The lack of overlap between the two stripes indicates a significant difference in efficacy between the two drugs. Distribution of typical pure effect values for weight reduction at week 52 for each drug Based on the final model parameters, we simulated the time-course distribution of weight reduction for each GLP-1RA drug. This study established time-course, dose-response, and covariate models for each drug. Thus, dropout rates can reflect the safety and efficacy of medications to some extent. These findings provide a reference for developing inclusion and exclusion criteria for future clinical trials on GLP-1RA drugs. The participants included in this study had an average baseline weight of 72.2–121 kg and an average baseline BMI of 24.1–45.1 kg/m2, with the male proportion ranging from 19.1 % to 100 %. However, the current dose of injectable Semaglutide (2.4 mg) is close to its efficacy plateau and further dose increases are unlikely to significantly improve its effectiveness. The results suggested that for certain drugs, such as Tirzepatide, BI , Semaglutide, and Mazdutide, a 26-week course only achieved 46.4 % to 69.4 % of their maximum effect. She's also co-author of a new book about obesity with Oprah Winfrey, called "Enough." … Over time, somebody who responded to Wegovy really well at the beginning, five, 10, 20 years from now, probably will need some other more powerful or different acting medication.” “Not everybody responds to GLP-1,” she tells TODAY.com. “There's a huge pipeline of new medications that are coming,” Dr. Melanie Jay, director of the NYU Langone Comprehensive Program on Obesity Research, tells TODAY.com. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are cornerstone therapies for type 2 diabetes, obesity and cardiovascular health.The weight loss benefits of SGLT-2 inhibitors typically are less than those of GLP-1 agonists.This is difficult because weight loss activates central and peripheral compensatory mechanisms that counter weight loss and favor weight gain.4 When lifestyle intervention is the sole treatment, weight is typically regained even with continued compliance.6 Treatment requires a comprehensive approach that includes lifestyle interventions, pharmacotherapy and in some instances, bariatric surgery.WHO supports country efforts to improve the availability of medicines, including GLP-1 therapies.This study compared the efficacy and safety profiles of different GLP-1 receptor agonists (GLP-1RAs) for weight reduction and explored the related influencing factors, providing quantitative information for the development of GLP-1RAs and their clinical use.If you miss a dose of Ozempic®, use it as soon as possible within 5 days after your missed dose.As most of the included studies only reported dropout rates and the incidence of adverse events at the endpoint, we were unable to establish a time-course model for them. Parks and Rosebrough first expressed concerns regarding human safety with liraglutide as early rodent trials demonstrated an increased risk of medullary thyroid carcinoma . A somewhat paradoxical effect has been demonstrated with GLP-1 usage and other agents for type 2 diabetes in which rapid improvement in glycemia results in worsening of retinopathy . Tirzepatide has demonstrated total lean mass loss as well, although additional studies are needed to determine the impact of this 134,182. 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 . And while the global rise in obesity rates has underscored the need for more effective and accessible treatment options, traditional approaches to weight loss like proper nutrition and exercise have often been limited by modest outcomes. In this review, we explore the current medical therapies for obesity, including all major categories, individual mechanisms of action, pharmacokinetics and pharmacodynamics, adverse effects, risks, and absolute contraindications. This review investigates the various pharmacologic treatments for overweight and obesity in adults, especially glucagon-like peptide 1 (GLP-1) agonists. Tirzepatide injection is also used to help lose weight and keep the weight off in patients with obesity caused by certain conditions. We focused primarily on clinical trials conducted in humans and also included in vitro and animal studies for mechanistic and molecular insights. We limited our search to studies from January 1995 onwards, with further relevant studies identified from citations within papers. This model of body fat regulation was widely adopted in the 1990s with the discovery of leptin 3,4. It is thus not surprising that these same side effects of rapid weight loss are seen as a class effect. Furthermore, patients with type 2 diabetes are inherently at higher risk of pancreatitis . Tirzepatide can uniquely induce weight loss beyond what is achieved with selective GLP-1 agonists alone. Woman Loses 130 Pounds and Finally Buys 1 Item of Clothing for the First Time Time-course, dose-response, and covariate models were used to describe the efficacy characteristics and influencing factors of different GLP-1RAs. The FDA has approved glucagon-like peptide-1 (GLP-1) receptor agonists such as Liraglutide, Semaglutide, and the GLP-1/gastric inhibitory polypeptide (GIP) dual agonist Tirzepatide for the treatment of obesity. Maintaining a healthy diet and regular physical activity are important components of any obesity chronic care programme. GLP-1 therapies (glucagon-like peptide-1 receptor agonists) are a class of medications that mimic the natural GLP-1 hormone, which helps regulate blood sugar and appetite. Metsera, a company that was recently bought by Pfizer, is also investigating monthly GLP-1 and amylin analog drugs. Lower blood sugar helps control type 2 diabetes. Tirzepatide (Mounjaro) is a similar kind of medicine called a dual-acting GLP-1/GIP agonist. The brand name of that medicine is Rybelsus. If you have type 2 diabetes and you want to find out if these medicines might be useful for you to lose weight, talk with your diabetes care team.However such risk in humans is still under investigation.However, elderly patients are more sensitive to the effects of this medicine than younger adults.Regular physical activity is also recommended as a component of weight loss programs not only for energy expenditure, but for cardiometabolic health as well .If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.Other GLP-1 agonists appear to be somewhat less effective for weight loss.She's also co-author of a new book about obesity with Oprah Winfrey, called "Enough."It helped one-third of the non-diabetic study patients achieve a loss of 10% of their body weight and also helped them sustain their weight loss for upwards of 1 year .At 3 years of follow-up, tirzepatide use led to a sustained mean loss of weight of 20% with less likelihood of deterioration to diabetes in persons with obesity and prediabetes when compared to placebo . SELECT also showed better cardiovascular outcomes in persons with obesity and without diabetes who had previously undergone coronary artery bypass graft surgery . The benefit of the GLP-1 agonists may be from the reduction of adiposity, or non-adiposity related. Reductions in food intake and body weight have been found, implying that both the hypothalamus and brainstem are important in the control of energy intake and body weight 119,120. There are conflicting data in animal models regarding GLP-1-related drugs stimulating energy expenditure . The additional properties of inhibition of glucagon secretion and inhibition of caloric intake accelerated the development of GLP-1 receptor agonists for usage in type 2 diabetes management . 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 .Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.However, even during active weight loss, metabolic adaptation seems to be set into motion, and in fact may be triggered by achieving 11% of total body weight loss 236,237.But both experts say not everyone needs to lose that much weight.Not only that, adipose tissue accumulates when a person is overweight or obese and functions as an organ.Studies suggest that GLP-1 drugs are not a direct cause of depressive symptoms in weight loss .Even more recently in 2022, a symposium was convened to discuss the state of the science of weight loss maintenance, known as the Pennington Biomedical Scientific Symposium .Patients are advised to consume a low-fat diet to combat the side effects of oily stool . For those with untreated obesity and seeking active weight loss, decreasing hunger and achieving caloric restriction is seemingly the primary process that needs to occur. The conceptual framework for weight regain and weight loss maintenance is based on the theory that the human body acts to defend a particular body mass, via the hypothetical “settling point” of weight 226,227,228. This can be attributed to the persistent effects of metabolic adaptation, the phenomena seen in weight regulation that may cause weight regain and potentially a weight loss plateau . In addition to its effect on body weight, a variety of health benefits have been ascribed to it. Regular physical activity is also recommended as a component of weight loss programs not only for energy expenditure, but for cardiometabolic health as well . In a randomized study of overweight adults, following a low-fat or high-fat diet with average or high protein resulted in an average 7% weight loss at 6 months, irrespective of diet type . Exceeding 6-12 months of use may have undesired effects by increasing LDL cholesterol and cardiovascular risk in some studies, but others have found no difference 50,51,52,53. Semaglutide (subcutaneous route) It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. This medicine may increase your heart rate while you are at rest. This medicine may cause severe stomach or bowel problems. Reported onset times ranged from 6.4 weeks (Orforglipron) to 19.5 weeks (Tirzepatide). Fifty-five studies involving 16,269 participants and 12 GLP-1RAs were included. Subgroup analyses were performed to explore efficacy differences in receptor specificity. WHO supports country efforts to improve the availability of medicines, including GLP-1 therapies. According to the 2021 Behavioral Risk Factor Surveillance Survey, the rates in Missouri adults are even higher with prevalence of 37.2% being obese and 32% being overweight.3 Finally, as the study included only English-language publications, there may have been a publication bias. 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. Ensuring quality requires regulated distribution and prescription by a qualified health care providers, strong oversight, patient education, and global cooperation to protect public health. About GLP-1 therapies for obesityWHO defines obesity as having a Body Mass Index (BMI) of 30 or higher in adults. This guideline is a key deliverable under the WHO acceleration plan to stop obesity and will be updated regularly as new evidence emerges. 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. Once patients decide to start medication, they should be counseled on side effects and how to take the medication. These medications are subcutaneous injections that patients do on their own. For long-term weight loss maintenance there would need to be an increase in weekly exercise to three hundred minutes, which is typically not sustainable.4 Additionally, individual or group sessions in a weight management program should be considered. Over 56% of participants achieved mean weight loss of 7.5% with liraglutide versus 4% with placebo. GLP-1 agonists mimic the way a hormone called glucagon-like peptide 1 works in the body. It's also used to control blood sugar and can support weight loss. GLP-1 agonists include the following medicines. GLP-1 agonists for type 2 diabetes are generally taken by a shot, also called an injection. “Labels can be very misleading, making a person think it’s healthier than it is,” Snashall said. First, individual estimates of model parameters for each drug group and their standard errors were obtained using data output by the NONMEM software. The potential covariates examined included age, male ratio, baseline weight, and baseline BMI. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool 2.0 . In cases where studies reported both intention-to-treat (ITT) and per-protocol (PP) results, the ITT analysis results were prioritized for inclusion for conservatism. Search terms included “obesity” and “GLP-1,” and the search was limited to clinical trials published in English. 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. We also discuss total cost and cost-effectiveness compared to other categories, long-term adherence, barriers to use, and reasons for discontinuation of this drug category. A Multi-Pronged Approach to Avoiding Weight Regain Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of semaglutide injection in the elderly. In this setting, prevention of weight regain may be better-termed weight loss maintenance. It is worthwhile to point out that a weight loss plateau is often stated with the assumption that additional weight loss is desired, but difficult to achieve. The general trajectory of weight loss with initiation of GLP-1 therapy has been well-studied (Table 2) 218,219,220. Common adverse effects of GLP-1 agonists and approaches to minimizing these consequences. As with all new medications or those whose use increases due to expanded indication, ongoing monitoring and close surveillance by both patients and clinicians continue to be necessary. This study provides a quantitative evaluation of the efficacy and safety of GLP-1RAs and offers valuable insights into the assessment of new drugs for weight reduction. Researchers from Oxford University analyzed 37 studies that examined what happened when people stopped taking weight loss drugs. Recent studies have shown that patients on high-dose semaglutide can lose an average of 15% to 20% of their body weight, a level previously achievable only with bariatric surgery. Other GLP-1 agonists appear to be somewhat less effective for weight loss. All GLP-1 agonists can help with weight loss. Other companies are targeting GLP-1 users but not mentioning the drugs on their labels or menus. She said the products have broad appeal; 77% of Vital Pursuit sales are coming from households where no one is using GLP-1 drugs. Big food companies expect the demand for GLP-1 drugs only to grow as the injected medication becomes available in pill form, which happened with Wegovy last week. However, GLP-1 drugs carry known risks and, since their use for weight loss is recent, may carry unforeseen risks as well. GLP-1 medications have revolutionized weight loss and can reduce body weight in obese patients by between 15% and 25% on average after about 1 year. One study in the journal Addiction found that people addicted to alcohol who also had a prescription for Ozempic or similar drugs had a 50% lower rate of binging alcohol, compared to those who were not on the medications. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. For instance, the SELECT trial demonstrated the cardiovascular benefit of the GLP-1 receptor agonist semaglutide beyond that of weight loss . Therefore, most of the effect of weight loss via GLP-1-related pathways may be related to a decrease in energy intake, rather than the direct effects on energy expenditure . The metabolic efficacy of bariatric surgery in increasing gut production of GLP-1 to supraphysiologic levels postprandially is considered a major factor in early weight loss . If you use this medicine with insulin, do not mix them into the same syringe. Keep track of where you give each shot to make sure you rotate body areas. Use a different body area each time you give yourself a shot. This medicine is given as a shot under the skin of your stomach, thighs, or upper arm. Be sure you understand exactly how the medicine is to be injected. Such a rapid increase in usage led to multiple drug shortages beginning in 2022 which continued through late 2024 . There are a number of proposed mechanisms including reduction of inflammation, improvement of endothelial and ventricular function, as well as decreasing platelet aggregation . In this placebo-controlled trial, subjects were over the age of 45 years, had a BMI of 27 or above, and established cardiovascular disease. GLP-1 secretion seems to be impaired in obese subjects, which informs at least the partial role of GLP-1 in the pathophysiology of obesity 94,95,96. This drug from Novo Nordisk also mimics both GLP-1 and amylin, and is being tested as a daily pill and a weekly injection. The once-weekly injection from Novo Nordisk combines cagrilintide, an amylin analog, with semaglutide — the active ingredient in Ozempic and Wegovy. Both of them work at the level of the pancreas and at the level of the brain and other organs in the body,” adds Jay, who has also done consulting work for Novo Nordisk. "Instead, our findings suggest the prominent FDA warning has created heightened vigilance, leading to more-frequent thyroid examinations for those starting these drugs." This front-loaded risk profile is inconsistent with the known biology of carcinogenesis, which typically requires a longer latency period, suggesting an alternative explanation to the drug causing new cancers. Furthermore, the absolute risk was low, with a thyroid cancer diagnosis occurring in only 0.17% of the 41,112 patients who initiated GLP-1RA therapy. Many people who take these medicines also see their blood pressure improve. An example would include the usage of liraglutide that helped one achieve a particular amount of weight, but continued usage of the drug led to weight regain, would switching to Contrave help to achieve weight loss maintenance?The recent advances in obesity medicine have led to many changes in the approach to patients with obesity and there is hope that this can be a manageable disease thus mitigating the consequences of it.This model of body fat regulation was widely adopted in the 1990s with the discovery of leptin 3,4.There are conflicting data in animal models regarding GLP-1-related drugs stimulating energy expenditure .This medicine is given as a shot under the skin of your stomach, thighs, or upper arm.The results indicated that at 52 weeks, the weight reduction effects of mono-agonists, dual-agonists, and triple-agonists were 7.03 kg, 11.07 kg, and 24.15 kg, respectively.For instance, Orforglipron demonstrated the fastest onset (6.4 weeks); conversely, Tirzepatide had the slowest onset (19.5 weeks), taking 46 weeks to reach its efficacy plateau.“This isn’t a failing of the medicines—it reflects the nature of obesity as a chronic, relapsing condition.The shaded gray area represents the range of treatment duration in the included studies, while the orange points indicate the effect values at 26 weeks and 52 weeks. Randomized double-blinded placebo-controlled withdrawal studies were performed in both semaglutide and tirzepatide with crossover to placebo at 20 weeks and 36 weeks, respectively 242,243. Cessation of these drugs to see if weight maintenance could be achieved was largely unsuccessful (Table 3). However, even during active weight loss, metabolic adaptation seems to be set into motion, and in fact may be triggered by achieving 11% of total body weight loss 236,237. It is meaningful to note that GLP-1 agonists have been increasingly examined outside the effects on type 2 diabetes and obesity. Qsymia has the longest-term data of the available oral anti-obesity drugs, upwards of 108 weeks . For Contrave, a weight loss plateau seems to occur for all the COR studies around 32 to 36 weeks with overall weight loss around 8 to 9%. Most side effects are gastrointestinal and include nausea, vomiting, diarrhea, and constipation. If there are significant side effects a slower titration may be helpful but is usually limited by insurance. The cost can be prohibitive, most insurances require prior authorization and making patients aware of this up front helps reduce frustration and phone calls/messages. Liraglutide is daily, while semaglutide and tirzepatide are weekly. To date, there are two GLP-1s approved for weight loss; liraglutide (Saxenda) and semaglutide (Wegovy), and one GLP-1 and gastric inhibitory polypeptide also know as glucose-dependent insulinotropic polypeptide receptor agonist (GIP), tirzepatide (Zepbound). Up until recently, the medications used to treat obesity were not very effective and had many limiting side effects and contraindications. Many of the effects of obesity can be halted, reversed, and prevented by losing weight. Low blood sugar is a more serious risk linked to GLP-1 agonists. More common side effects often improve after taking the medicine for a while. When blood sugar starts to rise after a person eats, these medicines cause the body to make more insulin. Sign up for free and stay up to date on research advancements, health tips, current health topics, and expertise on managing health. SGLT-2 inhibitors aren't recommended for people who have had diabetic ketoacidosis. Rarely, SGLT-2 may be linked to a higher risk of infection in the feet and lower legs. Studies have linked GLP-1 agonists with certain thyroid tumors in rats. Qsymia has demonstrated overall efficacy for weight loss maintenance, achieving sustained weight loss of 9-10% at the 108-week mark compared to 1.8% for placebo . However, the weight regain is relatively mild and by 104 weeks there is still overall weight loss. Pharmacological treatments for weight loss have expanded and, while GLP-1 agonists are the focus of this review, other choices are available and summarized here. Finally, the microbiome has a variety of mechanisms through which it affects obesity, and pre/probiotic therapies could be a helpful addition to a weight loss regimen 58,59. Average baseline weight ranged from 72.2 to 121 kg, with a median weight of 95.8 kg; average baseline Body Mass Index (BMI) ranged from 24.1 to 45.1 kg/m2, with a median of 33.9 kg/m2. The selected 55 studies included a total of 16,269 participants, with an average age range from 29.5 to 64.7 years, and a median age of 53.6 years. When heterogeneity was obvious (I2 ≥ 50 %), a random-effects model was used to summarize the RRs; otherwise, a fixed-effect model was applied. Heterogeneity among studies was assessed using the I2 statistic, with an I2 value of 50 % or higher indicating obvious heterogeneity. As most of the included studies only reported dropout rates and the incidence of adverse events at the endpoint, we were unable to establish a time-course model for them. Points connected by a line originate from the same study arm, while points sharing the same color belong to the same study. Observed efficacy data are represented by points, with symbol size reflecting sample size. The VPC plots (Fig. 2) showed that most observed efficacy values fell within the 95 % CI of the model predictions, indicating that the model had a good predictive capability. Orforglipron had the fastest onset at 6.4 weeks, whereas Tirzepatide had the slowest at 19.5 weeks (Supplementary Fig. S3). Treatment duration varied from 6 weeks to 104 weeks, with a median duration of 26 weeks. Additionally, there are those who are attempting to prevent weight regain after already achieving a weight-reduced state. Definitions of weight regain may vary, namely the duration and how much is considered significant. Though more evidence is needed such guidance is useful to patients and clinicians at the present time 216,217. A recent multi-society joint guidance statement advocated for an individualized approach based upon each patient’s unique factors rather than a one-size approach of holding this medication for all patients undergoing procedures . The Smoothie King chain has a “GLP-1 Support Menu,” while several meal kit brands cater to patients, like Factor’s “GLP-1 Balance.” Sales have been brisk and the company is adding new meals to the lineup, Barnes said. Drugs like Ozempic and Wegovy mimic the naturally occurring hormone GLP-1, which the body produces in the small intestine to control blood sugar levels, digestion and appetite. "There is an exponential increase in the use of GLP-1 receptor agonists because of their potent impacts on management of diabetes, heart disease and reduction in body weight," explains Nayantara Coelho-Prabhu, M.B.B.S., a gastroenterologist and researcher at Mayo Clinic in Rochester, Minnesota, who served as the publication's corresponding author. Meals marketed for GLP-1 users also are attracting non-users, including people who have come off the drugs but want to maintain weight loss. Studies report that the discontinuation rate due to adverse effects were lower with semaglutide than liraglutide ( 3.2% vs 12.6% respectively).6 Despite these side effects, trials showed that nausea and vomiting did not really contribute to patients’ weight loss, it was the lower energy intake that has been thought to be responsible for the weight loss. Despite this there is still some hesitancy in using medication for weight loss which comes from a variety of reasons including, but not limited to, lack of recognition of obesity as a disease, lack of provider experience, biases, concerns about safety and efficacy, cost, and lack of reimbursement. 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. If you will be using semaglutide at home, your doctor will teach you how the injections will be given. This medicine comes with a Medication Guide and patient instructions. When you start using this medicine, it is very important that you check your blood sugar often, especially before and after meals and at bedtime. The presence of other medical problems may affect the use of this medicine. However, the only truly long-term strategy that has been the most successful for long-term weight loss is surgical weight loss. Ideally, the chosen initial intervention for weight loss would also be effective for weight loss maintenance. What remains to be seen is if the mixing and matching of the initial weight loss strategy, whatever this may be, with another weight loss maintenance strategy will lead to successful weight maintenance. In this article we review the glucagon like peptide −1 receptor agonist (GLP-1) medications and discuss how to approach using them for weight loss and management in non-diabetic patients. Third, this study's comparison of the efficacy and safety of various GLP-1RA was not based on direct head-to-head trials, and some GLP-1RA drugs are still under development. This study found that the dropout rates for injectable Semaglutide, Liraglutide, Mazdutide, Retatrutide and Tirzepatide were significantly lower than those for the placebo, suggesting that these drugs have a favorable risk-benefit ratio. Participants experiencing adverse reactions or poor effectiveness during the use of weight reduction medications may opt to discontinue the drug. Thus, apart from modifying the specificity of drugs to receptors, enhancing their affinity can significantly improve the weight reduction outcomes of GLP-1RA drugs. The labels aren't backed by standards and may confuse some customers by making them think that eating frozen and ready-made meals that mention the medications will give them the benefits of the drugs. Badaracco said it’s easy for GLP-1 users to get dehydrated since the drugs may block the body's thirst signals. Christen said she generally recommends that patients eat grams of protein per meal, or 1.2 grams per kilogram of body weight daily. Dieticians say people taking GLP-1 drugs need to read ingredient lists and talk to experts about what nutrients they need – and don’t need. Notably, vital signs should be reviewed as there may need to be adjustments of other medications as the benefits of weight loss come through, especially blood pressure medications. 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 . Keywords were then refined based on the relevance of the results, and additional terms were searched to survey related areas including “cardiometabolic risk factors”, ‘sarcopenia”, “exercise”, “body mass index (BMI)”, and “appetite”. Having patients track intake and physical activity has been shown to be helpful. Working with a dietician may help patients alter their food choices, but discussion of decreasing caloric intake is also helpful. Part of the GLP-1 action is to activate metabolism of brown fat and adipose redistribution with decreased visceral fat and relative increase in lower-body subcutaneous fat deposition.8 GIP is also an incretin hormone involved in energy and nutrient metabolism through cell surface receptor signaling in the brain and adipose tissue.2 Some studies suggest the delayed gastric emptying is only in the first hour and overall gastric emptying did not seem to be affected.7,8 GLP-1 is also expressed in the brainstem, endocrine pancreas, and immune system. This medicine is also used to lower the risk of heart attack, stroke, or death in patients with type 2 diabetes, obesity, and heart or blood vessel disease. "Our study found that patients using GLP-1 receptor agonists are more likely to have inadequate bowel preparation during colonoscopy, even when we account for other comorbidities, such as diabetes, heart failure, inflammatory bowel disease, constipation and use of opioid medications." "Our study found that patients using GLP-1 receptor agonists are more likely to have inadequate bowel preparation during colonoscopy, even when we account for other comorbidities, such as diabetes, heart failure, inflammatory bowel disease, constipation and use of opioid medications," explains Dr. Coelho-Prabhu. Finally, parameters from the distribution of pharmacodynamic parameters in each subgroup were randomly selected, and drug effects at different time points were calculated.An analysis was conducted on the total dropout rates for the 12 types of GLP-1RA drugs.A significant disadvantage of using these medications is the high rate of weight regain when they are discontinued.Psychological well-being is an important aspect of both eating behaviors and weight loss 264,265.Other companies are targeting GLP-1 users but not mentioning the drugs on their labels or menus.Some studies suggest the delayed gastric emptying is only in the first hour and overall gastric emptying did not seem to be affected.7,8 GLP-1 is also expressed in the brainstem, endocrine pancreas, and immune system.For example, with Liraglutide, participants aged 30 years reduced their weight by 10.1 kg over 52 weeks, whereas those aged 60 years showed a reduction of 3.31 kg.But the risk of low blood sugar typically only goes up when a person also is taking another medicine that's known to lower blood sugar. The researchers collected data on relevant patient comorbidities, type of bowel preparation, concurrent medications, quality of bowel preparation and findings on colonoscopy. "These medications are known to delay gastrointestinal motility, which can adversely affect bowel preparation quality for colonoscopy," says Dr. Coelho-Prabhu. The results of the study were published in Gastrointestinal Endoscopy in 2025 and shared in a poster presented at Digestive Disease Week 2025. These findings should allow clinicians to prescribe these valuable medications with greater confidence. The graph on the left represents the 95 % CIs of the typical pure effect of weight reduction over 52 weeks, with the yellow stripe indicating Liraglutide and the purple stripe representing other drugs. However, quantitative comparisons of the efficacy of these GLP-1 receptor agonist drugs in obesity treatment, particularly between mono-, dual-, and triple-agonists, are still lacking. At 52 weeks, weight reduction effects were 7.03 kg, 11.07 kg, and 24.15 kg for mono-agonists, dual-agonists, and tri-agonists, respectively. GLP-1 Receptor Agonists and Weight Loss This medicine may cause serious allergic reactions, including anaphylaxis and angioedema, which can be life-threatening and require immediate medical attention. This medicine does not cause hypoglycemia (low blood sugar). Pancreatitis (swelling of the pancreas) may occur while you are using this medicine. In case of emergency—There may be a time when you need emergency help for a problem caused by your diabetes. Do not use this medicine for at least 2 months before you plan to become pregnant. Publication types "A lot of people are going to like that," Levy says. People trying to lose weight may opt for long-acting monthly shots instead of weekly injections in the future. “At least 25% of the patients I see don't want anything to do with needles,” she notes. The pill versions are especially good for “needle phobic” people, Levy says. “For somebody who has a lower BMI of 30, this might be overpowering,” Levy noted. Other side effects not listed may also occur in some patients. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Along with its needed effects, a medicine may cause some unwanted effects. Regarding vomiting, except for Liraglutide, which was lower than the placebo, the incidence rates for other GLP-1RA drugs were similar to or higher than those for the placebo. An analysis was conducted on the total dropout rates for the 12 types of GLP-1RA drugs. The figure on the right illustrates the model-predicted typical values of weight reduction for Liraglutide (A) and Semaglutide (B) at various age levels. The box plot on the left displays the observed weight reduction values for Liraglutide (A) and Semaglutide (B) across different age groups. However, the prevalence of obesity along with the need for more effective anti-obesity treatments prompted the study of the first daily GLP-1 receptor agonist, liraglutide. A number of clinical trials in persons with diabetes have been subsequently performed and frequently cited for the clinical efficacy of exendin-4 147,148. The usage of compounding pharmacies does come with risks as the medications produced are not FDA-regulated . In an analysis of one US health systems database a 700% increase in GLP-1 prescribing over the past four years was noted, primarily driven by prescriptions for obesity . Similarly, the subcutaneously once weekly formulation of the GLP-1 receptor agonist semaglutide showed equally promising results for weight maintenance . Obesity-driven inflammatory processes are responsible for a large portion of the damage inflicted by excess weight (Figure 1). Obesity is a non-communicable pandemic that continues to expand and affect over 1 billion people globally 11,12,13,14. Kim et al. found a linear association between waist circumference and all-cause mortality in a study on 23,263,878 subjects over the age of 20 years . A BMI (in kg/m2) in the range of 18.5–24.9 is considered normal, 25–29.9 is overweight, and ≥30 is considered obese. Obesity is traditionally defined as an excess of body fat, and is classically categorized in clinical practice in terms of body mass index (BMI). Achieving success with pharmacologic treatment and then weaning to avoid future negative effects would be ideal. They carry a boxed warning for people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Treatments such as bariatric surgery create hesitancy among patients due to their invasiveness. Appropriate studies have not been performed on the relationship of age to the effects of Ozempic® in the pediatric population. In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. Semaglutide injection is also used together with diet and exercise to help lose weight and keep the weight off in patients with at least one weight-related medical condition. Quality of bowel preparation for colonoscopy in patients on glucagon-like peptide-1 receptor agonists. If you miss a dose for more than 4 days, skip the missed dose and go back to your regular dosing schedule. If you miss a dose, use it as soon as possible within 4 days after your missed dose. This medicine is given as a shot under the skin of your stomach, thighs, or back of the upper arm. Tirzepatide injection is used to treat type 2 diabetes. "Future studies should examine the optimal interval prior to colonoscopy when these medications should be held," says Dr. Coelho-Prabhu. The rapidly rising use of glucagon-like peptide-1 (GLP-1) receptor agonists has caused gastroenterologists to question whether these medications can affect bowel preparation. Given that the increased risk appears to be an artifact of detection bias, these findings do not support implementing routine thyroid cancer screening for patients initiating GLP-1RA therapy. By 12 months, an estimated 2.1% of GLP-1RA users had received an ultrasound, compared with only 1.5% of users of other diabetes medications. The retrospective study included 3,344 patients using GLP-1 receptor agonists and 2,891 age- and sex-matched controls, all of whom underwent colonoscopy in 22 endoscopy units across 18 sites at Mayo Clinic sites in Minnesota, Wisconsin, Florida and Arizona. To explore this issue, Mayo Clinic researchers reviewed the electronic health records of more than 6,000 adult patients undergoing colonoscopy, and they compared the quality of bowel preparation between a group of patients using GLP-1 receptor agonists and a control group. For most patients without a personal or family history of MTC or MEN2, the proven metabolic and cardiovascular benefits of GLP-1RAs appear to far outweigh what this study suggests is a surveillance-driven risk of diagnosis. 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. Our new guidance recognizes that obesity is a chronic disease that can be treated with comprehensive and lifelong care,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “Obesity is a major global health challenge that WHO is committed to addressing by supporting countries and people worldwide to control it, effectively and equitably. In September 2025, WHO added GLP-1 therapies to its Essential Medicines List for managing type 2 diabetes in high-risk groups. Meals and snacks with “GLP-1 Friendly” labels on the packaging are becoming more common in U.S. supermarkets as a growing number of Americans try obesity drugs like Wegovy and Zepbound to lose weight. With just 5% weight loss, there is noticeable improvement in health and reduced risk of complications. The recent advances in obesity medicine have led to many changes in the approach to patients with obesity and there is hope that this can be a manageable disease thus mitigating the consequences of it. Present and Future of Weight Loss While largely successful as an anti-diabetic drug therapy, the effects on both reducing food intake and promoting weight loss in persons with diabetes and animal models prompted further study as an anti-obesity medication 87,88. Researchers concluded that those taking tirzepatide were “significantly more likely to achieve weight loss,” but added that more studies are needed to better understand the full range of benefits and effects both drugs have on patients. GLP-1 receptor agonists are a class of medicines that help lower blood sugar, support weight loss, reduce the risk of heart and kidney complications, and can even lower the risk of early death in people with type 2 diabetes. Participants also had improvement in waist circumference, systolic and diastolic blood pressure, fasting insulin level, lipid levels, and A1c with most of the participants who had prediabetes achieving normoglycemia.2 This demonstrates a significantly decreased 10-year predicted atherosclerotic cardiovascular disease risk.13 Recently, semaglutide was approved for reducing risk of cardiovascular events in patients with cardiovascular disease who are obese or overweight. Tirzepatide was studied in the SURMOUNT-1 trial and was shown to have average weight loss of 15% with the 5mg dose, 19.5% with 10mg and 20.9% with the 15mg dose, whereas the placebo group had 3.1% weight loss.2 Similar to the STEP 1 trial, SURMOUNT-1 included individuals with BMI greater than or equal to 30 kg/m2 or greater than or equal 27 kg/m2 with one or more weight-related comorbidity, except diabetes, and patients were treated over 72 weeks. In general, studies have found that tirzepatide and semaglutide are the most effective for weight loss. But the amount of weight loss depends on the type of medicine and the dose. There are two main groups of type 2 diabetes medicines that lower blood sugar and also may lead to weight loss. 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. When switched to placebo there was invariably weight regain, implying that the loss of inhibition of hyperphagia drove this process. Beyond working with a doctor to ensure nutritional benchmarks are met, the recommendations include screening for a history of disordered eating and taking into account a person’s whole health before prescribing. Because GLP-1 medications completely rewire hunger and fullness cues, there’s a concern about getting proper nutrition while taking them. And beyond gastrointestinal effects, researchers are investigating concerns about long-term impact, such as gallbladder issues, pancreatitis and potential links to thyroid tumors. This medicine may cause dehydration which can lead to acute kidney injury. However, low blood sugar can occur when you use tirzepatide with other medicines, including insulin or sulfonylureas, that can lower blood sugar. This medicine may cause severe stomach and bowel problems. The follow-up STEP-5 trial demonstrated that semaglutide could sustain weight loss over 104 weeks or nearly 2 years . The STEP-1 trial is considered the pivotal trial that demonstrated 14.9% weight loss at 68 weeks with semaglutide 2.4 mg . A 3-year extension of the SCALE trial showed that persons with overweight or obese and prediabetes taking liraglutide had a reduced risk for developing type 2 diabetes with greater weight loss compared to those taking a placebo The Satiety and Clinical Adiposity Liraglutide Evidence (SCALE) trial demonstrated one-third of patients lost 10% of their body weight in 1 year with sustained weight loss demonstrated at 2 years 149,150. The amount of medicine that you take depends on the strength of the medicine. If your dose is different, do not change it unless your doctor tells you to do so. Use this medicine on the same day each week, at any time of the day, with or without meals. Never share medicine pens with others under any circumstances. It is acceptable to inject these in the same body area, but the shots should not be right next to each other. More data are required to determine whether the weight reduction effects of tri-agonists generally surpass those of dual- and mono-agonists. This study systematically quantitatively assessed the efficacy and safety characteristics of 12 marketed and experimental GLP-1RA drugs. Taking injectable Semaglutide (1.0 mg) as an example, the weight reduction effects at 52 weeks for subjects aged 45, 55, and 60 were 9.88 kg, 7.27 kg, and 6.24 kg, respectively, with the latter being 3.64 kg lower than the former (Fig. 6). If you have type 2 diabetes and you want to find out if these medicines might be useful for you to lose weight, talk with your diabetes care team. But it's not clear whether these benefits are from the medicine or a result of weight loss. The weight loss benefits of SGLT-2 inhibitors typically are less than those of GLP-1 agonists. As with any medicine, there is a risk of side effects when taking a GLP-1 agonist. But it's not clear exactly how GLP-1 agonists lead to weight loss. Its ability to promote weight loss can also alleviate obesity-related stress on the kidneys, improving overall kidney function. It’s thought to be more effective than semaglutide in helping people lose weight, according to research published in JAMA Internal Medicine in July 2024. While the benefits are undeniable, the blockbuster growth and use of GLP-1 drugs has also highlighted potential side effects. However, if one were to choose a mechanism to prevent weight regain, targeting hunger would seem to be the better alternative due to the greater effect of metabolic adaptation on hunger, rather than the decrease in energy expenditure . The drivers for weight regain are hypometabolism and hyperphagia in the weight-reduced state 229,230,231. Ultimately, understanding the existing forces that occur in a weight-reduced state may help to understand what may drive weight regain 224,225. Dual agonists for GLP-1/GIP or GLP-1/GCG receptors, and triple agonists for GLP-1/GIP/GCG receptors have been developed to enhance weight reduction and metabolic outcomes . Reducing weight by 5 % or more significantly improves obesity-related health complications . No, while GLP-1 therapies are used for the treatment of people with obesity, they should not replace other means of weight control. Clinical takeaways: Reassurance and a reframed perspective Previous studies have shown that the efficacy of weight reduction medications is influenced by baseline weight, with individuals having higher baseline BMI experiencing larger reductions in weight . The results indicate significant variability in the efficacy of these drugs in reducing body weight. The results indicated that at 52 weeks, the weight reduction effects of mono-agonists, dual-agonists, and triple-agonists were 7.03 kg, 11.07 kg, and 24.15 kg, respectively. Covariate analysis identified age as a significant factor affecting the weight reduction efficacy of GLP-1RA drugs. For example, with injectable Semaglutide, at doses of 0.05 mg, 1.0 mg, and 2.4 mg, the weight reduction effects at 52 weeks were1.21 kg, 7.6 kg, and 9.05 kg, respectively (Fig. 4). GLP-1 medications can cause a range of side effects related to the gastrointestinal system as well as changes in muscle mass and effects on the appearance of the face and loss of hair (Figure 2). The SURMOUNT-1 trial demonstrated a 15 mg dosage of tirzepatide in non-diabetic obese subjects leads to 20.9% weight loss at week 72 with sustained weight loss during a 3-year extension period 134,137. Liraglutide was the first injectable daily GLP-1 receptor agonist that was approved by the FDA for weight loss in 2014. Ever since the UK Prospective Diabetes Study demonstrated modifiable retinopathy with improvements in glycemic control, clinicians and patients have aimed to improve glucose as a standard of management in type 2 diabetes . Studies to clarify this issue would particularly be needed for patients who are afflicted with sarcopenic obesity, a condition of a mismatch between muscle and fat mass. Rapid weight loss can also lead to what is known as an “Ozempic face”, where the cheeks become hollowed out, and wrinkles, as well as eye bags, become more pronounced. The most often reported side effects are nausea and vomiting which are a result of activation of specific GLP-1 receptors in the hindbrain and these symptoms can be mitigated with gradual dose escalation 155,156,157. The duration of the clinical trials included in this study ranged from 6 to 104 weeks, with a median treatment duration of 26 weeks. For instance, Orforglipron demonstrated the fastest onset (6.4 weeks); conversely, Tirzepatide had the slowest onset (19.5 weeks), taking 46 weeks to reach its efficacy plateau. In comparison, although the GLP-1/GIP and GLP-1/GCG dual-agonists also showed a trend toward increased efficacy, their improvement was not as pronounced as that of the tri-agonists. As a GLP-1/GIP/GCG tri-agonist, Retatrutide's interaction among the three receptors significantly enhanced its weight reduction effect. In terms of constipation, except for Danuglipron, which was lower than the placebo, the incidence rates for other GLP-1RA drugs were similar to or higher than those for the placebo. Since the FDA approval of liraglutide for weight loss in 2015, the use of this class of medication has exploded, particularly over the last few years with the availability of weekly GLP-1s including tirzepatide and semaglutide. At 3 years of follow-up, tirzepatide use led to a sustained mean loss of weight of 20% with less likelihood of deterioration to diabetes in persons with obesity and prediabetes when compared to placebo . An even greater weight loss is seen with this novel dual agonist, achieving upwards of a 22.5% weight loss at 72 weeks 134,135,136. 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. The green diamond points represent the efficacy values that reach the efficacy plateau (80 % of maximum effect). Values exceeding 80 % suggest that the treatment duration has approached or reached its efficacy plateau. Most of the observed efficacy data fall within the 90 % confidence interval predicted by the model, indicating that the model has good predictive ability. The green lines indicate the model-predicted 5th, 50th, and 95th percentiles of efficacy. The shaded gray area represents the range of treatment duration in the included studies, while the orange points indicate the effect values at 26 weeks and 52 weeks. The orange line represents the typical time-course curve of the drug, while the purple line represents the percentage of the efficacy at each time point relative to the maximum effect of each drug. Taking injectable Semaglutide (1.0 mg) as an example, the efficacy at 26 weeks, and 52 weeks was 5.77 kg, and 7.57 kg, respectively, representing 49.3 %, and 64.7 % of its maximum effect (Fig. 5). The results indicated that Liraglutide exhibited the fastest onset, reaching an efficacy plateau (80 % of the Emax value) by week 17, whereas Tirzepatide showed the slowest onset, requiring 46 weeks to reach the efficacy plateau. Values exceeding 80 % suggest that the dosage of the drug has approached or reached its efficacy plateau. There have also been ongoing shortages of some of the doses of the medications. It should be noted that the cost of future healthcare needed from consequences of obesity is likely to be more than that of the medication. Each of the three medications has coupons on the manufacturer website patients can apply for, however, if they have government insurance, they are exempt from qualifying. At this time, Medicaid and Medicare will not cover them for weight loss. Another form of semaglutide is available in a pill that's taken by mouth once a day. The first group is glucagon-like peptide 1 (GLP-1) agonists. MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. Clinical trial outcomes will determine whether these will be useful either on their own or in conjunction with GLP-1 agonists. Patients have also been reported to take “drug holidays” in which they pause the use of the drug intermittently for special occasions, but there is very little in the literature on this . “Semaglutide might also improve kidney health due to its direct effects on blood sugar control as well as weight,” Dr. John Whyte, chief medical officer at WebMD and a board-certified internist with expertise in drug development and medical policy, told Flow Space. These medicines are transforming obesity treatment and can achieve important weight loss. Research has found that about half of GLP-1 users stop taking the drugs within a year, so the question of whether the weight loss sticks is prudent. Researchers found that people who took semaglutide lost, on average, 3.6% of their body weight after three months; 5.8% after six months; and 8.3% after 12 months. The 12 GLP-1RA drugs were categorized based on receptor specificity into mono-agonists, dual-agonists, and triple-agonists. Impact of age on the weight reduction effects of Liraglutide (A) and Semaglutide (B) The shaded gray area represents the range of doses administered in the included studies, while the plotted points indicate the maximum, median, and minimum drug doses observed across the studies. The orange line represents the typical dose-response curve of the drug, while the purple line shows the percentage of efficacy at each dose relative to the maximum effect of each drug. Points on the right indicate the typical values of the pure effect of 52-week weight reduction for each drug, with error bars denoting 95 % CIs of the estimates. It is especially suitable for individuals with type 2 diabetes and/or insulin resistance . Treating obesity has evolved in recent years, with various shifts in dietary, pharmacological, and surgical strategies available for the management of obesity . Obesity also elevates the risk of developing some types of cancer including colorectal, esophageal, liver, and kidney malignancies 28,29,30,31,32. The inflammatory environment incites endothelial dysfunction further contributing to cardiovascular risk and hypertension 22,23,24. The lipid profile in obesity is marked by an increase in triglycerides and free fatty acids . Fiber is important for everyone, but it's particularly helpful for GLP-1 patients because constipation is a frequent side effect of the medications, she said. The difference is that GLP-1 users eat less because the drugs suppress their appetites, so the foods they do eat need to be packed with nutrients, Christen said. Some studies also suggest that GLP-1s may have a role to play in many other disease processes including Alzheimer’s, Parkinson’s, strokes, chronic pain, polycystic ovarian syndrome, and cancer.19 It also allows continued documentation of weight to demonstrate success with the weight loss efforts. In an ideal setting, weight loss achieved with GLP-1 agonist therapy in the short-term could be durable without pharmacotherapy for many years and perhaps over a lifetime. GLP-1 receptor agonist drug therapy is a key focus with consideration of the mechanism of action, clinical trials in weight management, and the potential role of the drug category in weight maintenance. The known risks of pancreatitis, gastroparesis, and lean body mass loss are variables to be considered as well. Fresh fruits and vegetables provide hydration, she said, and patients should also drink water throughout the day. Protein helps GLP-1 users maintain muscle mass as they lose weight. They can expect to eat around 50% less than they ate before they started taking the medications, she said.