WHO reports that more than 1 billion people worldwide are obese, putting them at increased risk of worse health outcomes. We included only studies pertaining to adult patients that have been published between 2012 and 2022. Finding adequate prevention and treatment options would therefore lead to massive improvements in the duration and quality of life of affected individuals. Many people regain most of the weight within 2 years after they stop using it. But not everyone loses weight while taking it. The different weight-loss medicines are described below. Analyses from the most recent National Healthand Nutrition Examination Survey from 2015–2016 estimated that 39.6% of USadults are obese (body mass index BMI ≥30 kg/m2), compared to33.7% in 2007–2008 and 7.7% of adults are severely obese (BMI ≥40kg/m2), compared to 5.7% in 2007–2008 . Naltrexone/bupropionresults in an increase in in-office and ambulatory blood pressure comparedto placebo. Additionally, we offer resources on nutrition and lifestyle adjustments to support customers in addressing weight management comprehensively. VitalMeds is all about making your weight loss journey redefined and simplified! Your healthcare provider will create a personalized treatment plan designed just for you. Maybe you want to boost your health or get in shape for a vacation. What will give you the burning desire to stick to your weight-loss plan? No one else can make you lose weight. All GLP-1 and dual-agonist medications are prescription-only in the UK.The pharmacological treatment of obesity is a fast-changing landscape, and care providers must strive continuously to stay current.Phase 2 studies have used four different doses of orforglipron (12, 24, 36, and 45 mg); at week 26, the mean weight loss from baseline ranged from 8.6% to 12.6% across the orforglipron dose cohorts compared to 2.0% weight loss in the placebo group.This site is an advertisement for telehealth services, and any treatment or prescription is at the sole discretion of the prescribing provider.Get the latest health tips and articles delivered directly to your inbox.The proposed algorithm for the management of obesity with available long-term anti-obesity drugs is summarized in Fig. Your doctor may be able to lower your dose or change to a different medicine. If you're having problems with side effects, talk to your doctor. And minor side effects sometimes go away after a while. Many people don't have side effects. All medicines can cause side effects. Good Things Utah: Healthy Habits In the last 20 years, the FDA has approved 208 drugs for cancer, 118 for cardiovascular disease, 168 for neurological diseases, and only 6 for obesity. Additionally, one participant showed clinically significant reductions of heart rate, as well as systolic and diastolic blood pressure after weight loss.82 Reported adverse events included dry mouth, skin induration localized at the injection sites and darkening of skin nevi.82 Despite these side effects, setmelanotide has shown the potential in treating genetic-related obesity disorders in children and adolescents. The GLP-1 agonist exenatide is currently FDA approved for the treatment of type 2 diabetes, while liraglutide is also approved for the treatment of obesity in adults, and type 2 diabetes in adolescents and adults.72 Of the available evidence for the use of GLP-1 agonists in pediatric populations, results have shown promise in their feasibility, safety and tolerability for the treatment of obesity and type 2 diabetes. Potential side effects include interference with oral contraceptives and risks for birth defects when taken during pregnancy.71 In previous clinical trials testing combination therapy of phentermine/topiramate in adults, reports of anxiety and depression were deemed a result of topiramate, since it is known to cause reversible cognitive and psychiatric disorders. Although the topiramate group showed significantly decreased very-low-density-lipoprotein cholesterol and visceral fat, no significant differences in weight loss were observed between the two groups.69 In addition to this pilot, a retrospective chart review was done to investigate weight reduction in adolescents with severe obesity treated with lifestyle-modification therapy, in conjunction with topiramate 75 mg daily, for a minimum of 3 months. So your provider will need to check your blood pressure regularly at the start of treatment. Bupropion-naltrexone is a combination drug. It affects the way your body absorbs fat. And ask about the possible benefits and risks of each drug. Mild side effects, such as nausea, constipation and diarrhea, are common. Additionally, phentermine/topiramate CR should be avoided in patients with sleep disorders 67,68. As phentermine/topiramate CR can cause mood disorders, it should be avoided in patients with mood disorders. Little clinical data are available on the effects of phentermine/topiramate ER on eating behavior. In the COR-BMOD trial, there was a significant improvement in the ability to control eating in the naltrexone ER/bupropion ER group compared with the placebo group. Additionally, liraglutide use can cause gallstones and, less commonly, acute pancreatitis 57,58; it should not be used in patients with a history of pancreatitis.It requires a daily injection with a starting dose of 0.6 mg.Body fat reduction in SURMOUNT 1 was 33.9% with tirzepatide administration, compared with 8.2% with placebo administration.Whereas a small degree (2–5%) of weight loss, if maintained for 2years, can significantly reduce the risk of type 2 diabetes among patients withoverweight/obesity and weight loss of 5–10% significantly improvesglycemia in patients with type 2 diabetes, reductions in blood pressure are lesssignificant and vary with mild to moderate weight loss .“Many patients who really benefited from them have had to scramble to get them,” Dr. Obici says.Forced overfeeding studies from America have shown that, despite a group of individuals being overfed by the same amount, there is a range of weight gain.The suggestion for the use of GLP-1 receptors agonist is based on the availability of indirect evidence on cardiovascular risk reduction in patients with diabetes mellitus, LEADER trial for liraglutide157 and SUSTAIN trial for semaglutide.158 There was no signal of increased CVD in patient with obesity on liraglutide. Results from studies that used transgenic GIP-overexpressing mice or that administered GIP to humans show that GIP results in weight loss and improved insulin sensitivity (Hojberg et al., 2009; Kim et al., 2012), suggesting that GIP could be a therapeutic target for obesity. The Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial (Lincoff et al., 2023) was a randomized, placebo-controlled trial. Secondary endpoint results from the STEP trials indicated improvement in cardiometabolic risk factors, including waist circumference, blood pressure, lipids, and C-reactive protein with semaglutide administered at a dose of 2.4 mg, as well as benefits on physical function and quality of life. As a result, GLP-1 receptor agonists (RAs) are an attractive target in the development of drugs for obesity and diabetes. If only one pathway is targeted, as in monotherapy, this can lead to the occurrence of compensatory mechanisms, which reduces drug efficacy; the use of phentermine/topiramate as a combined therapy can overcome these compensatory mechanisms. One clinical trial reported 1.3% weight loss in the placebo group and 6.1% weight loss after NAL/BUP administration at a dose of 32 mg for 56 weeks. NAL monotherapy also has minimal weight loss effects; however, when combined with other weight-loss drugs, it prevents the classic weight loss plateau observed with monotherapies (such as BUP) by blocking β-endorphin-mediated proopiomelanocortin autoinhibition (Greenway et al., 2009). 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. Therefore, the goal of obesity treatment is not exclusively centered on achieving weight loss, but rather on reducing the risk of obesity-related diseases and improving overall health. What Insurance Plans Cover Weight Loss Medication? A study from FAIR Health published in May 2025 reports that more than 2% of U.S. adults took a GLP-1 for weight loss in 2024. The pharmacological treatment of obesity is a fast-changing landscape, and care providers must strive continuously to stay current. However, phentermine inhibits red cell uptake of serotonin so combining it with bupropion may increase circulating serotonin, which has been shown to cause heart valve fibrosis. This is because bupropion has antidepressant effects and may increase cerebral serotonin. Finally, as individual treatment responses to anti-obesity drugs vary, the appropriate classification of patient groups will be the first step toward personalized medicine and the provision of more suitable drug selection and improved treatment algorithms. Although there is no direct evidence regarding the safety and effectiveness of liraglutide 3.0 mg on cardiovascular disease, it is the most preferred drug for patients with obesity and type 2 diabetes mellitus. Furthermore, pharmacogenetic and mechanistic studies to confirm the effects of drugs on feeding behavior and reward processing would allow the further characterization of good responders to various anti-obesity drugs . The identification of response patterns to specific anti-obesity drugs can increase the efficacy of these drugs, which will be an initial step toward personalized medicine for obesity treatment. Orlistat & Tablets While GLP-1s have grabbed a lot of headlines, they are only the latest in a long history of evolving weight loss medications. Some weight management medications are designed for short-term use and others for long-term use. A treatment plan for obesity can comprise multiple forms of treatment, including medications, diet, exercise, and/or surgery. In a Phase 2 study, the medication showed up to 20% average weight loss at 52 weeks for people with obesity or overweight. If you're taking medicine for another serious health condition, such as type 2 diabetes, high blood pressure or kidney disease, it may be necessary to change the dose of your medicine. You'll need to start eating a balanced diet and exercising regularly before starting treatment with orlistat, and continue this during treatment and after you stop taking the medicine. Never take a medicine for weight management if it has not been prescribed for you. All medicines for supporting weight management should be used alongside a reduced-calorie diet and increased physical activity. Additionally, liraglutide has been shown to improve hepatic steatosis in patients with non-alcoholic steatohepatitis , and after a 26-week intervention, ovarian dysfunction, with 5.2 kg of weight loss, in overweight women with polycystic ovary syndrome . At week 32, the AHI was significantly lower, with weight loss, in the liraglutide group than in the placebo (−12.2±1.8 events h−1 vs. −6.1±2.0 events h−1) . The mean weight loss was significantly higher in the liraglutide group than in the placebo group (SCALE-Obesity and Prediabetes, 8.4 kg vs. 2.8 kg; SCALE-Diabetes, 6.4 kg vs. 2.2 kg; SCALE-Maintenance, additional 6.2% vs. 0.2%, respectively) 41–43. Yes, all medications are made in a State Board of Pharmacy licensed 503(A) compounding pharmacy, or 503(B) Outsourcing Facility. Please refer to your preferred treatment page for pricing options, or visit Programs - Henry Meds. With that in mind, Henry is designed for patients seeking long-term care. Always consult your healthcare provider regarding your specific health needs. All medications are prescribed only after an independent clinical assessment by a licensed provider. What to expect on medication 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. As with many medications, some weight loss drugs have been on the market longer, have generic alternatives, and tend to be more affordable. Even as the range of weight loss medications has expanded, some drugs have been withdrawn based on their lack of efficacy as well as safety concerns. In the OASIS 1 Phase 3 trial, the oral formulation achieved an average weight loss of 15.1%over 68 weeks compared to 2.4% with placebo. Some patients may lose 5–10% of body weight, especially with the higher dose of liraglutide. Some insurance plans cover weight loss medications, while others don’t. These medications are extremely effective tools for weight loss. Even certain medications and health conditions may cause weight gain. Before 2012, there were few weight loss medications approved by the FDA. The starting dose should be low (12.5–25 mg daily) for obesity management and the maximum dose should be 100 mg daily in two divided doses of 50 mg. It has not been approved by the Therapeutic Goods Administration for the treatment of obesity in Australia because no one has applied to register it for treating obesity. The genetic basis of obesity explains why the body defends weight so vigorously. A personalised approach must be used when selecting the appropriate weight loss drug for the patient. Amgen is developing MariTide, a monoclonal antibody designed to increase GLP-1 receptor activity while reducing GIP receptor activity. At this writing, it is in Phase 3 clinical trials. The first, orforglipron, is an oral GLP-1 inhibitor that completed a Phase 3 clinical trial in early 2025. Gorgojo-Martínez et al. found liraglutide to be more effective at weight loss as well as obesity-related metabolic and cardiovascular complications than orlistat . The combination of phentermine-topiramate allows minimal side effects with proven efficacy for weight loss. At the one-year point, excess weight loss compared to placebo was 8.8 kg (95% CrI-10.20 to -7.42 kg), while it was 2.6 kg with orlistat compared to placebo (95% CrI -3.04 to -2.16 kg) . The combination of phentermine with topiramate has been approved by FDA for the management of obesity. The addition of medications like orlistat, which are FDA-approved and has an established safety profile, is not only helpful for initial weight loss but also its maintenance. Tirzepatide works on 2 GLP receptors and is known to promote faster weight loss...although more expensive. These are estimates and we have found many patients to lose more weight. University of Utah Health experts help patients fix underlying issues contributing to obesity. Losing even a small amount of weight can have huge positive impact on your overall health. While it’s true that GLP-1 medications, like Ozempic and Wegovy, can make you lose weight, it’s not wise to run to your nearest pharmacy. The safety of liraglutide has not been demonstrated among those who are older than 75 years; thus, it is not recommended in this population . Peripherally, liraglutide delays gastric emptying after a meal and regulates the balance between insulin and glucagon secretion for glycemic control (Fig. 1) . Related symptoms should be observed carefully and the drug should be discontinued as soon as symptoms occur. What are the concerns about using prescription medications to lose weight? Zepbound is approved to treat obesity in adults with a BMI of 30 or greater.The most common side effects are gastrointestinal, such as nausea, constipation, or diarrhea, which are generally mild.Setmelanotide is also being evaluated for the treatment of PWS, Bardet–Biedl syndrome, Alstrӧm syndrome, POMC heterozygous deficiency obesity and POMC epigenetic disorders.81The possible superiority of semaglutide with a similar risk of adverse events makes it an excellent choice of drug for the management of obesity in the patient population willing to take subcutaneous medication .The study findings reinforced previous findings that phentermine/topiramate ER intake can result in meaningful weight loss and significant improvements in BP, lipid profiles, fasting glucose, fasting insulin, and WC.The expected weight loss required to improve obesity-related complications and mean weight loss according to treatment.The U.S. National Institutes of Health recommends anti-obesity drugs for individuals with BMI ≥30 or ≥27 kg/m2 with comorbidities, such as diabetes, hypertension, dyslipidemia, or sleep apnea . Obesity is a major public health threat, and obesity rates have been alarmingly increasing in the last few decades.1 The highest prevalence is reported in the Pacific Islands states, where obesity affects more than 50% of the population.2 In United States, individuals with obesity constitute almost one third of adults, with a prevalence ranging between 23% and 38% across various states.2 The worldwide situation has worsened recently following the COVID-19 pandemic.3,4 Large long-term trials are required to demonstrate the benefit of obesity pharmacotherapy on clinically relevant hard outcomes. We suggest a treatment algorithm taking into consideration patient's profile and medications efficacy and safety data. Although there are no RCTs that specifically examined the efficacy ofphentermine/topiramate in patients with obesity and hypertension, data from thesubset of patients with hypertension support its use in this patient population. Furthermore, approximately 8% ofpatients discontinued orlistat in clinical trials due to gastrointestinaladverse effects . The effects of lorcaserin, liraglutide 3.0 mg, and naltrexone/bupropionon blood pressure have not been specifically studied in RCTs among patients withobesity and hypertension. Among the pharmaceutical interventions currently approved for long-termweight management, the combination drug therapy of naltrexone/bupropion is theonly one that raises blood pressure. For all other drugs, the results are basedon pooled data of phase 3 RCTs in patients with obesity without diabetes asdrawn from the FDA advisory committee briefing documents . The BLOOM and BLOSSOM studies showed that of those in the active drug groups, approximately 35–48% participants had weight loss at or above 5% of their baseline body weights.28,29 The CAMELLIA-TIMI 61 study showed that over the course of 3 years, lorcaserin did not increase the occurrence of major cardiovascular events.27 Additionally, blood pressure, heart rate, low-density lipoprotein cholesterol, triglycerides and glycated hemoglobin (HbA1c) all showed improvement compared with placebo, and the mean percentage of diabetes onset decreased after 1 year of treatment.27 Although orlistat has advantages in terms of its ease of administration and tolerability, its potential for weight loss is less than that of other approved anti-obesity drugs. Moreover, the proportion of patients who lost 10% of their weight after 1 year of treatment is also different among phentermine/topiramate CR (54%), liraglutide (34%), naltrexone ER/bupropion ER (30%), and orlistat (20%) groups. Therefore, guidelines recommend that obese individuals lose 5% to 10% of their initial body weight within 6 months of starting a weight-loss intervention (Kim et al., 2023). Specifically, weight loss of 5% to 10%, along with improvements in lifestyle, has clinically significant benefits in achieving these goals. His commitment to obesity medicine comes from personal and family struggles with obesity, guiding his holistic approach that connects obesity to health issues, including mental health. Some patients have taken these alternatives, which are generally more affordable, without ill effects. Weight-positive medications in the tricyclic antidepressant category include amitriptyline, doxepin, and imipramine. This relationship can allow for dosage adjustments or alternative medications if one seems like a better fit for the patient. These programs apply only to self-pay patientsand are not covered by insurance. According to GoodRx, phentermine can be had for as little as $10. A patient who stops these may regain some or all of the weight. Phentermine by itself (Adipex-P, Lomaira) also is used for weight loss. They may switch you to a different weight-loss drug. How long you take a weight-loss drug depends on whether the drug helps you lose weight. But practicing healthy lifestyle habits may help limit weight gain. If you're overweight, losing even just 5 pounds (2.3 kilograms) can lower your blood pressure. Please consult a healthcare professional in the UK for advice tailored to your needs. Scott is an experienced, skilled medical content writer dedicated to creating helpful and accessible health and wellbeing content for UK Meds. See how real people are transforming their lives using treatments and lifestyle changes. However, they can have side effects (like nausea), which is why a medical consultation is required. Studies are currently underway to investigate semaglutide as an obesity treatment in both pediatric and adult populations. As a GLP-1 agonist already FDA approved to treat type 2 diabetes, it is following in its predecessors’ footsteps as it undergoes phase III trials to investigate its efficacy in treating obesity in adolescents. The most recent GLP-1 agonist to show promise in being an effective obesity treatment is semaglutide. A study investigating the safety, tolerability, and pharmacokinetics of liraglutide over a 5-week treatment period enrolled adolescent participants (12–17-years old) with obesity. To lose weight, you need to lower the total calories you take in from food and drinks. You set action goals so that you can make healthy changes. You can list a healthy outcome that you aim to have. Although many long-term trials demonstrated beneficial effects of lorcaserin in T2DM and its substantial CVD safety profiles, weight loss efficacy of lorcaserin is only modest. At the conclusion of the trial, a weight loss greater than 10% was achieved in 22.6% of participants in the lorcaserin group vs. 7.7% in the placebo group. Unlike other anti-obesity drugs on the market, orlistat does not exert its effect by affecting appetite; instead, it reduces calorie absorption. If you experience these symptoms, contact your healthcare provider right away. “With all four legs on the ground, you have a pretty stable base to lose weight,” Primack says. Progress in pharmacotherapy for obesity. New drug therapy approvals 2022. Two trials have investigated exenatide’s effect on weight loss in children and adolescents. It has been noted in rodent studies that liraglutide can cause calcitonin levels to increase.42 Liraglutide can be considered even if patients have a history or diagnosis of mental health disorders.56 Obesity treatment using liraglutide starts at 0.6 mg, and the dose is titrated to the targeted dose of 3 mg. Transform your health + well-being Bupropion (BUP) is a dopamine and norepinephrine reuptake inhibitor known for its role in the management of depression and smoking cessation.Most importantly, always discuss over-the-counter drugs or supplements with your health care provider.In the SCALE-Sleep Apnea trial, 180 non-diabetic patients with obesity who had moderate or severe obstructive sleep apnea (OSA) were randomized to liraglutide 3.0 mg or the placebo group to examine whether liraglutide reduces the severity of OSA using the primary endpoint of the change in the apneahypopnea index (AHI) after 32 weeks.If you prefer to keep your weight-loss efforts private, take some steps to stay on course.This approval followed that of a lower dose (1.8 mg daily Victoza®) in 2010 for T2DM management .It's nearly impossible to maintain weight loss without it.Some patients who are less comfortable with injections may ask about weight-loss pills.Specialist programs (eg a Healthy APproach to weIght management and Food in Eating Disorders HAPIFED in Australia)12 combine evidence-based psychological therapy for eating disorders with behavioural weight loss interventions. "That said, consumers could also eat more weight management foods as they strive to eat healthier and substitute such products over more indulgent snacking alternatives," he added. "Greater adoption of GLP-1 drugs could be thought of as a substitute for categories of food products that are more attuned to health and wellness," analyst Andrew Lazar said in a research note last year. Whether weight loss meds will leave consumers more or less likely to reach for healthy products is not yet certain, however, according to Barclays analysts. "If you go to weight loss and you're successful, you move to the health, nutrition, lifestyle counter, because you basically want to continue what you have. There we come into play," de Vreeze told CNBC's "Squawk Box Europe." Please refer to your preferred treatment page for pricing options, or visit Programs - Henry Meds.Supplementation with multivitamins is recommended to compensate for the potential malabsorption of fat-soluble vitamins with orlistat therapy (Jeon et al., 2023).At 68 weeks, the STEP 1 trial reported mean SBP and DBP reductions of 6.2 mmHg and 2.8 mmHg respectively in the intervention group, compared to 1.1 mmHg and 0.4 mmHg respectively in the placebo group (p 82 In STEP 4-Maintenance trial reported mean SBP and DBP elevations of 0.5 (13.0) mmHg and 0.3 (8.8) mmHg respectively in the intervention group, compared to 4.4 (13.0) mmHg and 0.9 (10.5) mmHg, respectively, in the placebo group (p 83 STEP 3-IBT trial resulted in reductions in SBP and DBP of 5.6 mmHg and 3.0 mmHg, respectively, for participants receiving semaglutide 2.4 mg, compared to 1.6 mmHg and 0.8 mmHg, respectively, for those receiving placebo at 68 weeks (p 0.001 for SBP; p 0.008 for DBP) (Table 2).84Health care professionals use the Body Mass Index (BMI), a measure of your weight in relation to your height, to define overweight and obesity.Many people regain most of the weight within 2 years after they stop using it.But not everyone loses weight while taking them.Moreover, as there is growing evidence that these drugs can delay the onset of obesity-related complications and improve metabolic and cardiovascular parameters, they should be considered in a timely manner. Weight-loss drugs aren't an easy answer to weight loss. It's one of four similar weight-loss drugs approved for use for less than 12 weeks, called short-term use. Phentermine-topiramate is a combination of a weight-loss drug called phentermine and an anticonvulsant called topiramate. The FDA recommends that if a weight reduction of less than 3% is achieved after 12 weeks of use, the drug should be either discontinued or the dose increased. In the secondary endpoint analysis of all clinical trials, the phentermine/topiramate CR group showed significant improvements in cardiometabolic risk factors, including waist circumference, glycemic control, and lipid profile 37,38. A similar result was obtained for patients who achieved ≥10% weight loss (7% vs. 37% vs. 48%) . The Controlled-Release Phentermine plus Topiramate Combination in Overweight and Obese Adults (CONQUER) study was conducted among 2,487 overweight and obese patients with a BMI of 27 to 45 kg/m2 and two or more cardiometabolic diseases, such as hypertension, dyslipidemia, prediabetes or diabetes, and abdominal obesity. The change in triglycerides differed between arms, with a ratio of change over baseline of 0.78 for patients taking semaglutide compared to a ratio of 0.93 in patients on placebo (Table 2).82 The STEP 4 maintenance trial reported mean percent changes in lipid parameters at 68 weeks of treatment. However, several trials investigated the efficacy of orlistat, alone or in combination with Metformin or insulin treatment, in patients with overweight or obesity and DM with suboptimal control. The aim of this manuscript is to review the pharmacologic management of obesity in adults, suggest an algorithm for the treatment approach of excess weight, and describe potential drugs that are currently under investigation. Most people will regain some or all of the weight after they stop taking the medicines, unless they have made lasting lifestyle changes. But not everyone loses weight while taking them. Several weight-loss medicines are available in the United States. The starting dose is one tablet (bupropion 90 mg/naltrexone 8 mg) daily, gradually increasing to two tablets twice daily. Low doses work very well in a subset of the population, but higher doses are needed by some. Although GLP-1 agonists lower glucose in patients with diabetes, they do not cause hypoglycaemia in individuals who do not have diabetes. The dose can be slowly increased up to 3 mg daily, if required. It requires a daily injection with a starting dose of 0.6 mg. Once-daily dosing in comparison to weekly dosing of semaglutide also creates comparatively more inconvenience. More studies need to be performed to further assess the long-term safety and benefits related to cardiovascular and metabolic health. However, due to the scarcity of information on long-term side effects, a longer prospective observational study would likely help address some of those concerns. The studies have been able to establish the efficacy, but data is lacking regarding long-term side effects. It is an oral medication that most commonly causes gastrointestinal adverse effects, including steatorrhea due to impaired fat absorption, which may lead to a deficiency of fat-soluble vitamins and nutrients . In the 4-year XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) trial, the orlistat group achieved a 6.9% reduction in body weight compared with a 4.1% reduction in the placebo group at the end of the study.It should be taken as directed by your health care provider.Meanwhile, a significant decrease in the absorption of vitamins A, D, E, and K was observed in participants administered orlistat .You may lose about 25% of your muscle mass as you lose weight.The reported adverse reactions related to setmelanotide treatment are injection site reactions, nausea, vomiting, and hyperpigmentation.Even this amount of weight loss can lower your risk of some long-term health conditions.Despite the high efficacy of GLP-1-based anti-obesity medications, the need for regular injections is still a significant barrier for many patients.In the STEP 3 trial LDL-C level dropped with semaglutide by 4.7%, while it increased by 2.6% with placebo (p Table 2).84 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. There was no difference in liver stiffness, the primary outcome, measured using magnetic resonance elastography.103 Conversely, the proportion of participants who had at least 30% reduction in liver steatosis in the semaglutide group was almost 2-fold the proportion in the placebo group, 73% and 33%, respectively at 72 weeks (p 0.0006).103 Total body weight loss was higher with semaglutide, with an estimated difference of −9.6% (p ≤ 0.0001), compared to placebo, and whether total body weight loss was the driver of the benefit on liver steatosis was not explored. A post-hoc analysis of the COR trials showed a significant improvement in liver enzymes in the NB group compared to placebo; this effect was directly driven by total body weight loss. Conversely, there was a trend for an increase in SBP and DBP, in the placebo groups (p 64 At 56 weeks, CONQUER trial reported mean SBP and DBP reductions of 4.7 (13.6) mmHg and 3.4 (9.2) mmHg respectively for the low dose phentermine/topiramate, 5.6 (15.1) mmHg and 3.8 (9.8) mmHg respectively for the high dose phentermine/topiramate, and 2.4 (14.5) mmHg and 2.7 (9.8) mmHg for the placebo group (p 65 The decrease in BP seen in the EQUIP trial was relatively small compared to the changes reported in the CONQUER trial. In fact, the EQUIP trial enrolled normotensive participants while the CONQUER trial recruited a population with hypertension and other cardio-metabolic disorders. At 52 weeks, SEQUEL, the extension of CONQUER trial reported similar changes in SBP and DBP (Table 2).66 That's part of the reason why there's little scientific proof to show that weight-loss supplements work. You might be surprised to learn that makers of dietary supplements rarely do clinical trials. Stores sell dietary supplements as health aids. “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. “A long time ago you only saw thin people in magazines and on television before the movement that emphasizes body positivity. Here’s what to know about how weight loss medications work, who they’re best for, potential side effects, and more. FDA approves treatment for chronic weight management in pediatric patients aged 12 years and older. FDA approves weight management drug for patients aged 12 and older. VCU researcher partners with T-Mobile to expand VR mental health therapy for youths First, not every drug will produce effective results in patients and individual responses will vary widely. Patient preferences based on tolerability markedly affect adherence and can cause poor adherence or discontinuation, thereby negating the treatment effects 13,14. Weight loss is extremely challenging to achieve and sustain, and long-term management of obesity often requires adjunctive pharmacological interventions. Interestingly, these drugs are effective, to some extent, in individuals without diabetes . As obesity occurs via multifactorial pathways, a single drug might exhibit limited efficacy. Naltrexone (NAL) is an opioid receptor antagonist approved as a treatment for opioid dependency and alcohol dependence.One clinical trial reported 1.3% weight loss in the placebo group and 6.1% weight loss after NAL/BUP administration at a dose of 32 mg for 56 weeks.Just as obesity is a multi-faceted disease, future treatment for adolescents with obesity could be accomplished through multiple modalities including the use of multiple medications.Prescription medications to treat overweight & obesity.Daily doses with four strengths start at 3.75 mg/23 mg to 15 mg/92 mg.The body mass index or BMI predates the bathroom scale by more than half a century, but it has not changed with the times.For recommended treatments, please consult with your health care provider. In EQUIP, the reported reductions in SBP and DBP, at 56 weeks, were of a small magnitude, for both low dose and high dose groups. At 1-year, systolic (SBP) and diastolic blood pressure (DBP) dropped by 7.3 mmHg and 3.6 mmHg respectively, for the intervention group, and 5.2 mmHg and 2.6 mmHg, respectively for the placebo group (p Table 2).58 LDL-C level was similar between both arms, with ratios of 0.97 and 1.01 for the intervention compared to control, respectively. Across all STEP trials, there was no significant difference in the HDL level between arms after the intervention.82, 83, 84 The STEP 1 trial reported the ratio of measurement at 68 weeks over baseline for all lipid parameters. The SCALE Obesity and Prediabetes reported mean change in lipid parameters at 56 weeks of treatment. At the end of the trial, a greater weight loss effect was observed in the treatment groups than in the placebo group (−1.4 kg vs. −8.1 kg vs. −10.2 kg) and the proportion of patients who achieved ≥5% weight loss was significantly higher in the treatment groups than in the placebo group (21% vs. 62% vs. 70%) at week 56. 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%). From this perspective, in this review, we discuss obesity treatment strategies, focusing on pharmacological approaches with anti-obesity drugs approved for long-term use in patients with obesity. One of the main challenges in weight management is the inability to predict patient's response to medications, with a wide variability in individuals weight change in response to a given medication.239 With the exception of semaglutide trials where the majority of participants had a significant weight loss, in the AOM trials, 20–50% of participants lost 240,241 Such approach requires the availability of large cohorts to collect data on genetics, epigenetics, and genomics, and therefore derive a therapeutic algorithm.241 The OBEsity Diverse Interventions Sharing (OBEDIS) – focusing on dietary and other interventions - aims at streamlining and harmonizing variables and endpoints of AOM clinical trials, to allow data pooling and derivation of prediction models.242 Furthermore, whether this effect has been driven solely by total body weight loss, rather than a direct effect of the drug per se, and whether it differs between metabolically healthy and metabolically unhealthy individuals with obesity, has been poorly investigated.234 While some available data showed improvement in liver steatosis with GLP1-RA, there is no evidence of reduction in liver fibrosis with any AOM, a parameter that requires longer term studies to show benefit. You should take a daily multivitamin if you use orlistat. You can also buy orlistat without a prescription under the name Alli. Xenical is the brand of orlistat your provider can prescribe for you. The most unpleasant side effect of orlistat is oily diarrhea that may leak from the anus. As a chronic and relapsing disease, obesity negatively impacts the health of men to a greater extent than that of women, with a higher risk of cardiovascular disease. “I think it is a very exciting time for obesity medicine because we now have several effective treatments to choose from,” says Melanie Jay, MD, an obesity researcher and a professor at the New York University Grossman School of Medicine in New York City. If you have diabetes that needs treatment with medicines, you may want to ask your provider about diabetes medicines that often lead to weight-loss. Be sure you understand the side effects of weight-loss medicines. Your body may not absorb important vitamins, minerals, and other nutrients from food while you are using orlistat. Lifestyle modifications with and without weight loss in hypertension Tirzepatide is a dual GIP and GLP-1 receptor agonist that suppresses appetite, improves satiety, and supports metabolic health. With more options available, doctors will be increasingly able to personalize treatments. Researchers continue to study hormones that play a role in appetite for other ways to target obesity with medication. The once-monthly injection entered Phase 3 clinical trials in March 2025. Based on the benefits of dual GLP-1/GIP RAs and dual GLP-1/glucagon RAs, the effect of triple GLP-1/GIP/glucagon RAs on weight loss and glycemic control has also been investigated. The end-of-treatment heart rate increase was similar to or slightly higher than that observed with placebo (Ji et al., 2023). However, heart rate tended to increase more with mazdutide than with placebo (Ji et al., 2023), similar to the phase 1 trial (Ji et al., 2021, 2022). Based on this concept, Cegla et al. investigated the acute effects of intravenous infusion of a subanorectic dose of GLP-1 and glucagon on food intake. Can men and women use the same medications? What side effects should I expect? Can I use these medications if I have diabetes? At the one-year point, excess weight loss with orlistat compared to placebo was 2.6 kg (95% CrI -3.04 to -2.16 kg) . “These medications help people lose weight and help them keep it off.” The drugs have many positive effects, everything from a reduced appetite to benefits to the heart, kidneys and liver. The U.S. Food and Drug Administration (FDA) has approved a few prescription drugs for long-term weight loss use. “We now have a generation of very effective weight loss drugs,” says Craig Primack, MD, an obesity medicine physician with Scottsdale Weight Loss Center in Scottsdale, Arizona. Exenatide, a GLP1-RA, was explored in the treatment of patients with obesity, without DM. Anti-obesity medicationsa in the horizon identified from Clinicaltrials.gov. After starting AOM, responders are those who lose at least 5% of their baseline weight after 3 months of therapy and should continue their treatment.10 Conversely, those who don't achieve this target are considered as non-responders and should be switched to another drug.10 The suggestion for the use of Liragluide and Semaglutide in patients with obesity and DM is based on the fact that GLP-1 receptor agonists are anti-diabetic medications. Suggested algorithm for the selection of anti-obesity medications, taking into consideration the availability of drug safety, contra-indications, and preliminary efficacy data for a specific patient profile.a CVD, cardiovascular disease; DM, diabetes mellitus; HTN, hypertension; MTC, medullary thyroid cancer; NAFLD, non-alcoholic fatty liver disease. In most clinical trials that evaluated pharmacologic interventions for more than 12 months, a weight loss of 4% to 8% was typical ; however, this is rather disappointing considering the high prices of these drugs. To date, however, there has been no approved combination agent for obesity management, besides phentermine/topiramate and naltrexone/bupropion. One of the main benefits of liraglutide, besides weight loss, is its favorable effects on CVD outcomes in obese patients with T2DM. The proportion of patients with weight loss of at least 5% is 3.4, 2.3, and 1.7 times higher for phentermine/topiramate CR than for orlistat, naltrexone ER/bupropion ER, and liraglutide, respectively. A network meta-analysis that studied differences in the efficacy of anti-obesity drugs showed that phentermine/topiramate CR has the greatest weight loss effect among the currently used anti-obesity drugs . For phentermine/topiramate, NB and liraglutide, the FDA includes “Suicidal Behavior and Ideation” under “Warning and Precautions” and recommends to monitor patients for depression and suicidal thoughts, and to stop the drug in case of symptoms development.68,74,81 Data on orlistat and semaglutide in patients with mental diseases is still lacking. In a phase 2 trial, 320 patients with biopsy proven non-alcoholic steatohepatitis (NASH), using the definition of the NASH Clinical Research Network, were randomized to receive semaglutide (0.1, 0.2 or 0.4 mg daily) or placebo.104 Histologic findings at 72 weeks showed that the proportion of NASH resolution was higher in semaglutide groups, and the highest proportion 59% reported in the 0.4 mg semaglutide group and only 17% of the placebo group (p 104 However, there was no difference in the fibrosis parameters between groups.104 Whether total body weight loss, rather than the intervention per se, is responsible of the beneficial impact of NASH still needs further investigation.104 Use of antidepressant drug Those not gaining weight spontaneously increased their daily energy expenditure by around 2000 kilojoules.3,4 Forced overfeeding studies from America have shown that, despite a group of individuals being overfed by the same amount, there is a range of weight gain. There is strong evidence that obesity has a predominantly genetic1 or epigenetic2 basis. However, topiramate in combination with phentermine was approved for the treatment of obesity by the FDA in 2012. Compared to switching to placebo after 20 weeks, continued treatment with semaglutide can sustain weight loss.7 Several drugs do not have an approved indication in Australia for weight loss. Like all drugs, these diabetes and weight loss drugs have side effects and contraindications. After 56 weeks, a weight loss of 8.0% was achieved in the liraglutide group (vs. 2.6% of placebo) and 63.2% and 33.1% of the participants in the liraglutide group achieved ≥5% and ≥10% weight reduction, respectively (vs. 27.1% and 10.6% in the placebo group, respectively). Liraglutide (Saxenda®) is an injectable glucagon-like peptide 1 (GLP-1) derivative that was approved by the FDA in 2014 for weight management (dose, 3.0 mg subcutaneous SC daily). The final study, the COR-DM trial, evaluated weight loss in 505 patients with T2DM who were either overweight or obese . Naltrexone was approved for the treatment of opioid and alcohol addiction and antagonizes an opioid-dependent feedback loop that limits the effects of bupropion on the POMC neurons; hence, this drug combination works synergistically . These treatments work best when combined with nutrition, exercise, and behavioural support. These medications typically work by either regulating appetite, slowing digestion, or blocking fat absorption. Struggling to lose weight despite lifestyle changes? The American College of Cardiology (ACC) is a global leader dedicated to transforming cardiovascular care and improving heart health for all. Glabridin analogue HSG4112 regulates metabolic gene expression by increasing energy expenditure in the liver and muscles200 and is being studied in a phase 2 trial.201 If prescribed, subscription includes unlimited access to healthcare providers, medication, applicable supplies, and shipping. Free evaluations offered for many of our treatments. The cardiovascular safety of naltrexone ER/bupropion ER is not yet known, as the only relevant cardiovascular outcome trial was unblinded early. In the COR-I trial, HDL-C increased significantly in intervention arms compared to placebo (p Table 2).70 The changes in the COR-II trial followed the same pattern (Table 2).71 The changes in the intervention arms were significantly different than the placebo arm for HDL-C, LDL-C and triglycerides levels (Table 2).65 The changes in lipid level reported in the SEQUEL trial were very close to those in the CONQUER trial, and there was a trend for a dose dependent increase in HDL and decrease in TG (Table 2).66 The CONQUER trial showed similar, though larger, effects on lipid parameters after 56 weeks of treatment, possibly due to the addition of lifestyle modifications to all participants. After 1 year of treatment, patients taking Orlistat showed an increase in High-density lipoprotein cholesterol (HDL-C) and a decrease in Low-density lipoprotein cholesterol (LDL-C); changes of a small magnitude but significantly different than placebo (p Table 2).58 A similar pattern was seen at the 4-year mark in both HDL and LDL, while there was no difference in triglycerides level between arms (Table 2).58 These medicines work in the kidneys where they help take extra sugar out of the blood that then goes out of the body in urine. More common side effects often improve after taking the medicine for a while. As with any medicine, there is a risk of side effects when taking a GLP-1 agonist. For much of 2023 and 2024, these drugs have been plagued by shortages in the marketplace. When we overeat, that’s when the nausea comes in.” She added that there are some patients who find the side effects intolerable, but “they are very few and far between.” Since all the drugs are relatively new, there are no generic versions available yet. “The drugs are the same, except the FDA approval and the labeling and marketing are different,” Norinskiy says. The combination of naltrexone, an opioid receptor antagonist, and bupropion, a norepinephrine-dopamine reuptake inhibitor, is used for the management of obesity . The side effects that resulted in discontinuation of treatment included blurry vision, headaches, insomnia, paresthesia, irritability, dizziness, anxiety, and depression . Orlistat has been shown to be effective for achieving weight loss of 5% or more from baseline. Orlistat is a pancreatic lipase and gastric lipase inhibitor that can lead to a decrease in fat absorption by as much as 30% contributing to weight loss 12,13. Clinically significant weight loss is defined as at least a 5% reduction of weight from baseline over a period of three months .