Adverse effects are predominantly mild and transient, with nausea being the most commonly reported 10, 11. Extensive meta‐analyses have highlighted the efficacy and safety of GLP‐1RAs in achieving glycemic control, enhancing quality of life and significantly reducing major cardiovascular events in both diabetic and non‐diabetic individuals with obesity. In cases of severe renal impairment, certain GLP‐1RAs may require dosage adjustments or careful monitoring to avoid adverse effects such as accumulation or toxicity. Healthcare providers must carefully consider patient‐specific factors, such as underlying conditions and concurrent medication use, to ensure safe and effective treatment outcomes. Lorcaserin is as an appetite suppressant through activation of hypothalamic 5-HT2C receptors and was approved for use by the FDA in 2012.Patients included people of diverse ages, races and sexes.Owing to the delayed gastric emptying caused by liraglutide, the action of other drugs can be affected.Tirzepatide imitates both GLP-1 and GIP, increasing your body's production of insulin and lowering your blood glucose levels.A key point here is that targeting gut-brain signaling to induce satiety and blocking adaptive responses to weight loss constitute two distinct mechanisms of action.Resveratrol was considered the source of the “French paradox,” a phenomenon in which the French population, despite having a diet rich in fats, had a lower prevalence of obesity and cardiovascular diseases; this was attributed to red wine, which has a high content of this polyphenol .The effect of currently approved GLP-1 monotherapies for T2D on weight loss are presented in Table 2.They’re costly and may not be covered by health insurance. The dose should be administered for a minimum of 3 months before a further increase to the highest dose of 15/92 mg. According to the package insert, the dose of phentermine/topiramate should be gradually escalated. Although the actions of topiramate on the central nervous system have not been completely understood, rodent studies have suggested that it acts as a neurostabilizer and may boost thermogenesis 39,40. Liraglutide is a subcutaneous GLP-1 agonist, which is used daily for the management of diabetes mellitus type 2 and obesity/weight management . At the one-year point, excess weight loss as compared to placebo was 5.0 kg (95% CrI -5.94 to -3.96). The combination of phentermine-topiramate allows minimal side effects with proven efficacy for weight loss. In a study by Shi et al., phentermine-topiramate led to a mean difference (MD) of percentage body weight change of -7.97 (95%CI -9.28 to -6.66), while glucagon-like peptide 1 (GLP-1) agonists showed MD of -5.76 (95%CI -6.30 to -5,21) . The decision came after early studies involving people who are considered obese showed significant and lasting weight loss.This coverage began in 2011 when the Centers for Medicare & Medicaid Services implemented specific coding for IBT to encourage healthcare professional utilization.Among the patients who completed 4 years of treatment, the percentage of patients who achieved at least 5% weight loss was significantly higher in the orlistat group (52.8%) than in the placebo group (37.3%).It is licensed for use as monotherapy in those unable to take metformin or as add-on treatment.The Mayo Clinic Diet now supports your journey with a special Companion program for weight-loss medication.Keeping your weight in check sometimes can be a lifelong challenge.Wegovy® is initially started at 0.25 mg weekly, in four-week intervals, until the 2.4 mg dose is attained .The NHS in England currently prescribes weight loss medications to patients living with obesity who meet specific criteria.Therefore the decision to initiate drug therapy in obese individuals should be made after the benefits and risks are considered.Setmelanotide is being studied in ongoing phase 3 trials of patients with rare genetic disorders,228, 229, 230, 231 and an ongoing phase 2 trial in 15 patients with hypothalamic obesity.232 ∗ Unless combined with GLP-1, it is unclear that GIP receptor agonism alone reduces hunger and reduces body fat. Analogues of glucagon-like peptide 1 serve as receptor agonists (GLP-1 RA) that are used to treat obesity, either alone or as a component of combination therapy. 9 shows illustrative consequences of early versus late weight management interventions (see Chart 1). A normal BMI is 18.5–24.9, an overweight BMI is 25.0–29.9, and an obese BMI is 30.0 or greater. BMI is a number calculated from a person's weight and height. The product is intended for dogs that are at least 20% overweight.1 This study found that most outcomes had high to moderate certainty evidence, particularly for psychiatric and safety-related results. These results emphasize the significant advantages of tirzepatide in improving cardiometabolic health. Regarding cardiometabolic effects, high to moderate certainty evidence suggested that tirzepatide had the strongest antihypertensive effect and best reduced triglycerides, fasting glucose, insulin, and glycated haemoglobin levels. This finding aligns with Shi et al.,30 who observed greater weight reduction with phentermine/topiramate than with naltrexone/bupropion. Future research in this field will require more high-quality, rigorously designed studies to further validate our findings (Supplemental Appendix 5). “However, to confirm these findings, we need studies in the lab because, at the moment, it’s (based on) reporting from patients.” Results from other studies haven’t found a link between semaglutide and suicidal thoughts. They didn’t find a causal link, however, and reports could be related to other factors such as taking a high dose or existing mental health issues, says Garguis. STAT Plus: At JPM 2026, Mehmet Oz and top Trump health officials explain their thinking to hospital leaders All stakeholders have an important role to play in ensuring that people living with obesity have access to effective medications as a core benefit of health care insurance coverage in ways that do not exacerbate health care inequities. The model may not include the full potential impact of weight loss, as the impact of treatment on some conditions related to obesity was purposefully excluded because of concern over the double counting of weight loss benefits. Because the chronic management of obesity is likely to require lifelong pharmacotherapy for most people, the lack of long-term follow-up reduces certainty in long-term efficacy, harms, and potential off-target benefits, such as a decrease in cardiovascular events with GLP-1 agonists, as seen in the treatment of diabetes. All interventions had greater discontinuation because of adverse events than placebo in an NMA, although semaglutide appears to have lower rates of discontinuation than the other drugs. Whilst the economic cost of obesity is substantial, the personal cost is often greater with an increased risk of multiple medical and mental health complications. In this article we review the efficacy of the currently approved drug therapies and discuss future potential drug mechanisms and early clinical trial results exploring these budding avenues. In a prospective evaluation of a multidisciplinary weight loss clinic for transplant candidates at the University of Cincinnati, 0/52 patients (90% with kidney failure on hemodialysis) were able to achieve sufficient weight loss over 6 months to be eligible for transplantation (86). If obesity increases risk of kidney failure via hypertension and diabetes, then other risk factors (some unmeasured) might be expected to be greater in non-obese individuals with kidney failure(77). There remains controversy about the role of weight loss interventions in patients with kidney failure (31, 73, 74). There isn’t a lot known about how well it works to switch from one of these drugs to another. While these two drugs work similarly, there are differences. The out-of-pocket cost for all of these drugs is about $1,000 per month. Mounjaro, Ozempic, Wegovy, and Zepbound work in similar ways for weight loss. For dose escalation, immediate-release phentermine/extended-release topiramate at 11.25 mg/69 mg can be prescribed daily for 2 weeks followed by a final titration to a dose of 15 mg/92 mg daily for 12 weeks. A study conducted by Ryder and colleagues compared adolescents prescribed phentermine plus standard-of-care lifestyle therapy versus standard-of-care lifestyle therapy alone. Orlistat was approved in 1999 for adults but was not approved for use in adolescents until 2003. The 2017 Endocrine Society Guidelines suggest pharmacotherapy for adolescents if a formal lifestyle modification program fails to limit weight gain or to ameliorate comorbidities. We will also discuss current limitations and next steps in the exploration of future treatment options. There’s also some evidence Zepbound might lead to more weight loss. If you are considering one of these versus the other for weight loss, ask your doctor which one they recommend for you and why. They’re approved if your BMI is over 30 or if it’s over 27 and you have another related health condition. Therefore, cannabinoid receptor antagonists represent a further therapeutic option in the treatment of obesity. Further trials exploring the combination of the NPY inhibitor and orlistat were also disappointing and have been discontinued . We were unable to identify any current clinical trials exploring ghrelin antagonism under progress, though recently ghrelin receptor inverse agonists have been successfully profiled in humans . Some of the reported adverse effects of liraglutide are primarily mild to moderate nausea and diarrhea. To increase the duration and effectiveness of the drug, a different GLP-1 receptor agonist with a longer half-life than exenatide was highly sought, leading to the development of liraglutide. Recently, many GLP-1 receptor agonists, early designed for T2DM management, have received approval for obesity treatment. 7. Naltrexone HCl/bupropion HCl extended release A phase 2 study found that the medication helps improve glucose tolerance in adults with prediabetes. But, if needed, medication is another way to help promote weight loss. When possible, a nutritious diet and routine exercise are ideal ways to lose body weight. Still, some internal or external factors may be driving you to try to lower your body weight. Clinicians are still hesitant to prescribe these medications due to concerns about adverse events, but this approach should be reconsidered, as obesity should be treated as a disease with an individualized management plan for the individual patient. Especially recently developed incretin-based drugs semaglutide and tirzepatide result in dramatic reductions in body weight comparable to bariatric surgery (Fig. 1). At least 5% weight loss is required to prevent obesity-related complications, and it is reflected in the guidelines for weight management drugs. Preclinical studies show that it reduces body weight by increasing energy expenditure and reducing food intake compared to the maximally effective dose of semaglutide (Zimmermann et al., 2022). Currently, CagriSema is undergoing phase 3 trials in people with overweight or obesity and various related conditions (Table 4). Particularly, biomarkers of acute pancreatitis—amylase and mainly lipase—increase in a non-dose dependent manner during treatment with GLP-1 receptor analogs. Particularly, HbA1c (−0.30%±0.28%) and fasting glucose levels (−7.1±0.8 mg/dL) were significantly reduced in subjects administered liraglutide 3.0 mg compared to placebo. Liraglutide was approved base on the results of three main RCTs; The SCALE Obesity and Prediabetes, the SCALE Diabetes and the SCALE Maintenance 58,60,61. EQUIP and CONQUER were each one-year, randomized, double-blind, placebo-controlled studies comprising 1,267 and 2,487 participants, respectively 41,42. Topiramate, a gamma-aminobutyric acid agonist, glutamate antagonist, and carbonic anhydrase inhibitor, was approved for the treatment of epilepsy and prophylaxis of migraines . While these medications are sometimes prescribed in isolation, some clinical studies have reported better outcomes upon combining them with lifestyle changes. Past research also suggests that long-term use of such medications may result in more severe side effects such as hypoglycemia (low blood sugar), pancreatitis, and C-cell hyperplasia, a potential precursor to medullary thyroid carcinoma 7, 11. In this case, synthetically produced GLP-1 receptor agonists can substitute for intrinsically available GLP-1 receptors in patients with diabetes. Research published in nutrition journals indicates that best time to eat for weight loss varies by individual, but consistent meal timing supports metabolic regulation and appetite control. Research consistently demonstrates that reducing caloric intake while maintaining adequate nutrition supports weight loss. These evidence-based approaches form the foundation of all legitimate weight loss programs and medical interventions. When medical professionals discuss effective weight loss, they consistently point to strategies supported by extensive clinical research. Medical professionals view weight management as a long-term health commitment rather than a temporary intervention. Mean change in body weight was -13.3% with semaglutide and -2.6% with placebo over 52 weeks. In the STEP 2 trial, conducted in adults with obesity and T2D, HbA1c levels at 68 weeks were reduced by -1.6% in the semaglutide 2.4 vs. -1.5% in the semaglutide 1.0 vs. -0.4% in the placebo group, and 78.5%, 72.3%, and 26.5% achieved an HbA1c89). The SELECT trial builds upon an established body of evidence (e.g., SUSTAIN-6) demonstrating the CV safety and benefits of semaglutide and is groundbreaking as the first CVOT to demonstrate secondary cardiovascular prevention with an anti-obesity medication in a population without T2D. In March 2024, semaglutide 2.4 mg received FDA-approval for the treatment of CVD in adults with preexisting CVD and obesity or overweight. The phase 3 RCT, STEP 8, randomized adults with obesity without T2D to liraglutide 3.0 mg/d or semaglutide 2.4 mg/wk or respective placebos (94). For expensive GLP-1 medications that may cost $1,000 or more monthly, this cap provides substantial financial protection.Obesity is recognized as a major pandemic of the 21st century, contributing to increased morbidity, mortality, and the burden of healthcare costs (1).GLP-1 medicines should not be taken by people who are breastfeeding.Many over-the-counter remedies can have major effects on your health in ways you might not predict.They didn’t find a causal link, however, and reports could be related to other factors such as taking a high dose or existing mental health issues, says Garguis.A sensitivity analysis excluding studies with a high or medium risk of bias was also conducted.The drugs are delivered through once-weekly injections.Medicines to help with weight loss have been prescribed for many years.It’s less common than other weight-loss pills, though. Lilly to advance alternative obesity candidate to phase III. For future fills and for other Wegovy doses, pay $349 per month for the injection and $299 per month for the pill. Some are only meant for short-term use, while others can be used for weight management over time. The study should be wrapped up by early 2026. MariTide is being studied for chronic weight management. Sleep disorders have been reported in a significant number of patients taking naltrexone ER/bupropion ER; thus, the deterioration of existing sleep disorders or development of newonset sleep disorders should be monitored when the drug is administered. However, because there is less interaction with antidepressants, liraglutide should be considered first for patients taking antidepressants. Although liraglutide has no effect at a low dose, at a high dose, mood disorders worsen slightly. Talk to your doctor about your weight loss and health goals and whether this may be a safe option for you to consider. These drugs are generally considered safe, but they do have possible side effects. But we need more research to really understand the differences over the long term and how taking either one of these drugs affects your health. The side effects of both drugs also were similar. It turned out that people taking tirzepatide lost more weight than those taking semaglutide. Several ongoing trials investigate the role of FDA approved AOM in patients with obesity and specific conditions (Table 4). The Viking Trial extended over 24 weeks and enrolled 372 participants, randomized to Tesofensine 0.25 mg or 0.5 mg or placebo.170 There was on average 10% total body weight loss at 24 weeks in the intervention arm, and no significant adverse events.170 However, the peer-reviewed publication of the trial has not been available online yet. Small trials on NB and Phentermine/Topiramate have shown some safety and efficacy on total body weight loss. The data on the safety of phentermine/topiramate in participants with a history of depression or on anti-depressive medications was derived from the main trials that did not reveal any signal for increased risk of adverse events.64, 65, 66 In a post-hoc analysis from the LIGHT trial, in the sub-group of participants who were on anti-depressants, the adverse events related to mental illness/depression were similar in NB and placebo arms.120 A pooled analysis of Liraglutide trials, on participants with psychiatric diseases (depression and others) showed a signal for increased suicidal ideation, but no increase in the incidence of mental diseases. As per the FDA leaflets, uncontrolled hypertension is a contra-indication for the use of Phentermine and NB; arrhythmias are also a contra-indication for the use of phentermine and tachycardia is listed under adverse events for NB.68,74 For liraglutide and semaglutide, increased heart rate is considered under “Warning and Precautions”, with a suggestion to monitor as the clinical implication of the increase in heart rate by few beats per minutes is not known.16,81 No adverse effects related to heart rate were reported with Orlistat.63 For other cardio-metabolic co-morbidities, such as OSA, DM and CVD, the suggestion for AOM take into consideration the safety and/or direct or indirect evidence on efficacy with specific drugs. Contrave side effects The mean percent weight loss was 13% in the 0.4-mg group vs 1% in the placebo group.Additional cardiovascular protection has been proven in heart failure with preserved ejection fraction (HFpEF).Another phase 2 trial compared three doses of cetilistat (40, 80, and 120 mg three times a day) with a placebo for 12 weeks in obese patients with T2DM who were taking metformin.A study to test whether survodutide (BI ) helps people living with overweight or obesity who also have diabetes to lose weight (SYNCHRONIZE-2).Some people can develop an immune system reaction to exenatide.Based on evidence discussed above, it can be argued that semaglutide indeed blocks the normal feeding response to weight loss (Figure 1).There was one study conducted in the Australian setting that used disability-adjusted life year (DALY) as a measure of health loss (62).The COR-I trial randomized 1.742 patients for NB16, NB32 or placebo, with four weeks of titration of medication and a duration of 56 weeks . Examples of drugs administered as salts include phentermine HCl, naltrexone HCl, and bupropion HCl . While capsules can also be manufactured for immediate, delayed, or extended release, capsules also allow for fat-soluble drugs to be mixed with oil upon administration, which may enhance absorption . While capsule formulations cannot be split, they can be easier to swallow and are often used to protect drugs from degradation in the acidic environment of the stomach. What are legitimate alternatives to unproven weight loss compounds? Measurement of body weight and height to determine BMI is commonplace, and BMI has strong, consistent associations with health outcomes in the general population(6). More research is needed assessing long-term cardiovascular and kidney outcomes of most weight loss medications. While body mass index is typically used to assess obesity in clinical practice, altered body composition (e.g. reduced muscle mass, increased visceral adiposity) are common among patients with CKD. The FDA has issued warnings about compounded GLP-1 drugs because of reports of harmful side effects. Dietary supplements for weight loss However, evidence suggests that short-term treatment (3 to 6 months) with weight-loss medications does not produce long-term health benefits (Garvey et al., 2016); therefore, this review focuses on long-term weight-loss anti-obesity medications. Recently developed drugs and those currently under development have been shown to reduce body weight by more than 10% and are expected to reduce obesity-related complications. If you are interested in exploring weight-loss medications, it is essential to work closely with an experienced healthcare provider to determine if it is the right treatment option for you. Finally, you'll need to consider with your doctor whether the risks of these drugs (which range from heart problems and liver damage to possible addiction) are worth the weight you'll lose. With the potential use of myostatin inhibitors in patients with SMA on the horizon, this is now accelerating into efforts to target myostatin for obesity. Based on the results of these trials, one of these companies, Scholar Rock, is now seeking FDA approval for their myostatin inhibitor, which is based on a fundamental mechanism discovered by Lee by which myostatin is regulated. Following a 1-week placebo lead-in, 244 obese or overweight, nondiabetic received placebo subcutaneously (sc) tid, or pramlintide sc, 120 mcg tid, either isolatedly or in association with sibutramine, 10 mg/d, or phentermine, 37.5 mg/d, for 24 weeks. Four patients had already left the study due to nausea in the initial weeks of pramlintide titration. Recently, a qualitative review aimed to identify healthcare professionals’ perceptions towards obesity management and therapy across 15 previous studies.This weight regain can also trigger a return of internalised stigma, as individuals may feel renewed failure and shame over their inability to maintain weight loss without ongoing medication.Resveratrol is credited with a series of antioxidant, anti-inflammatory, cardioprotective, and anti-obesity properties.Ozempic and Wegovy are really the same drug, but you will take them in different doses.Empagliflozin (Jardiance) was approved for the treatment of people with T2D by the EMA and the FDA in 2014.The study showed that the phentermine plus standard-of-care lifestyle therapy resulted in statistically significant reductions in weight and percent BMI at 1 month (−1.4 kg, −1.6%); 3 months (−2.6 kg, −2.9%); and 6 months (−3.2 kg, −4.1%) compared with standard-of-care lifestyle therapy alone.13 Viking Therapeutics announces positive top-line results from phase 2 Venture trial of dual GLP-1/GIP receptor agonist VK2735 in patients with obesity. Novo flunks kidney disease trial, again linking obesity prospect to neuropsychiatric side effects. Oral GLP-1/GIP dual agonist VK2735 achieves up to 12% weight loss in phase II Venture trial. Off-label drugs for weight management. This is because your body may not absorb HRT while using tirzepatide. This is because your body may not absorb the contraceptive pill during this time. Tirzepatide is not recommended if you're pregnant or planning to get pregnant, breastfeeding, or if you have certain health conditions. Semaglutide is not recommended if you're pregnant, trying to get pregnant or breastfeeding or have certain health conditions. As no concern regarding neuropsychiatric safety was reported, this medication can serve as a good option for obese patients with mental disorders if they can afford this costly medication (liraglutide 3.0 mg) and agree to a daily injection. A phase IIIb RCT reported no difference in calcitonin levels and medullary thyroid carcinoma rates between liraglutide (≤1.8 mg) and placebo during a follow-up of 3.5–5 years . In rodents administered incretin-based medications, pancreatic, intestinal, and breast neoplasms were found to develop more frequently; however, these results were not found in human studies 66,67,68. Improvements in systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides, and high-density lipoprotein (HDL) cholesterol were seen in subjects treated with phentermine plus topiramate compared with placebo in both EQUIP and CONQUER (26,27). Multiple Phase 1, 2, and 3 studies including more than 5000 subjects have evaluated the efficacy and safety of phentermine/topiramate combination therapy. A carbonic-anhydrase inhibitor, topiramate was found to stimulate lipolysis in preclinical studies (62). Administration of orlistat with psyllium mucilloid reduced the incidence of GI side effects to 29% with psyllium vs. 71% without psyllium (58). The gastrointestinal side effects of orlistat, including fatty/oily stool, fecal urgency, oily spotting, increased defecation, fecal incontinence, flatus with discharge, and oily evacuation (48), are the main reasons for discontinuation of therapy. In total, there are currently only eight drugs (see Table 1) FDA approved for the treatment of obesity.15 Six of these drugs have received FDA approval just in the last 20 years. Childhood obesity can track into adulthood and obesity increases the risk of diabetes and cardiovascular disease.9 Pharmacotherapy for weight loss in the pediatric population are much more limited than in adults. The Addiction study does not prove that GLP-1 medications directly lower the risks of opioid overdose and alcohol intoxication, only that people taking them seemed to be helped. You should only use weight loss drugs if you plan on keeping regular checkups with your healthcare provider. The decision to begin weight loss drugs should only happen after you and your provider discuss your health history. For instance, a study found that more than half of respondents who underwent rhinoplasty did so due to social media “before and after” advertisements . The prevailing approach for weight management is through a combination of diet, exercise, and pharmacotherapy . However, future studies should address these links as they pertain to specific diseases and illnesses in clearly defined contexts. It is possible that other factors such as socioeconomic status, access to preventative care, and epigenetics may play a larger role in disease risk. Federal law specifically prohibits Medicare Part D plans from covering medications prescribed solely for weight loss purposes."I'm pretty much willing to go through some serious side effects if I had to," she said.In terms of eating behavior, liraglutide (3.0 mg for 5 weeks) also increases feelings of both satiety and fullness and decreases feelings of hunger and prospective food consumption compared with a placebo .A VLCD induces a larger short-term weight loss than a does a standard 1500–1800-kcal/d diet (2), although there is also more regain (1, 2).That approaches what people can lose with weight-loss surgery.Both Wegovy and Mounjaro require weekly injections, which many people find unpleasant.One trial recently reported that oral semaglutide (14 mg once daily) resulted in greater weight loss compared with subcutaneous liraglutide (4.4 kg vs. 3.1 kg) over 26 weeks . Dose escalations are weekly, and the drug administration is daily via subcutaneous injection.33,55 Liraglutide should not be used in patients who are pregnant, have personal or family history of medullary thyroid carcinoma or type 2 multiple endocrine neoplasia. When starting treatment with Contrave, a four-stage dose-escalation regimen is followed by a dose increase every 7 days. The standard treatment plan for Qsymia involves a four-stage dose escalation starting with immediate-release phentermine/extended-release topiramate 3.75 mg/23 mg once daily for 2 weeks followed by 7.5 mg/46 mg once daily for 12 weeks. 3.4. Most common adverse reactions Overall, 151 (98.1%) studies showed a low or medium risk of bias (Figure S1 in Supplementary Appendix 7). We employed the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system to assess the certainty of the evidence for each pooled analysis, classifying the results as “high,” “moderate,” “low,” or “very low” (Supplementary Appendix 4).29, 30, 31 Initially, the GRADE approach considers all randomised control trials as high-quality evidence. A sensitivity analysis excluding studies with a high or medium risk of bias was also conducted. Sensitivity analyses were conducted by omitting each study individually and recalculating the pooled effect size estimates for the remaining studies to evaluate the impact of individual studies on the pooled results. To investigate the effects of each weight-loss medication on these distinct patient groups, we performed stratified analyses. Especially when combined with reduced mobility or a decrease in the ability to engage in recommended physical activity (e.g., those with brain dysfunction or injury), hypothalamic dysfunction can substantially contribute to positive caloric balance and increased body fat . Beyond the potential for high fat food intake to promote hypothalamic inflammation , managing obesity due to hypothalamic trauma, surgery, or dysfunction is often challenging. Table 4 describes challenges with past anti-obesity pharmacotherapies. Orlistat is contraindicated in patients with chronic malabsorption syndrome or cholestasis, and in patients with known hypersensitivity to orlistat or to any component of this product. However, the larger issue is that many people see the new drugs as a quick-fix solution. "But there isn't enough evidence to know whether these drugs might be beneficial or dangerous for people who fall outside of the FDA criteria," says Dr. Caballero. Still, that has not stopped some doctors from prescribing these medications "off-label" for weight loss, which means they are used for a different purpose than explicitly intended. Although liraglutide was not the most effective for weight loss or cardiometabolic improvement, it significantly reduced the risk of MACEs in patients with weight-related complications, similar to semaglutide, indicating strong cardiovascular protective effects. A 2013 systematic review identified 6 lifestyle intervention randomized controlled trials (RCTs), 1 pharmacologic RCT, and 24 observational studies examining the effect of intentional weight loss on kidney parameters in patients with obesity and altered kidney function (24). Use of medications that promote weight loss with favorable cardiovascular risk profiles should be promoted, particularly in patients with type 2 diabetes, obesity, and CKD. According to FDA regulations, a product should result in at least 5% mean weight loss, which indicates a statistically significant effect compared with the placebo group, and more than 35% of patients should achieve 5% or greater categorical weight loss after 1 year of treatment to be defined as an effective anti-obesity drug . In the XENDOS (XENDOS (XENical in the prevention of Diabetes in Obese Subjects) trial, the largest randomized controlled trial (RCT) that evaluated the effect of orlistat in 3,305 patients, orlistat was found to cause a total body weight loss of 2.4% after 4 years. Recent advances in anti-obesity drugs have enabled the potential of achieving clinically significant weight loss. Anti-obesity, or weight loss drugs can help. Most weight loss medicines are prescription only. Your healthcare provider can help you understand the pros and cons of this treatment and if it’s right for you. Weight loss medications help you lose weight. Supplements are rarely the answer to safe, sustained weight loss. Ephedra (ma-huang) is an herb once used for weight loss. Nearly one in four people who come to our program has undiagnosed disordered eating.” Patients who turn to VCU Medical Weight Loss program are desperate for help and Wolver cares deeply about helping them.“That is what I am passionate about,” she said. “We try to look for root causes and help them with that, whether that be challenges with understanding a healthy diet, being able to implement it, barriers to exercise, mental health issues or disordered eating. There can be less than optimal oversight of this process and some people have been hospitalized. We call that metabolic adaptation,” Wolver said, adding that when someone starts to lose weight, hunger increases, and metabolism slows over time. Current research suggests that GLP-1 receptors are present throughout the body; hence, its effect extends beyond glycemic control . Like the GLP-1 enzyme, GLP-1 receptor agonists can suppress appetite, delay gastric emptying, reduce plasma glucose levels, and enhance insulin secretion, thereby controlling glucose levels in the body . In the same way, GLP-1 agonists bind to GLP-1 receptor sites and trigger the same effects even in the absence of intrinsic GLP-1 molecules. Beyond this, studies have also begun comparing different GLP-1 agonists, including increasingly popular tirzepatide (a dual GLP-1/glucose-dependent insulinotropic peptide (GIP) agonist) and danuglipron. As an oral medication, a 14 mg daily dose of Rybelsus® is equivalent to the 0.5 mg weekly dose of Ozempic® . “A doctor can write down pancreatitis and there it is on the health-care claim. It relies on diagnoses recorded on health-care claims, which might not always be accurate. But the study has an important limitation, says Daniel Drucker, an endocrinologist at the University of Toronto in Canada. Its tendency for resistance limits it, but it is a valuable target for patients with obesity related to leptin deficiency, hence the significance of metreleptin. GLP-1 receptor agonists, such as liraglutide and semaglutide, stimulate insulin secretion, inhibit glucagon secretion, and delay gastric emptying, serving as appetite suppressants. Some people may succeed with the first medication, while others may need to try different medicines to find one that works for them with minimal side effects. Perhaps, it’s wanting to improve your body image.The pharmacoeconomic evidence on anti-obesity drugs has been emerging in several reviews which primarily focused on either pharmacologic treatment or various interventions (47, 48).Randomized controlled trials have shown that topiramate is both tolerable and effective in promoting weight loss (61).It is worth noting that with regard to the drugs in initial studies, much of the information and clinical outcomes are from the pharmaceutical companies own websites, since they have not been yet submitted to peer-review in medical journals.Some reviews suggest that girls and women are affected most facing significant consequences like wage penalties and employment barriers, in particular for those women with both obesity and higher socioeconomic status .Although some studies have shown exenatide promotes weight loss, it is not currently FDA-approved specifically for obesity treatment.7 weight loss tips to shed pounds and keep them off for goodThis is because your body may not absorb the contraceptive pill during this time. Although uncommon, weight-loss medications also can cause other serious side effects, including an inflamed pancreas (pancreatitis), gallstones, kidney problems, or allergic reactions. Some weight-loss drugs work by slowing down digestion. As with most medications, weight-loss medications may come with side effects. Obesity is linked to a number of health problems, most prominently type 2 diabetes, a disorder where the body doesn’t process blood sugar. It's the first way to activate brown fat without cold exposureMybetriq also may not be ready for prime-time as a weight loss drug. Saxenda side effects Beneficiaries must have a BMI of 35 or higher plus at least one obesity-related health condition, such as diabetes, high blood pressure, or sleep apnea. For diabetes management, plans often require attempting metformin or other first-line treatments before approving GLP-1 medications. The prior authorization process requires doctors to submit medical documentation proving the medication is medically necessary for the approved indication, not weight loss. The most common side effects are dose-related GI issues like nausea and diarrhea, plus modest increases in heart rate. Rapid weight loss can include some lean-mass loss. Questions surround their effects on brain health, pregnancy or long-term use. Newer versions of that drug were shown to have even bigger effects. Ozempic, Wegovy, and other similar drugs are known as GLP-1 agonists; they mimic a chemical made in the intestine, GLP-1, that increases insulin and lowers blood levels of glucose. “A dramatic adjustment of body weight can trigger biological and psychological responses that can influence suicidal ideation,” says Amira Guirguis, a professor of pharmacy at Swansea University in the UK. Other worrying side effects being reported are mental health problems such as anxiety, depression and suicidal thoughts. A weekly dose of semaglutide not only suppresses your appetite, but also delays the rate at which food leaves your stomach, helping you to feel full for longer. In some cases, semaglutide has led to malnutrition, gastric issues, mental health issues and eye problems. In this article we have highlighted important clinical trial data that support the pharmacotherapy of obesity. Importantly, topiramate should not be combined with other drugs that inhibit carbonic anhydrase. However, it exerts weight reduction effects through increased satiety, increased energy expenditure, reduced caloric intake, and taste abnormalities. Topiramate is a gamma-aminobutyric acid agonist, glutamate antagonist, and carbonic anhydrase inhibitor that is used to treat epilepsy and prevent migraines, although its mechanism for obesity treatment is uncertain (Fig. 1) 35,36. The drug is contraindicated in patients with severe hepatic dysfunction or end-stage renal failure . As a result, bupropion inhibits food intake via the reward system and increases energy expenditure for weight reduction . Bupropion is a norepinephrine and dopamine reuptake inhibitor that is used for depression and smoking cessation treatment. In patients with chronic malabsorption syndrome or cholestasis, as orlistat can reduce the absorption of fat-soluble vitamins (i.e., vitamins A, D, E, and K), multivitamin supplementation might be needed. Constipation can be treated by orlistat, along with dietary fiber supplementation, via its gastrointestinal side effects. The side effects experienced by more than 20% of participants who use orlistat for 2 years include fecal incontinence, oily spotting, and fatty stool. It could be argued that the short duration of placebo-treatment is insufficient to evaluate weight loss, as many patients relapse and thus have withdrawn from the study.Ozempic, for example, was meant to help people with type 2 diabetes.Edits were made in response to reviewer comments and the final revised manuscript was approved by all the authors prior to publication.If days to weeks after start of topiramate, a patient experiences myopia and signs/symptoms of glaucoma, and if a diagnosis of drug-induced angle closure glaucoma is made, then discontinuing topiramate may result in recovery within one week if the glaucoma was due to the topiramate 93,94.This medical indication enables potential Medicare coverage when the medication is prescribed to address sleep apnea rather than weight management.We need more data on the long-term effects and other outcomes related to cardiovascular health, particularly in lower-risk individuals.Here are the most common side effects and helpful tips to help manage them.Significant changes to Medicare Part D in 2025 improve affordability for beneficiaries requiring expensive medications, including qualifying weight loss drugs.Weight-loss pills are a convenient needle-free option for people who need help losing unwanted body weight. In addition, in many studies, authors solely listed specific variables or scenarios for analysis without giving detailed justification for selecting a specific parameter for the sensitivity analysis in advance. More than half of these studies performed both deterministic and probabilistic sensitivity analyses (51–55, 58–61, 64, 69). Sensitivity analysis was carried out in all the studies in full text to check the robustness of the base case estimates. Moreover, time horizon and discount rates were estimated at values different from the base case in the sensitivity analysis to investigate the parameter uncertainty in some of the studies (51, 52, 54, 58, 59, 61, 65, 67, 68, 70, 71). Three studies performed their evaluation from a societal perspective (53, 63, 65). Notably, weight loss can improve insulin levels, reduce androgen levels, and lead to improvements in ovulation and fertility. Regardless of which condition came first, if you’re living with obesity and have PCOS, losing weight can improve your symptoms. And the hyperandrogenism (excess male hormones) that goes along with PCOS may lead to overweight and obesity. Many of these drugs are also targeting receptors of GLP-1, as well as other hormones involved in satiety and metabolism, but some are using entirely novel mechanisms. More than 170 drugs are now in the tracker. Additionally, the health care professionals presented the new medication with a clear moral undertone, questioning patients’ motivations for wanting the drug and emphasising individual responsibility for lifestyle changes. The results showed that a woman losing weight using obesity medication was more negatively evaluated and judged to have taken a “shortcut” to achieve weight loss. The intervention study examined how potential negative public perceptions about individuals who use the new weight-loss medication for obesity operated . The search resulted in 310 publications but only two of the publications were empirical studies that addressed stigma related to weight management using the new medications. Some studies, on the other hand, found an increased risk of cancer in these patients with long‐term use. These findings suggest a potential long‐term side effect of these medications, especially as the same association was not found with other anti‐diabetic or weight loss medications. Analysis of individual drugs revealed that all showed higher numbers of papillary thyroid cancer cases, except for semaglutide and dulaglutide, which exhibited comparable rates of papillary and medullary thyroid cancers (Table 3). The interim commissioning guidance outlines NHS England’s approach to implementing this medication into the weight management pathway. A phased approach allows NHS England to build an evidence base for sustainable and effective delivery of weight management services. NICE has directed NHS England to prioritise a cohort of 220,000 patients, based on clinical need, over the first 3 years of a 12 year rollout. NICE has agreed that a funding variation is required to facilitate a phased introduction of delivery to eligible cohorts, manage the demand on primary care services and train healthcare professionals. Previously, GLP-1 receptor agonists (Wegovy® and Saxenda®) could only be prescribed in secondary care for the management of obesity. For example, the European Court of Justice recognizes obesity as a disability and UK disability laws require employers to make reasonable accommodations for employees with obesity to prevent discrimination. Similar to protections under the ADA for HIV/AIDS, obesity should be listed as a protected characteristic within anti-discrimination laws in EU and other countries. In EU, the European Court of Justice ruled in 2014 that while obesity itself is not a protected characteristic under EU anti-discrimination law, severe obesity can in some cases be considered a disability if it causes long-term physical, mental or psychological impairments . In the UK the disability laws require employers and employees to not discriminate or harass their colleagues with obesity and to provide reasonable adjustments in the workplace where discrimination is a possible outcome of behaviors or policy arrangements . The evolution of stigma surrounding AIDS before and after the antiviral treatments, illustrates how societal attitudes towards medical conditions can change . Although the three evaluations included were conducted in different settings, the cost-effectiveness of this newly approved GLP-1 drug for long-term weight management based on the Core Obesity Model was consistently promising. This development process of these critical weight loss therapies benefits from the recent advances in the understanding of the pathophysiology of obesity as a complex disease and the metabolic processes (74). Cohort-based Markov model was commonly applied to conceptualize a series of health states in relation to obesity and transitions between the states in most of the studies (51–53, 61–64, 67, 68, 70, 71). The decision to initiate drug therapy in an obese individual should be made after the risks and benefits are considered. To date, however, there has been no approved combination agent for obesity management, besides phentermine/topiramate and naltrexone/bupropion. As obesity occurs via multifactorial pathways, a single drug might exhibit limited efficacy. Indirect mean and categorical weight loss comparisons show that semaglutide (13.7%) and phentermine/topiramate (9.1%) achieve a greater percentage average weight loss than liraglutide (5.0%) and bupropion/naltrexone (4.6%). Since most people do not achieve the desired weight loss with lifestyle modification, medications and surgical interventions are often considered. Obesity is a common chronic disease that increases the risk of many other health conditions affecting morbidity and mortality, such as diabetes and heart disease.1,2 Social stigma can make individuals with obesity feel judged, shamed, and ostracized.3 Often starting in childhood, obesity can also affect educational development, social interactions, relationships, and work.4,5 The study also confirmed past research findings detailing the drugs' potential to lower the risk of heart attack, stroke and other cardiovascular concerns. People taking the weight-loss drugs also experienced decreased risks of suicidal ideation, self-harm, bulimia and psychotic disorders such as schizophrenia. All anti-obesity medications are contraindicated in patients with hypersensitivity to the drug (e.g., anaphylaxis, angioedema), and should not be used in patients with overweight/pre-obesity or obesity who are pregnant or planning to become pregnant. Many people with diabetes who are prescribed metformin lose around 2% to 3% of their body weight within the first year of starting the drug. The introduction of effective weight loss medications, like the GLP-1 receptor agonists, in addition to providing a realistic method to manage weight has the potential to reduce both internalised and externalised stigmatisation of people living with obesity. Some weight-loss supplements have been found to have ingredients that aren't listed on the label, such as prescription medicines. Results from such a trial would show more about the product safety and how well it worked. It would be ideal if these first results had been tested in a much longer trial. You start with a 0.25 milligram dose for the first month then increase that to 0.50 milligrams. There are no approved generic versions of Wegovy, despite what you may see advertised. That’s according to a small clinical trial run by Novo Nordisk, so real-life results may vary. Terminated early as sponsor decided to develop controlled-release formulation; results presented for modified-intention-to-treat analysis of 229 patients completing 10-month follow-up While visceral adiposity is best captured by imaging, elevated waist circumference (≥102 cm for men, ≥88 cm for women) is a simple alternative that captures some of this risk(11, 13). In contrast, lower-body subcutaneous fat may serve as a metabolic buffer, preventing other tissues from accumulating lipotoxicity (10). Another important issue is heterogeneity in fat distribution as visceral fat has more adverse metabolic effects than subcutaneous fat (9). First, BMI is a poor metric for body fat distribution and is unable to differentiate between fat and muscle mass. Several observational studies have compared long-term kidney function outcomes in patients who undergo bariatric surgery to matched non-surgery patients with severe obesity(5, 69-71).Prescribing information of weight loss drugs approved by the FDA in combination with lifestyle modificationsThe blazing success of weight loss drugs like Wegovy and Mounjaro has electrified the pursuit of new treatments for obesity.The reduction in apnea-hypopnea events was more favorable in patients taking phentermine/topiramate compared to placebo; a reduction of 31.5 (19.9) events per hour in the intervention and 16.6 (19.9) events per hour in the placebo (p 0.0084).105The average weight loss was 0.1 kg, 2.1 kg, and 5.6 kg in the placebo, metformin, and ILI groups, respectively (P14).Most studies on obesity stigma were from Western societies, where stigma surrounding obesity may be linked to moral teachings and norms rooted in Christian, particularly Protestant, traditions. These drugs are long-term drugs, meaning you may have to be on them the rest of your life.“When you stop the meds, you can rapidly regain weight,” Wolver said. People can't go on the drugs for a short amount of time, lose weight, and then promptly stop taking the medication. A study on Zepbound showed a more significant weight loss of 21%, “which is substantially more than you can expect to get from lifestyle alone,” Wolver said. Some people might believe these drugs are the “magic bullet” they have been waiting for. Most Medicare Part D plans require prior authorization for expensive weight loss medications, even when prescribed for covered indications. Wegovy (semaglutide) gained FDA approval for reducing cardiovascular death, heart attack, and stroke risk in adults with established cardiovascular disease who are overweight or obese. These medications help control blood sugar levels while often producing weight loss as a secondary benefit. For detailed information about Medicare coverage options for weight loss medications, guidance is available to help beneficiaries understand their specific plan benefits and requirements. Federal law specifically prohibits Medicare Part D plans from covering medications prescribed solely for weight loss purposes.