (including an additional barrier method for patients starting or increasing tirzepatide who are using oral contraception), as well as for a defined “wash-out” period afterwards before trying to get pregnant (see Figure 3). There are not enough data to determine the impact of GLP-1 medicines on human pregnancies but, in some animal studies, GLP-1 medicines were found to be harmful to the unborn foetus32. For liraglutide, there were 137 reports of acute and chronic pancreatitis made to the MHRA’s Yellow Card scheme between 2020 and 2025, one of which had a fatal outcome24. GLP-1s have previously been suggested to be linked to self-harm and suicidal thoughts, but the MHRA concluded in September 2024 that the available data do not support a causal association between GLP-1s and depression, suicidal ideation and suicide, following a review by the European Medicines Agency’s pharmacovigilance risk assessment committee19. All studies included lifestyle modifications as part of the protocol; one study with liraglutide and one study with semaglutide included additional dietary restrictions and intensive behavioural therapy 13, 16.The mean weight loss difference between GLP-1 RAs and placebo in patients with diabetes was 4–6.2% compared to 6.1 up to 17.4% in individuals without diabetes.“Once someone is at the highest dose in six months, they typically continue to lose weight for the rest of the year and maybe beyond that, but there are always exceptions to the rule.”Gastrointestinal side effects make up around half of the side effects reported to the MHRA via the Yellow Card Scheme for tirzepatide, semaglutide and liraglutide between 2020 and 2025 (43,475 out of 78,171 side effects; see Figure 2)18.Glucagon-like peptide-1 receptor agonists (GLP-1s or GLP-1RAs) are medicines that help people feel fuller by mimicking a natural hormone released after eating.An off-treatment extension of a study of semaglutide, a receptor agonist of the incretin glucagon-like peptide-1 (GLP-1), showed that about two-thirds of the lost weight was regained within the first year after treatment termination.Semaglutide resulted in 10.3–17.4% difference in mean weight compared to placebo 15–17, 19. 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. It’s possible to still lose more weight through more traditional diet and lifestyle interventions. Panel A shows the estimated mean changes in body-fat percentage during a low-calorie diet (week −8 to 0), a weight maintenance intervention (week 0–52) with placebo, exercise plus placebo, liraglutide, or the combination of exercise and liraglutide, and a post-treatment phase (week 52–104). More participants who had received exercise had a weight loss of at least 5% of initial body weight compared with liraglutide (OR 2.9; 95% CI, 1.3; 6.6) and at least 10% compared with placebo (OR 3.7, 95% CI, 1.2; 11.1). This real‐world study evaluated the efficacy of older‐generation generic antiobesity medications (AOMs) for weight maintenance after 1 year of GLP‐1 RA therapy in patients who had achieved successful weight loss. In addition to its core healthy weight loss program, The Mayo Clinic Diet also offers tailored programs for people with heart disease or diabetes, and those taking weight-loss medications. Furthermore, one-third of the study’s participants who took the weekly semaglutide lost at least 20 percent (an average of 46 pounds) of their body weight by the end of 15 months. Patients with diabetes were enrolled in a phase 3a SCALE Diabetes trial and phase 3b SCALE Insulin trial . Both critera were met in phase 2 study , SCALE Obesity and Predabetes and SCALE Maintenance trials. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Efficacy and safety of these drugs have been proven for a representative sample of patients with different comorbidities, from the various demographic, ethnic and racial groups . Individuals with BMIs ≥ 30 kg/m2 or ≥ 27 kg/m2 in the presence of comorbidities including type 2 diabetes, hypertension, dyslipidaemia, sleep apnoea and/or cardiovascular disease were identified as appropriate candidates for such pharmacotherapy . The reliable models that might predict weight reducing potential at the individual level have not been identified yet. Connecting you with expert guidance and affordable treatments, delivered directly to your door. A well-structured GLP-1 maintenance strategy involves gradual dose adjustments, regular monitoring, and lifestyle integration. At 18 months, they maintained the weight loss, with a mean BMI of 27.9 kg/m2. Despite advances in treatment over the last 50 years, obesity and T2D continue to be rapidly growing drivers of morbidity and mortality in the 21st century. About Fractyl HealthFractyl Health is a metabolic therapeutics company focused on pioneering new approaches to the treatment of metabolic diseases, including obesity and T2D. Revita is being studied in an ongoing IDE-approved pivotal trial to evaluate its potential safety and efficacy in post-GLP-1 weight maintenance. Participants were initially recruited for the weight loss and weight loss maintenance phases of the study (week −8 to 52). To investigate the sustainability of the different weight maintenance treatments in a real-world setting, there was no contact between study participants and study personnel until the invitation to participate was sent by e-mail near completion of the second year. The results of the first two phases, i.e., the weight loss (week −8 to 0) and weight maintenance (week 0–52) phases, have been published previously,7,26,27 and the results of this paper are based on the post-treatment phase alone (week 52–104) and in combination with the weight maintenance phase (week 0–104). Figure 3: How many months should GLP-1s be stopped before a pregnancy? Protocols with cohorts with diabetes included an algorithm for the reduction or withdrawal of other antidiabetic drugs for patients who lose clinically significant amounts of weight. Semaglutide resulted in 6.2% difference in mean weight loss vs. placebo . The proportion of subjects who lost ≥ 5% of baseline body weight was 86.4–88.7% 15–17, 19. Notably, SCALE Insulin trial explored the antiobesity efficacy of liraglutide in diabetics treated with basal insulin that has well-established weight gain potential . The proportion of subjects who lost ≥ 5% of baseline body weight was 50.5–73% 10–14, 19. Using GLP-1 medicines around the time of a surgery or an operation SST, SBKJ, and SM contributed to the design of the post-treatment study. For all treatment groups, those who attended the post-treatment study had a better mean treatment response during the active treatment than those who did not attend. Overall, the loss to follow-up rates in our study were similar to other post-intervention follow-up studies of exercise and long-term pharmacological interventions.13,40,41 The inclusion of a one-year post-treatment phase with no active intervention reflects a real-world setting and is important in the evaluation of obesity treatments due to the relapsing nature of obesity. Other outcomes related to metabolic health were changes from week 0 to 104 in fat mass, lean mass, waist and hip circumferences, HbA1c, fasting glucose, systolic and diastolic blood pressure, resting heart rate, and plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. This outcome was chosen since both effects on treatment and off treatment are important to evaluate the sustainable benefits in a real-world setting. Total body-fat and lean mass (dual-energy x-ray absorptiometry, Hologic Discovery), HbA1c, lipid levels, and self-reported quality of life were measured at weeks −8, 0, 52, and 104. Body weight, hip and waist circumferences, fasting glucose levels, blood pressure, and resting heart rate were measured in the fasted state before the low-calorie diet (week −8), at randomisation (week 0), at weeks 4, 13, 26, 39, 52 after randomisation, and one year after intervention completion (approximately 104 weeks after randomisation). Participants not allocated to exercise were encouraged to maintain habitual physical activity during the 52-week intervention period. This time period was chosen because it coincided with activation of 12 months of obesity pharmacotherapy benefits (including GLP‐1 RA therapy) for patients enrolled in the MWLB at our institution, and weight measurements beyond 12 months would likely be assessable for these patients. MWLB patients were transitioned to a “weight maintenance phase” if they had achieved a target clinical goal of 2 with documented stability of weight without regain over 3 to 6 months. Given the recent FDA approval of novel GLP‐1 RAs and the consequent scarcity of long‐term efficacy data, we initiated a prospective real‐world cohort study among our program participants. This shift underscores the importance of an in‐depth analysis of the posttreatment phase to refine a predictive value‐based model that accurately reflects sustained weight loss results. In future, we encourage further research into individualisation of pharmacotherapy of obesity by exploring the differences in the weight loss by sex, race, concomitant therapies, effect of altered microbiota and genetic background. It is established that people with diabetes have more difficulty losing weight than individuals without diabetes and differences between individuals with and without diabetes were consistently confirmed also for GLP-1RAs. Bariatric surgery is the most effective antiobesity management strategy characterized by average of 30–40% weight loss, but it comes at a cost of irreversibility, surgery-related complications and considerable percentage of late complications . The principal goal in obesity management is clinically significant weight loss defined as a long-term reduction in fat mass with a goal to reduce morbidity and mortality through quantifiable improvements of biomarkers . The use of supplements, concomitant medication, and treatments for obesity (e.g., pharmacotherapy) were recorded. During the one-year post-treatment phase, none of the interventions were continued, and participants had neither restrictions nor encouragement in terms of weight management strategies. At week 52, the supervised exercise program was terminated and participants returned the sports watches and heart rate monitors. In this study, the bi-weekly GZR18 injections were generally safe and well tolerated, consistent with the known safety signals of GLP-1 receptor agonists. 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. Having a trusted, evidence-based resource to connect you to the latest best practices and recommendations and offer quick links to patient education articles is essential for professionals navigating the complicated landscape of GLP-1 medications. 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. The Importance of GLP-1 Maintenance Dosing for Long-Term Weight Management This guide explores the science, clinical guidelines, and patient-centered strategies for using GLP-1 receptor agonists as a long-term weight management tool. This is where maintenance dosing plays a crucial role. However, despite their proven effectiveness, weight regain is common after discontinuation. GLP-1 receptor agonists have transformed the weight management landscape by targeting hunger regulation, insulin sensitivity, and gastric emptying. Obesity is a chronic and complex disease, significantly increasing the risk of metabolic disorders such as type 2 diabetes, hypertension, and cardiovascular disease. 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. This is because there is not enough safety data to know whether taking a GLP-1 medicine can cause harm to the baby. A full list of the known side effects can be found in the product information for the individual medicines. However, compliance and adherence dropped significantly at the 24‐month mark, with only 4.7% of the patients following up with either an obesity provider or a primary care physician. Of note, this includes all patients who received 12 months of AOM therapy, regardless of treatment completion or type (novel GLP‐1 RA therapy and/or older generic options). However, upon transition to primary care, for weight maintenance, phentermine was avoided due to its controlled substance designation. The utilization of GLP‐1 RAs was greater than 100% as more than one GLP‐1 RA was used for an individual patient; this was done due to medication shortages, decreased efficacy, or side effects. Informatics identified a total of 105 patients who achieved BMI 2 after 12 months on treatment with AOMs during the MWLB. Differences in the efficacy of liraglutide 3.0 mg and semaglutide 2.4 mg in the weight management of patients with type 2 diabetes Differences in the efficacy of liraglutide 3.0 mg and semaglutide 2.4 mg in the weight management of patients without type 2 diabetes Figure 3 demonstrates the proportion of patients with ⩾ 5% of weight loss from baseline for liragutide and/or semaglutide vs. placebo. 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. It’s a field that’s already undergoing a revolution, with millions of people across the US now using semaglutide and tirzepatide, sold as Wegovy and Zepbound for weight loss (and for diabetes as the better-known Ozempic and Mounjaro). Related article Popular weight-loss and diabetes medications show promise for curbing smoking, study suggests Another limitation of this study is that it did not capture lifestyle modifications, including the patients' nutritional intake, exercise, sleep quality, emotional state, or stress level experienced in the weight maintenance phase, which could have also confounded the results. This prospective real‐world study demonstrates that patients treated with GLP‐1 RA therapy for 12 months who achieved BMI 2 and then transitioned to cost‐effective alternative AOMs were able to lose 25.1% ± 2.6% of their body weight, on average, and maintain the weight reduction up to 24 months. Users start with a low dose of these medications and gradually increase it over time until they reach a targeted dose. You may see them referred to in the media as “weight loss injections” or “skinny jabs” but not all of these medicines are authorised for weight loss. Our latest Best Practices in Healthcare survey offers fresh insights into how employers are approaching coverage of GLP-1 therapies for weight loss. While GLP-1 therapies represent the first efficacious treatment option for adults with obesity, the WHO guideline emphasizes that medicines alone will not solve the problem. I got assigned a wonderful health coach and I'm still in touch with her today. Wegovy® should not be used with other semaglutide-containing products, other GLP-1 medicines or in children under 12 years of age. We went over the potential benefits and risks of treatment. My body just wasn't responding and I was just stuck at 400 pounds and I was like, I'm gonna be this big forever. She did a thorough workup and told me most of my challenges were due to my weight. 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. Before a patient leaves the pharmacy with their GLP-1 medication, it is important that they are completely comfortable with how to take it. It is important, however, that they are aware that severe vomiting or abdominal pain may be a sign of pancreatitis and will require immediate attention from their healthcare provider. Injectable semaglutide also has an indication for cardiac risk reduction, and many presume approval for cardiac indications for other GLP-1 medications is only a few years away. This made GLP-1s a safer option compared to a lot of the other drugs being used that were only causing patients to push more insulin out and causing weight gain without addressing many of the issues surrounding the core condition of diabetes. GLP-1 medications have become wildly popular to treat obesity. As Dr. Meghan shows, success comes from understanding and working with your body's individual response to these powerful medications. Understanding how your medications interact leads to an important timeline most people don't know about. However, with significant weight loss, particularly a combination of healthy dietary modifications, GLP‐1 RA therapy, and an increase in physical activity, there is a reduction in fatty acid mobilization and uptake, which is a key process in reducing insulin resistance.Reasons for participants not attending the post-treatment study are shown.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 .HydroBelle hydration sticks offer gentle electrolytes that support your body as it adjusts.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.When working with GLP-1 medications, providers need to stay aware of issues related to shortages and potential therapeutic substitutions.Multimodal approaches combining peptides targeting receptors at different levels might therefore be of significant additional benefit in particular in patients with diabetes.Providers need to use every opportunity to make sure patients understand and are comfortable with this concept. GLP-1 medications and weight loss: Helping patients navigate beyond the trends These findings suggest Revita may help people stay at their target weight or lose additional weight, even after discontinuing GLP-1 drugs, offering a potential path to durable, drug-free weight maintenance. “There may be some direct benefits of the medication in the absence of significant weight loss, which is also why you should be talking to your doctor at length about why you’re using this medication.” And although most prescriptions came from primary care physicians, those who were prescribed GLP-1s by endocrinologists or others with expertise in weight management were more likely to reach at least 12 weeks of continuous treatment. Findings from the Blue Cross Blue Shield data emphasize the important role that providers can play in helping patients stick with their treatment with GLP-1s. Earlier this month, data presented at the European Association for the Study of Diabetes conference showed that study participants who got a higher dose of the experimental drug amycretin lost an average of 13% of their body weight in 12 weeks. An analysis of health insurance claims released Tuesday found that most people using GLP-1 medications – about 58% – were on their treatment plan for less than 12 weeks, falling short of a key benchmark in the weight-loss treatment timeline. VESPER-3 is an ongoing 64-week, randomized, double-blind, placebo-controlled study in participants with obesity or overweight without type 2 diabetes. After 30 weeks of treatment, compared to the placebo group, participants receiving different doses and frequencies of GZR18 injection (12 mg, 18 mg, 24 mg, and 48 mg Q2W; 24 mg QW) had a significant reduction in the percent change in body weight from baseline. (1) to demonstrate PF’3944 could achieve continued weight loss when switching from weekly to monthly subcutaneous injections and maintain its efficacy while reducing the dosing frequency four-fold; and (2) to demonstrate PF’3944 could switch to a four-fold equivalent monthly dose while maintaining a well-tolerated and favorable safety profile. Belle connects patients with licensed providers who determine treatment plans based on individual health needs. If you’re starting GLP-1 or GLP-1/GIP medication for weight loss, you’re probably wondering GZR18 injection, independently developed by Gan & Lee, is a once-weekly or potential bi-weekly GLP-1 receptor agonist intended for the treatment of T2DM in adults and for weight management in obese/overweight individuals. The study assessed changes from baseline in average weight, waist circumference, waist-to-hip ratio, body mass index (BMI), glycemic parameters, and the safety and tolerability of the drug. In addition, these medications have demonstrated improvement in weight‐related comorbidities, such as type 2 diabetes, fatty liver, hyperlipidemia, hypertension, sleep apnea, cardiovascular disease, and joint pain. FDA Breakthrough Device designation in weight maintenance for people with obesity who discontinue GLP-1 based drugs. We are encouraged by the consistent and robust signal of weight maintenance observed in this study, and these results strengthen our confidence in Revita’s potential and raise anticipation for the randomized data from the REMAIN-1 Midpoint Cohort expected in the third quarter. GLP-1 Weight Loss Drugs: Coverage Under Medicaid and Other Health Plans 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. Most notably, many patients will complain that they don't feel hungry anymore. It’s also helpful to review patient education materials to share with your patients and plan members. Between Dec 17, 2018, and Dec 17, 2020, 109 participants attended the post-treatment study.Wegovy® goes beyond weight management for adultsRather, it will likely become a long-term tool — in addition to a nutritious diet, adequate exercise, and proper hydration — for weight management.Additionally, GLP-1 medications have not been routinely studied in pregnant people or for their effects on fetuses.In North Carolina, the state employee health plan initiated coverage of GLP-1s for weight loss purposes in 2015.However, in real-world settings, up to half of those who initiate incretin-based therapy, have discontinued treatment within the first year.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.Acute pancreatitis can be caused by gallstones or bile duct stones when they block the tubes leading from the pancreas to the stomach, which can be caused by rapid weight loss25. Availability may vary depending on your location and whether treatment is for diabetes or for weight loss. The combined multimodal peptides that target GLP1-GIP receptors, will provide even more effective treatment than currently approved GLP-1 RA, in particular in patients with diabetes where the pathophysiology of obesity seems to be even more complex than in individuals without diabetes. Moreover, severely altered microbiome in patients with obesity and diabetes as well as a genetic background that predispose to weight gain in this population might also be considered as potential contributors . Second, a decrease in glycusoria and subsequently less weight loss in patients with diabetes might also contribute the population-based difference in efficacy. Proportion of patients with ≥ 5% weight loss from baseline for liragutide and/or semaglutide vs. placebo.Consequently, the findings may not fully represent the diverse population affected by obesity.Panel D shows a bar graph of the percentages of participants who had a weight loss at week 104 of at least 5%, 10%, 15%, and 20% of initial body weight (at week −8).The dose for weight loss is 25 to 50 milligrams a day, compared with 14 milligrams for Rybelsus and a maximum of 2.4 milligrams a week for injections of Wegovy.Data also show that more than 400,000 items of tirzepatide and semaglutide were dispensed on the NHS in October 20251.Availability may vary depending on your location and whether treatment is for diabetes or for weight loss.But she and other doctors also warn about the potential for misuse, a problem that could become more pervasive with daily pills instead of weekly injections; they could make it easier to take more than recommended or to share medication inappropriately.In addition, it has not been investigated whether incorporating exercise together with GLP-1 receptor agonist treatment can improve the sustainability of healthy weight loss maintenance after treatment is terminated.As shown in Table 3, 69 of 105 patients received GLP‐1 RA therapy specifically during the MWLB for 12 months. Not only does buying from unregulated sellers expose people wanting to lose weight to serious health risks – it is also against the law to sell these medicines in this way. 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. 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. We also need to improve the ability to identify patients who respond better to weight loss and can lose at least 15% of their weight. “There is an extraordinary unmet need in obesity treatment, which is the ability for patients to stop GLP-1 drugs without regaining weight. All participants had previously been treated with a GLP-1 therapy for durations ranging from approximately 5 months to 3 years, with a median total body weight (TBW) loss of 20.9% while on therapy. The data from Dandelion Health showed that the 10% of people with the best response to GLP-1s had results that mirrored what clinical trials found, but the 10% with the least success with the treatments had no weight change, or even an increase in weight, over time. The process to develop the guideline involved extensive analysis of available evidence, and consultation with a wide range of stakeholders, including people with lived experience. WHO developed the guideline in response to requests from its Member States looking to address the challenges posed by obesity. Without deliberate policies, access to these therapies could exacerbate existing health disparities. The guideline emphasizes the importance of fair access to GLP-1 therapies and preparing health systems for use of these medicines. Obesity is a complex, chronic disease and a major driver of noncommunicable diseases, such as cardiovascular diseases and type 2 diabetes and some types of cancer. Gastrointestinal side effects make up around half of the side effects reported to the MHRA via the Yellow Card Scheme for tirzepatide, semaglutide and liraglutide between 2020 and 2025 (43,475 out of 78,171 side effects; see Figure 2)18. The New Mayo Clinic Diet has been designed to help participants make lasting, meaningful changes to their behavior so they can lead a healthier life. "Early weight loss may be a signal that you can be successful with lifestyle alone," said Dr. Donald Hensrud, M.D., M.S., the medical editor of The Mayo Clinic Diet. This weight loss was also shown to be maintained at 12 months. The analysis offers hope that significant weight loss can be achieved when GLP-1s aren't an option. Phentermine/topiramate, metformin, bupropion, and naltrexone can also improve insulin sensitivity by facilitating calorie restriction by decreasing hunger, thereby promoting weight loss over time. A decreased obesity severity represents a decrease in adiposity; this corresponds to a decrease in treatment intensity. Metformin has been shown to helpful in weight loss by improving insulin resistance and promoting appetite suppression through increased secretion of GLP‐1 and peptide YY and increased hypothalamic leptin sensitivity 9, 10. A total of 40 individuals were given therapy with GLP‐1 RAs for 12 months and then were transitioned to older‐generation generic therapy (phentermine, generic phentermine/topiramate, topiramate, metformin, bupropion, and/or naltrexone) to assist with weight loss maintenance after the MWLB ended. 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. Antiobesity pharmacotherapy included FDA‐approved agents (phentermine, phentermine/topiramate, naltrexone/bupropion, semaglutide, and tirzepatide) or off‐label therapies (semaglutide and tirzepatide injections approved for type 2 diabetes, oral semaglutide, topiramate, bupropion, and metformin). Some patients may lose 5–10% of their weight in 3–6 months, while others may achieve 20%+ over a year. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. SBKJ and LMO contributed to the practical conduction of the post-treatment study. SBKJ, LMO, RMS, CRJ, JRL, and CJ contributed to data collection of the S-LITE study. After the medical weight loss bundle, 40 patients transitioned to generic AOMs. A pivotal study of Revita in patients with obesity after discontinuation of GLP-1 based drugs, called REMAIN-1, was initiated in the third quarter of 2024 and enrollment is now complete. If these findings are sustained beyond 3 months and validated in the randomized cohort, this could become a viable solution for the many patients who would like to stop GLP-1 medications but currently can’t.” This cohort serves as an early clinical window into Revita’s potential to support durable weight maintenance following GLP-1 discontinuation, a period of time when patients are typically vulnerable to rapid weight regain. The combination of these effects leads to sustained and significant weight loss, especially when combined with diet and lifestyle changes. Therefore, focused continued physical activity after the termination of pharmacotherapy is advisable for healthy weight maintenance. Participants who previously received the combination treatment had improved scores of physical functioning, less limitations due to physical health, and energy/fatigue compared with liraglutide alone. If there are any trials or treatments we have missed, please get in contact to let us know. This off-label use is corroborated by the ongoing ‘Smoking Toolkit Study’, which added questions around weight-loss jabs to its representative monthly surveys in January to March 2025 (5,893 total respondents). Concerns have been raised about patients accessing GLP-1s inappropriately; for instance, when they do not meet BMI eligibility criteria. Experts have stressed the “multi-factorial” causes of obesity and therefore the need for a multi-faceted approach, considering other factors like lifestyle, trauma and psychological support35. There is little clinical guidance on this, so pharmacists must prioritise patient safety and, since there is no validated dose equivalence, the safest approach is to start the new medication its lowest available dose then titrate gradually per standard schedule. You've seen the headlines about dramatic weight loss results with GLP-1 medications. We use only trustworthy sources, including peer-reviewed research, certified health and weight loss experts, people with lived experience, and information from top institutions. It’s best to talk to your doctor about what a healthy weight loss timeline will look like for you, and to make sure you’re eating enough — especially high-protein foods — while on a GLP-1 medication. A reasonable weight loss rate is typically losing 10 percent of your body weight over the course of six months. In my experience, patients who continue to have such symptoms beyond a couple of weeks will not stay on the medicine. GLP-1 medication impacts the gut, so common side effects include nausea, vomiting, worsening acid reflux, diarrhea or constipation, and stomach discomfort or cramping. If weight loss slows down, a doctor may increase the dosage. GLP-1 medications require slow-dose titration, says Davisson. Additionally, GLP-1 medications have not been routinely studied in pregnant people or for their effects on fetuses. But should a patient using a GLP-1 plan to become pregnant or become pregnant, they must be counseled to stop the medication as soon as possible because weight loss medications are not recommended during pregnancy, according to the American College of Obstetricians and Gynecologists and other groups. Because people who are overweight or have obesity may have trouble getting pregnant, providers will often encourage weight loss to help with infertility. The cases in which low sugar would be a concern would be in patients with pre-diabetes, or in patients taking other diabetes medications that do increase the risk of low blood sugar. Many patients experience relatively benign side effects, like an upset stomach or nausea, when they first begin the medication, and that may subside over a few weeks. Most, but not all, studies on physical activity treatment programs have reported small, sustained increases in physical activity levels after termination of the supervised program.20, 21, 22, 23, 24 These studies are heterogeneous regarding duration, physical activity intervention, degree of supervision, and study population. In contrast to pharmacotherapy, exercise is a low-cost intervention and represents a behavioural change that, in principle, can be continued in a real-world setting after termination of the supervised treatment. Weight regain during the one-year post-treatment phase was 6 kg larger after GLP-1 receptor agonist treatment compared with after supervised exercise. We conducted a post-treatment study in extension of a randomised, controlled trial in Copenhagen. Common medications can secretly fight against your GLP-1 treatment. Dr. Meghan Garcia-Webb, a Boston-based physician board-certified in Internal Medicine, Lifestyle Medicine, and Obesity Medicine, has guided hundreds of patients through their GLP-1 weight loss journeys. This will help support healthy weight loss without risking your health and well-being. The speed of weight loss that occurs on a GLP-1 medication is largely dependent on the individual. Each person will respond to treatment differently and assess the balance of costs and benefits to their heath differently. “If you don’t have frequent touchpoints, frequent interactions, then it’s really it’s hard to manage side effects. Only about two-thirds of adults who have used injectable weight-loss drugs say they feel that they were effective, according to a new KFF poll. Studies have shown lower risk of obesity-related cancers, too. These data points reflect growing interest, tempered by cost concerns, as employers weigh the value and sustainability of GLP-1 coverage. Reasons for participants not completing the low-calorie diet and 52-week intervention have been published previously.7 In this article, we report the results of a post-treatment study conducted in extension of a randomised, controlled trial.7 The study was conducted at the Department of Biomedical Sciences, University of Copenhagen, and the Department of Endocrinology, Copenhagen University Hospital—Hvidovre. It is, therefore, not established whether people who have completed a long-term exercise program remain more physically active in real-world settings after termination of the supervised program. In the logistic regression analyses, for all participants who had missing body weight data at week 104, we used the predicted body weight value from the linear mixed model to calculate changes from week 0 to 104. The primary outcome of the study was the change in body weight (kg) from randomisation to one year after termination of the weight maintenance intervention (week 0–104). All participants who had undergone randomisation were invited to participate in the post-treatment study, which was composed of a set of outcome assessments one year after the planned completion of the 52-week weight maintenance intervention. In addition, it has not been investigated whether incorporating exercise together with GLP-1 receptor agonist treatment can improve the sustainability of healthy weight loss maintenance after treatment is terminated. While some patients with diabetes achieved ≥ 5 or 10% with placebo, higher levels of ≥ 15% in patients with diabetes were achieved almost exclusively with those who received liraglutide or semaglutide and not by those on placebo 20–22. In patients with diabetes, both efficacy benchmarks were achieved by semaglutide , while the efficacy of liraglutide did not meet the criteria in mean difference between active product vs. placebo 20, 21. Proportion of patients with ≥ 5% weight loss from baseline for liragutide and/or semaglutide vs. placebo. Changes of mean body weight from baseline for liragutide and/or semaglutide vs. placebo More participants who had previously received combination treatment maintained a weight loss of at least 10% of initial body weight one year after treatment termination (week −8 to 104) compared with participants who had previously received placebo (odds ratio OR 7.2 2.4; 21.3) and liraglutide (OR 4.2 1.6; 10.8). Collectively, these results indicate that the addition of supervised exercise during obesity pharmacotherapy improves maintenance of healthy body weight and body composition after treatment termination. More participants who had previously received combination treatment maintained a weight loss of at least 10% of initial body weight one year after treatment termination compared with participants who had received liraglutide alone or placebo.