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The rising prevalence of obesity is of major concern. There are currently 5 Food and Drug Administration-approved medications for the treatment of obesity: orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide 3.0 mg, and semaglutide 2.4 mg. Surgical options such as bariatric surgery and endoscopic surgery induce more durable weight loss than pharmacotherapy or lifestyle interventions alone. However, patients often experience weight regain and weight loss plateau after surgery. The addition of multimodal or multihormonal pharmacotherapy is a promising tool to address these challenges. The optimal timing of obesity pharmacotherapy with surgical and endoscopic interventions requires further investigation., Competing Interests: Disclosure J.O. Alemán is a consultant for Novo Nordisk and clinical advisory board member for Intellihealth. The authors declare that they have no relevant or material financial interests that relate to the data described in this study. Funding Doris Duke Charitable Foundation (JOA), American Heart Association 17- SFRN33490004 (JOA), NIH K08 DK117064 (JOA), NIH NHLBI P01 HL 160470-01A1 (JOA)., (Published by Elsevier Inc.)

Background: Obesity is a complex disease for which pharmacotherapy is often used. Anti-obesity drugs (AODs) are characterized by inducing a variable inter-subject body weight reduction (BWR), the attainment of a plateau after their maximal effect is achieved, and weight regain after drug discontinuation, which complicate individualized treatment of obesity., Objective: This exploratory analysis aimed to compare the first-month body weight reduction in kg (1mo-BWRkg) and tolerance development (moT) of four known interventions with low (placebo), intermediate (phentermine or mazindol monotherapy), and high (5 active ingredients fixed-dose combination) efficacy, as predictors of their 6-month body weight reduction efficacy in percent (6mo-BWR%). In addition, a detailed analysis of the 6-to-12-month BWR follow-up in subjects under orlistat or diet and exercise regimens was performed., Materials and Methods: The analysis included 662 adult subjects with obesity. After the construction of average efficacy and weight rebound curves, subjects were grouped into various 1mo-BWRkg, moT, and 6mo-BWR% intervals, or 6-month body weight rebound parameters for further evaluation., Results: The 6mo-BWR% efficacy level of interventions was confirmed, although a general high intersubject variation was observed. 1mo-BWRkg + moT was found as an acceptable predictor of 6mo-BWR%. Between 50 and 80% of the 6-to-12-month follow-up completers maintained at least 5% BWR%., Conclusion: Short-term AODs are useful adjuvants for the 1-year rational treatment of obesity. 1mo-BWRkg + moT is an acceptable parameter to predict the 6mo-BWR% efficacy of these interventions.

Importance: Obesity affects approximately 19% of women and 14% of men worldwide and is associated with increased morbidity. Antiobesity medications (AOMs) modify biological processes that affect appetite and significantly improve outcomes, such as type 2 diabetes, hypertension, and dyslipidemia., Observations: AOMs should be administered in combination with lifestyle interventions and can be classified according to their mechanisms of action. Orlistat modifies digestive tract absorption and causes gastrointestinal adverse effects, such as oily fecal spotting and urgency, in more than 25% of patients. Centrally acting drugs, such as phentermine-topiramate and naltrexone-bupropion, regulate appetite in the brain and are associated with constipation in approximately 20% of patients, although the incidence of other adverse effects (eg, paresthesia, nausea) varies by medication. Nutrient-stimulated hormone-based medications, such as liraglutide, semaglutide, and tirzepatide, mimic the actions of enteropancreatic hormones that modify central appetite regulation and provide multiple cardiometabolic weight-loss benefits. Adverse effects of these drugs include nausea (28%-44%), diarrhea (21%-30%), and constipation (11%-24%). The relative potency of adult obesity medications has been studied in meta-analyses. Compared with placebo, orlistat was associated with 3.1% greater weight loss (52 randomized clinical trials [RCTs]; 16 964 participants), phentermine-topiramate was associated with 8.0% greater weight loss (5 RCTs; 3407 participants), naltrexone-bupropion was associated with 4.1% greater weight loss (6 RCTs; 9949 participants), liraglutide was associated with 4.7% greater weight loss (18 RCTs; 6321 participants), semaglutide was associated with 11.4% greater weight loss (5 RCTs; 4421 participants), and tirzepatide 15 mg was associated with 12.4% greater weight loss (6 RCTs; 1972 participants)., Conclusion and Relevance: Obesity is associated with increased morbidity. Antiobesity medications are effective adjunctive therapy to lifestyle changes for improved weight loss and health outcomes.

Background: Anti-obesity medications (AOMs) are promising lifestyle modification (LSM) adjuncts for obesity treatment, and phentermine is commonly prescribed in paediatric weight management clinics. Determining 'real-world' AOM effectiveness and characteristics predicting response is important., Objectives: We sought to describe phentermine plus LSM effectiveness and identify baseline characteristics predicting response., Methods: This was a retrospective cohort study among youth seen in a US academic-based weight management clinic from 2012 to 2020. Baseline characteristics (e.g., body mass index (BMI), liver transaminases, eating-related behaviours) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, %BMI change, weight) were determined through electronic health records and intake surveys., Results: Among 91 youth prescribed phentermine plus LSM over 8 years (mean %BMIp95 150%), %BMIp95 was statistically significantly reduced at 1.5, 3, 6 and 12 months (peak reduction 10.9 percentage points at 6 months; p < 0.001). Considering multiple comparisons, the presence of baseline elevated alanine aminotransferase was associated with statistically significant smaller 1.5-month %BMIp95 reductions (p = 0.001) and higher food responsiveness with smaller 3- (p = 0.001) and 6-month (p < 0.001) reductions., Conclusions: Phentermine plus LSM reduced %BMIp95 among youth in a weight management clinic, and baseline characteristics may help determine those more or less likely to respond. Prospective studies are needed to further characterize effectiveness and confirm response predictors., (© 2024 The Author(s). Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Purpose: The aim of this study was to systematically analyze the prescription trends of medical narcotic appetite suppressants in South Korea., Materials and Methods: Data was extracted from the Narcotics Information Management System dataset from 2020, which encompasses nationwide information concerning the use of medical narcotics. The selected variables for this study included the types of prescribed medical narcotic appetite suppressants, gender, age, region, and the category of medical institution. Regional prescription trends were compared by utilizing the defined daily doses for statistical purposes (S-DDD)., Results: The prescription of medical narcotic appetite suppressants was predominantly for females (94%), with the highest prescription rates identified in the 30-40 age group. The majority of these prescriptions were dispensed by clinics. Within the category of narcotic appetite suppressants, phentermine and phendimetrazine were found to have higher prescription rates. Notably, the region of Daegu recorded the highest S-DDD value (12.66) in phentermine consumption., Conclusion: Our findings underscore the need for governmental policy and guidance to address the risks linked to the long-term use of medical narcotic appetite suppressants. This is crucial to ensure their safe and efficacious prescription and administration., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Obesity is a complex chronic disease and requires a long-term multidisciplinary management. Even patients undergoing bariatric surgery, one the most effective treatments for obesity, can have insufficient weight loss (IWL) than expected (primary non responder) or weight regain (WR) after a successful primary procedure (secondary non responder). A poor response represents a challenge of bariatric surgery that can induce persistence or recurrence of obesity-related comorbidities, prejudicing benefits of surgery. Increasing evidence suggests that weight loss medications represent a useful strategy in obesity care also after bariatric surgery procedures. This narrative review summarizes the evidence concerning anti-obesity therapy in the management of no-responders to primary bariatric surgery. Available data on liraglutide (one randomized double-blind placebo-controlled trial, three prospective and three retrospective studies), naltrexone/bupropion (three retrospective studies), orlistat (one case control prospective and one retrospective studies) and topiramate and phentermine (five retrospective studies) have been considered. Available data suggest that weight loss medications could offer a significant adjunctive benefit to lifestyle and behavioral modifications in the life-long management of obesity. Newer treatment modalities including the use of anti-obesity drugs provide patients and healthcare providers with more options in the management of poor response after bariatric surgery.

Purpose: A significant proportion of patients experience insufficient weight loss or weight regain after bariatric surgery. There is a paucity of literature describing anti-obesity medication (AOM) use following bariatric surgery. We sought to identify prevalence and trends of AOM use following bariatric surgery., Materials and Methods: We utilized the IBM Explorys® database to identify all adults with prior bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy). Those prescribed AOMs (semaglutide, liraglutide, topiramate, phentermine/topiramate, naltrexone/bupropion, orlistat) within 5 years of surgery were further identified. Data was analyzed to characterize AOM utilization among different age, demographic, and comorbid populations., Results: A total of 59,160 adults with prior bariatric surgery were included. Among AOMs studies, prevalence of use was highest for topiramate (8%), followed by liraglutide (2.9%), phentermine/topiramate (1.03%), naltrexone/bupropion (0.95%) semaglutide (0.52%), and orlistat (0.17%). Age distribution varied, with the highest utilization among those age 35-39 years for topiramate, 40-44 years for phentermine/topiramate and naltrexone/bupropion, 45-49 years for semaglutide, and 65-69 years for liraglutide and orlistat. African American race was associated with higher utilization across all AOMs. Among comorbidities, hypertension, hyperlipidemia, and diabetes mellitus were most associated with AOM use., Conclusion: Despite a relatively high incidence of weight regain, AOMs are underutilized following bariatric surgery. It is imperative that barriers to their use be addressed and that AOMs be considered earlier and more frequently in patients with insufficient weight loss or weight regain after bariatric surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The prevalence of obesity with various complications is increasing rapidly in Korea. Although lifestyle modification is fundamental in obesity treatment, more effective treatment tools are required. Many advances in obesity treatment have been reported recently, including lifestyle modifications and pharmacological, endoscopic, and surgical treatments. Drugs with proven long-term efficacy and safety are preferred because management for obesity treatment is a long-term process. Currently, four medications are available for long-term use in Korea: Orlistat, Naltrexone/bupuropion NR, Phentermine/topiramate capsule, and Liraglutide. Recently, semaglutide and tirzepatide have been attracting attention because of their effectiveness and convenience, but they are not yet available in Korea. In addition, there are limitations such as the yo-yo effect when discontinuing the drug, long-term safety, and cost. Patients and medical staff must be aware of the advantages and side effects of each medication to ensure the successful treatment of obesity.

Background: Severe obesity is a complex, chronic disease affecting nearly 9% of adolescents in the U.S. Although the current mainstay of treatment is lifestyle therapy, pediatric clinical practice guidelines recommend the addition of adjunct anti-obesity medication (AOM), such as phentermine and topiramate. However, guidance regarding when adjunct AOM should be started and how AOM should be used is unclear. Furthermore, an inherent limitation of current treatment guidelines is their "one-size-fits-all" approach, which does not account for the heterogeneous nature of obesity and high degree of patient variability in response to all interventions., Methods: This paper describes the study design and methods of a sequential multiple assignment randomized trial (SMART), "SMART Use of Medications for the Treatment of Adolescent Severe Obesity." The trial will examine 1) when to start AOM (specifically phentermine) in adolescents who are not responding to lifestyle therapy and 2) how to modify AOM when there is a sub-optimal response to the initial pharmacological intervention (specifically, for phentermine non-responders, is it better to add topiramate to phentermine or switch to topiramate monotherapy). Critically, participant characteristics that may differentially affect response to treatment will be assessed and evaluated as potential moderators of intervention efficacy., Conclusion: Data from this study will be used to inform the development of an adaptive intervention for the treatment of adolescent severe obesity that includes empirically-derived decision rules regarding when and how to use AOM. Future research will test this adaptive intervention against standard "one-size-fits-all" treatments., Competing Interests: Declaration of competing interest These authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: ACG, MS, DMV, NES, CTB, NJ. These authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: CKF receives research support from Novo Nordisk and Eli Lilly for serving as a site principal investigator. Compensation is paid directly to her institution. SJR receives research support from Novo Nordisk for serving as a site co-investigator. Compensation is paid directly to her institution. EMB is a site principal investigator and site co-investigator for Novo Nordisk. JRR receives donation of drug and placebo for a clinical trial from Boehringer Ingelheim. MOB receives research support in the form of donated study drug from Vivus Inc. ASK engages in unpaid consulting and educational activities for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Vivus; receives donated study product from Novo Nordisk and Vivus for National Institute of Diabetes and Digestive and Kidney Diseases-funded clinical trials. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Obesity is a chronic lifestyle issue with devastating results. Behavioral changes are one of the initial lines of management strategies for obesity, but they are not very efficient management strategies. Many people also use surgical intervention to maintain a healthy weight, now considered to be the most common and effective obesity management. Chemically synthesized medicines fill the gap between lifestyle interventions and minimally invasive surgical management of obesity. The most common issue associated with monotherapy without side effects is its moderate effectiveness and higher dose requirement. Combination therapy is already used for many serious and complicated disease treatments and management and has shown efficacy as well. Generally, we use two or more medicines with different mechanisms of action for a better effect. The commonly used combination therapy for obesity management includes low-dose phentermine and prolonged and slow-releasing mechanism topiramate; naltrexone, and bupropion. Phentermine with inhibitors of Na-glucose cotransporter-2 or glucagon-like peptide-1 (GLP-1) agonists with gastric hormone or Na-glucose cotransporter-2 are two more viable combo therapy. This combination strategy aims to achieve success in bariatric surgery and the scientific community is working in this direction., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Importance: Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown., Objective: To quantify cost-effectiveness of different antiobesity drugs available for pediatric use., Design, Setting, and Participants: This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature., Intervention: Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis., Main Outcomes and Measures: Incremental cost-effectiveness ratio., Results: Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93 620 per QALY relative to no treatment in this simulated cohort of 10 000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1 079 480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100 000 to $150 000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100 000 to $150 000/QALY., Conclusions and Relevance: In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100 000 to $150 000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.

Introduction: Management of patients with BMI≥50 kg/m 2 is challenging. In previous work, pre and postoperative pharmacotherapy with phentermine/topiramate plus laparoscopic sleeve gastrectomy (PT + SG) promoted greater weight loss than sleeve gastrectomy (SG) alone at 24 mo postoperatively. This current secondary analysis studied the impact of PT + SG on blood pressure (BP), heart rate, and antihypertensive usage., Methods: Patients with BMI≥50 kg/m 2 planning to have SG (n = 13) were recruited from 2014 to 2016, at an academic medical center in Winston-Salem, North Carolina, for this open-label trial. Participants took phentermine/topiramate (PT; 7.5/46-15/92 mg/d) for ≥3 mo preoperatively and 24 mo postoperatively. The control group (n = 40) underwent SG during the same time frame. We used mixed models for BP and heart rate to compare PT + SG versus SG alone over time, adjusted for age, sex, and initial BP., Results: By 24 mo postoperatively the model adjusted changes in systolic blood pressure/diastolic blood pressure (SBP/DBP) (mm Hg) were -24.44 (-34.46,-14.43)/-28.60 (-40.74,-16.46) in the PT + SG group versus -11.81 (-17.58,-6.05)/-13.89 (-21.32,-6.46) in the control group (SBP P = 0.02; DBP P = 0.03). At baseline 8 (61.5%) participants in the PT + SG arm and 22 (55.0%) in the control group used antihypertensives. Excluding patients lost to follow-up (n = 3), by 24 mo postoperatively, none of the PT + SG participants were on antihypertensives compared to 14 (41.2%) in the control group (P = 0.01)., Conclusions: Patients with BMI≥50 kg/m 2 treated with PT + SG had greater improvement in BP with no use of antihypertensive medication at 24 mo postoperatively versus SG alone, where 41% continued medication use. Larger trials are required to evaluate this., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Novel antiobesity treatments are highly effective in recent clinical trials. Access to these medications is needed to supplement lifestyle and surgical interventions for millions living with obesity worldwide, but high prices are limiting. This study aimed to review current treatment costs and calculate potential estimated minimum prices (EMPs)., Methods: The authors searched national drug price databases across various countries for orlistat, naltrexone-bupropion, topiramate-phentermine, liraglutide, semaglutide, and tirzepatide. EMPs for antiobesity medications were calculated using established methodology, using active pharmaceutical ingredients (API) from the Panjiva database. EMPs were calculated per 30-day course and include costs of active pharmaceutical ingredients, excipients, formulation, taxation, and 10% profit margin., Results: National prices of antiobesity medications were significantly higher than calculated EMPs. Semaglutide 30-day course prices ranged from $804 (United States) to $95 (Turkey) while the EMP was $40. Liraglutide prices ranged from $1418 (United States) to $252 (Norway) while the EMP was $50. Some oral treatments could be generically manufactured at very low costs per course ($7 for orlistat; $5 for phentermine/topiramate combination tablets), while naltrexone/bupropion was more expensive ($54)., Conclusions: This study shows that certain weight loss treatments can be manufactured and sold profitably at low costs, but prices currently range widely between countries, limiting access for those in need., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background & Aims: Pharmacological management of obesity improves outcomes and decreases the risk of obesity-related complications. This American Gastroenterological Association guideline is intended to support practitioners in decisions about pharmacological interventions for overweight and obesity., Methods: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis of the following agents: semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate extended-release (ER), naltrexone-bupropion ER, orlistat, phentermine, diethylpropion, and Gelesis100 oral superabsorbent hydrogel. The guideline panel used the evidence-to-decision framework to develop recommendations for the pharmacological management of obesity and provided implementation considerations for clinical practice., Results: The guideline panel made 9 recommendations. The panel strongly recommended the use of pharmacotherapy in addition to lifestyle intervention in adults with overweight and obesity (body mass index ≥30 kg/m 2 , or ≥27 kg/m 2 with weight-related complications) who have an inadequate response to lifestyle interventions. The panel suggested the use of semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate ER, and naltrexone-bupropion ER (based on moderate certainty evidence), and phentermine and diethylpropion (based on low certainty evidence), for long-term management of overweight and obesity. The guideline panel suggested against the use of orlistat. The panel identified the use of Gelesis100 oral superabsorbent hydrogel as a knowledge gap., Conclusions: In adults with overweight and obesity who have an inadequate response to lifestyle interventions alone, long-term pharmacological therapy is recommended, with multiple effective and safe treatment options., (Copyright © 2022. Published by Elsevier Inc.)

Objective: This study aimed to demonstrate noninferiority using telehealth in treating obesity with phentermine in patients with BMI ≥ 27 kg/m 2 with comorbidities or BMI ≥ 30 compared with the standard in-person approach over a 90-day period., Methods: A 12-week, randomized, prospective, single-center, open label trial compared the use of virtual visits versus in-person visits for the treatment of obesity using phentermine. The primary end point was percentage mean change in body weight from baseline to 12 weeks. A noninferiority approach assuming a 3% noninferiority region was used to assess effect size differences., Results: The weight loss in the virtual visit arm was noninferior to the in-person arm at all time points. At 12 weeks, the mean change in weight was -6.5% among the virtual group and -7.7% among the in-person group. In addition, 65% of virtual patients and 71% of in-person patients demonstrated a weight reduction of at least 5%. There was no difference in medication tolerance, adherence, and compliance., Conclusions: These results indicate that the virtual obesity pharmacotherapy visits in adults aged 18 to 65 years prescribed phentermine are effective and noninferior in achieving meaningful weight loss after 12 weeks. Future clinical trials are needed to better assess the effectiveness of televisits for obesity pharmacotherapy., (© 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Purpose of Review: Obesity is closely associated with nonalcoholic fatty liver disease (NAFLD), a highly prevalent disease without any approved medication. The aim of this review was to summarize the evidence on the effect of anti-obesity medications on NAFLD, especially focusing on hepatic histology., Recent Findings: Orlistat and some glucagon-like peptide-1 receptor analogs, including liraglutide and semaglutide, have beneficial effects on hepatic steatosis and inflammation, but not fibrosis. Other anti-obesity medications, including lorcaserin, setmelanotide, phentermine hydrochloric, phentermine/topiramate, and naltrexone/bupropion, have been minimally investigated in NAFLD. Furthermore, medications like sodium-glucose cotransporter-2 inhibitors and farnesoid X receptor have shown beneficial effects in both NAFLD and obesity, but they have not been licensed for either disease. Liraglutide, semaglutide, and orlistat may be currently used in selected patients with obesity and NAFLD. Further research is warranted, since targeting obesity may provide additional benefits on its comorbidities, including NAFLD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Modest weight loss (5%-10%) is clinically meaningful in patients with overweight or obesity. However, greater weight loss may be required to achieve improvements in or remission of certain weight-related complications. Therefore, this study reviewed the effect of large weight loss (≥10%). Most studies reporting large weight loss and relevant outcomes used bariatric surgery or lifestyle modifications., Results: Benefits of large weight loss were observed in patients with various overweight- or obesity-related complications, including improvements in comorbidities such as type 2 diabetes and hypertension. Improvements in glucose metabolism and cardiovascular risk factors were observed in patients who achieved large weight loss through lifestyle interventions or pharmacotherapy (phentermine/topiramate 15/92 mg once daily or subcutaneous semaglutide 2.4 mg once weekly). Other benefits associated with large weight loss included reduced cancer risk and improvements in knee osteoarthritis, sleep apnea, fertility-related end points, and health-related quality of life. While costly, bariatric surgery is currently the most cost-effective intervention, although most weight-management programs are deemed cost-effective., Conclusions: Overall, large weight loss has a major beneficial impact on overweight- and obesity-related complications. Large weight loss should be the main treatment target when modest weight loss has had insufficient effects on obesity-related complications and for patients with severe obesity., (© 2022 The Obesity Society.)

Metabolic risk for cardiovascular and other systems includes much more than just LDL cholesterol. This JCL Roundtable brings together 3 experts to address new opportunities to reduce the risks posed by obesity, diabetes, and fatty liver disease. Successful nutritional approaches to weight loss are diverse and need to be matched with individual preferences. Topiramate plus extended-release phentermine has been shown to promote meaningful weight loss in randomized trials, but the patented drug combination is expensive. Clinical experience suggests that generic topiramate and phentermine may also be effective. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown favorable tolerability and efficacy for cardiovascular disease in randomized trials, an achievement without precedent among earlier diabetes medications. These 2 drug classes differ in their effects. GLP-1 RAs decrease atherosclerotic cardiovascular events and also decrease hemoglobin A1c, body weight, blood pressure, and possibly diabetic renal disease. SGLT2 inhibitors are effective in reducing heart failure events even among nondiabetic patients. They also decrease progression of diabetic renal disease. The presence of nonalcoholic fatty liver disease signifies risk for atherosclerotic cardiovascular disease as well as cirrhosis and serious hepatic decompensation, including hepatocellular carcinoma. The key to identifying cirrhosis risk is to assess pre-emptively liver fibrosis, which can be predicted initially with blood test risk scores (e.g., FIB-4 index) and more definitively by transient elastography and other imaging techniques and/or liver biopsy. Some medications approved for the treatment of type 2 diabetes may reduce liver fat (SGLT2 inhibitors, insulin) or even reverse steatohepatitis in paired liver biopsy studies (GLP-1 RAs or pioglitazone) Overall the field of preventive metabolic medicine is expanding. Clinical lipidologists should become familiar with recent advances., (Copyright © 2022. Published by Elsevier Inc.)

Background and Aims: Randomized clinical trials have proven the efficacy and safety of Food and Drug Administration (FDA) approved anti-obesity medications (AOMs) for long-term use. It is unclear whether these outcomes can be replicated in real-world clinical practice where clinical complexities arise. The aim of this study was to evaluate the effectiveness and side effects of these medications in real-world multidisciplinary clinical practice settings., Methods: We reviewed the electronic medical records (EMR) of patients with obesity who were prescribed an FDA-approved AOM for long-term use in academic and community multidisciplinary weight loss programs between January 2016 and January 2020., Intervention: We assessed percentage total body weight loss (%TBWL), metabolic outcomes, and side effect profile up to 24 months after AOM initiation., Results: The full cohort consisted of 304 patients (76% women, 95.2% White, median age of 50 years old [IQR, 39-58]). The median follow-up time was 9.1 months [IQR, 4.2-14.1] with a median number of 3 visits [IQR, 2-4]. The most prescribed medication was phentermine/topiramate extended-release (ER) (51%), followed by liraglutide (26.3%), bupropion/naltrexone sustained-release (SR) (16.5%), and lorcaserin (6.2%). %TBWL was 5.0%, 6.8%, 9.3%, 10.3%, and 10.5% at 3, 6, 12, 18, and 24 months. 60.2% of the entire cohort achieved at least 5% TBWL. Overall, phentermine/topiramate-ER had the most robust weight loss response during follow-up, with the highest %TBWL at 12 months of 12.0%. Adverse events were reported in 22.4% of patients. Only 9% of patients discontinued the medication due to side effects., Conclusions: AOMs resulted in significant long-term weight loss, that was comparable to outcomes previously reported in clinical trials., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Orlistat, a reversible inhibitor of pancreatic and gastric lipase, is known to have anti-obesity and antioxidant properties. Cholesterol intermediates and metabolites have diverse and important functions in cardiovascular disease. Therefore, we aimed to evaluate the effect of orlistat on sterol metabolism in overweight and obese adults after weight loss during the intervention or weight loss at 12 weeks., Methods: A total of 51 (27 in the control group and 24 in the experimental group), patients with a BMI of 27 or greater were randomly assigned in a 1:1 ratio to receive either orlistat (120 mg) three times a day plus phentermine hydrochloride (37.5 mg) once daily or a placebo three times a day plus phentermine hydrochloride (37.5 mg) once daily. The primary study outcome was sterol metabolism., Results: The experimental group exhibited significantly decreased metabolic signatures of serum sterols, free cholesterol, sitosterol, 7α-hydroxycholesterol (7α-OHC), and 7β-OHC at 12 weeks. The experimental group also exhibited significantly decreased metabolic ratios of sitosterol and 7α-OHC to cholesterol at 12 weeks. Regarding changes in sterol signatures from baseline to 6-month follow-up, free cholesterol, plant sterols, and cholesterol precursors tended to decrease with weight loss during the intervention and increase again as the weight was regained in both groups., Conclusion: Orlistat treatment improves oxysterol metabolism in overweight and obese adults. Our findings support that orlistat plays a crucial role in the process of endothelial dysfunction and atherosclerosis via oxysterol modulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kwon, Kwon, Lee, Choi and Lee.)

Background: Obesity and eating disorders can present together, and pose diagnostic and therapeutic challenges to the clinician. Generally, lifestyle interventions alone for the treatment of obesity have modest long-term effectiveness. Phentermine-topiramate extended release is a relatively new medication approved for weight reduction. Sleep-related eating disorder is a rare condition that is often underdiagnosed. Both conditions are chronic and require long-term management. There is no definitive treatment for sleep-related eating disorder, and therapeutic options are based on case reports., Case Presentation: A 35-year-old Caucasian male with a body mass index of 41.7 kg/m 2 presented for obesity treatment. History revealed nocturnal episodes of hyperphagia associated with amnesia of overeating and other features of sleep-related eating disorder. Treatment was initiated with phentermine-topiramate extended release. Five months later he lost 5% of his body weight and demonstrated resolution of sleep-related eating disorder behaviors. He reported no adverse side effects. Upon self-discontinuation of the medication, his eating disorder recurred., Conclusions: Clinicians intending to help patients reduce body weight should screen for nocturnal eating and other eating disorders. Sleep-related eating disorder can be associated with significant morbidity and excess weight. Patients report adverse effects on quality of life as a result. Phentermine-topiramate extended release may be a good therapeutic option for patients presenting with comorbid obesity and sleep-related eating disorder. More research is needed to explore the efficacy and safety in this patient population., (© 2022. The Author(s).)

Objective: Hepatic steatosis is associated with increased surgical complications in bariatric surgery patients. We aimed to evaluate the effect of phentermine in reducing hepatic steatosis, adipose tissue, and surgical complications in patients undergoing bariatric surgery., Methods: This was a two-arm, double-blind, randomized, controlled pilot trial of 64 adult subjects with BMI >35 kg/m2 selected for bariatric surgery randomized into phentermine group (15 mg once daily) or placebo group for 8 weeks. Both groups adhered to a hypocaloric diet (500 calories/day) and an individualized exercise program. The primary endpoint was reducing the frequency of hepatic steatosis measured by ultrasound and reducing adipose tissue through fat mass in total kilograms or percentage. Key secondary points were the prevalence of surgical complications. Baseline and final biochemical parameters and blood pressure too were assessments., Results: In the phentermine group, the frequency of hepatic steatosis decreased by 19%, and the percentage of patients with a normal ultrasound increased from 9% to 28% (p = 0.05). Likewise, the decrease in fat mass in kilograms was more significant in the phentermine group (56.1 kg vs. 51.8 kg, p = 0.02). A significant reduction in the HOMA-IR index was observed regardless of weight loss. No differences in surgical complications were observed between groups. Phentermine was well-tolerated; no differences were observed in the frequency of adverse events between the groups., Conclusions: Phentermine decreased the proportion of individuals with hepatic steatosis by 19% and promoted a more significant fat mass loss in kilograms among candidates for bariatric surgery., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Older medications approved for chronic weight management (orlistat, naltrexone/bupropion, liraglutide 3 mg and, in the USA, phentermine/topiramate) have not been widely adopted by health care providers. Those medications produce only modest additional weight loss when used to augment lifestyle intervention. However, semaglutide 2.4 mg weekly has recently emerged and produces much more weight loss - on average 15% weight loss at 1 year. Semaglutide's enhanced efficacy and that its class (GLP-1 receptor analogs) is well-known may result in more clinicians adopting pharmacotherapy. Furthermore, the first dedicated cardiovascular outcome trial powered for superiority testing an anti-obesity medication (SELECT) is underway with semaglutide 2.4 mg. A positive outcome will further promote the concept that weight management should be a primary target for cardiometabolic disease control. In phase 3, tirzepatide and cagrilintide/semaglutide combination are showing promise for even greater weight loss efficacy. Another recently approved medication takes a personalized medicine approach; setmelanotide is approved as a therapy for those with some of the ultra-rare genetic diseases characterized by severe, early onset obesity. This chapter reviews the currently available and anticipated medications for chronic weight management as well as those approved for the genetic and syndromic obesities., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Hypertension is a major risk factor for cardiovascular and renal diseases in the United States and worldwide. Obesity accounts for much of the risk for primary hypertension through several mechanisms, including neurohormonal activation, inflammation, and kidney dysfunction. As the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed. Lifestyle modification, including diet, reduced sedentariness, and increased physical activity, is usually recommended for patients with obesity; however, the long-term success of these strategies for reducing adiposity, maintaining weight loss, and reducing blood pressure has been limited. Effective pharmacotherapeutic and procedural strategies, including metabolic surgeries, are additional options to treat obesity and prevent or attenuate obesity hypertension, target organ damage, and subsequent disease. Medications can be useful for short- and long-term obesity treatment; however, prescription of these drugs is limited. Metabolic surgery is effective for producing sustained weight loss and for treating hypertension and metabolic disorders in many patients with severe obesity. Unanswered questions remain related to the mechanisms of obesity-related diseases, long-term efficacy of different treatment and prevention strategies, and timing of these interventions to prevent obesity and hypertension-mediated target organ damage. Further investigation, including randomized controlled trials, is essential to addressing these questions, and emphasis should be placed on the prevention of obesity to reduce the burden of hypertensive cardiovascular and kidney diseases and subsequent mortality.

Aim: To assess the trends in the prescribing of antiobesity medications and the characteristics of patients recently initiating antiobesity drugs., Materials and Methods: We conducted a population-based cohort study using claims data from commercial health insurances in the United States. Patients initiating an antiobesity drug between January 2004 and December 2018 were included. Trends in the utilization of antiobesity medications were plotted by year, as a proportion of any antiobesity treatment, and as initiation rates per 100 000. Descriptive statistics were used to summarize the characteristics of antiobesity initiators., Results: From 2004 to 2018, 626 216 patients started an antiobesity medication (two per 100 000). Phentermine was the most frequently prescribed (50% in 2018). In recent years (2015-2018), among 227 692 patients who initiated an antiobesity drug, 51% started phentermine, 19% naltrexone-bupropion, and 13% liraglutide 3.0 mg. Compared to other agents, the use of liraglutide 3.0 mg increased between 2015 and 2018. The average age of initiators was 45 years, 81% of initiators were female, 32% had hypertension, 25% had dyslipidaemia, and 6% had type 2 diabetes. Time on treatment was generally short (mean 81 days)., Conclusion: The overall use of antiobesity medications remained low over the past 15 years and phentermine was the preferred antiobesity agent. Although the use of potentially safer antiobesity agents, for example, liraglutide 3.0 mg, has increased in recent years, phentermine remained the most frequently prescribed agent among middle-aged adults with a moderate burden of comorbidities., (© 2021 John Wiley & Sons Ltd.)

Purpose of Review: Weight regain after bariatric surgery is unfortunately a common occurrence. In this article, we have reviewed the data addressing this clinical problem focusing on pharmacological management of weight regain., Recent Findings: Data from several small, non-randomized, retrospective, and prospective studies provide evidence that a number of pharmacological options, both FDA approved and off-label, are effective in mitigating and managing weight regain after bariatric surgery. There is a suggestion that the optimal time to initiate weight loss medications may be at the time of weight plateau, rather than after weight regain. Adjuvant pharmacotherapy can help treat weight regain after bariatric surgery. Future studies should investigate the optimal timing for starting weight loss medications, as well as the best medication or combinations of medicines, for managing postoperative weight regain in different patient groups, including those who have undergone different types of bariatric surgeries.

Background and Aims: Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to >40% post-transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine-topiramate, naltrexone-bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs)., Approach and Results: While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine-topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed., Conclusions: The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co-morbidities, and concomitant medications., (© 2020 by the American Association for the Study of Liver Diseases.)

Purpose of Review: As a chronic and relapsing disease, obesity impairs metabolism and causes cardiovascular diseases. Although behavioral modification is important for the treatment of obesity, it is difficult to achieve an ideal weight or sustain the process of long-term weight loss. Therefore, the obesity control guidelines strongly recommend lifestyle interventions along with medical treatment for patients who are overweight. There is sufficient evidence supporting that pharmacotherapy in combination with behavior-based interventions can result in significant weight loss and improved cardiometabolism., Recent Findings: Recent meta-analyses of new anti-obesity drugs and their weight-loss efficacy have shown that the overall placebo-subtracted weight reduction (%) for at least 12 months ranged from 2.9 to 6.8% for the following drugs: phentermine/topiramate (6.8%), liraglutide (5.4%), naltrexone/bupropion (4.0%), orlistat (2.9%), and lorcaserin (3.1%). However, very recently, on February 13, 2020, the US Food and Drug Administration (FDA) ordered the withdrawal of lorcaserin from markets, as a clinical trial to assess drug safety showed an increased risk of cancer. Currently, the anti-obesity medications that have been approved by the FDA for chronic weight management are orlistat, phentermine/topiramate, naltrexone/bupropion, and liraglutide. However, they are costly and may have adverse effects in some individuals. Therefore, drug therapy should be initiated in obese individuals after weighing its benefits and risks. One of the strategies for long-term obesity control is that anti-obesity medications should be tailored for specific patients depending on their chronic conditions, comorbidities, and preferences.

Background: This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect., Objectives: Primary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).. Secondary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on change from baseline in systolic and diastolic blood pressure, and on body weight reduction., Search Methods: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work., Selection Criteria: Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo.  DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity., Main Results: This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes. There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) -2.6 mm Hg (95% confidence interval (CI) -3.8 to -1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD -2.0 mm Hg (95% CI -2.7 to -1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by -2.0 to -4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by -1.3 to -1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension., Authors' Conclusions: In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Rationale: Cocaine use disorder is an unrelenting public health concern. Despite nearly four decades of research, an FDA approved medication is not yet available., Objectives: The objective of this human laboratory study was to demonstrate the initial efficacy, safety and tolerability of topiramate-phentermine combinations for cocaine use disorder., Methods: Thirty-one (31) participants with cocaine use disorder completed this mixed-model inpatient laboratory study. Participants were maintained on topiramate (0 [N = 11], 50 [N = 9] or 100 [N = 11] mg/day). Each topiramate group was concurrently maintained on phentermine (0, 15, 30 mg). Drug self-administration, subjective responses and cardiovascular effects following acute doses of intranasal cocaine (0, 40, 80 mg) were determined during separate experimental sessions after at least seven (7) days of maintenance on each condition., Results: The three groups of participants were well matched demographically and generally did not differ significantly in their responses to a range of doses of intranasal cocaine (0, 10, 20, 40, 80 mg) during a medical safety session. Maintenance on topiramate and phentermine alone significantly decreased cocaine self-administration although these effects were modest in magnitude. Combining topiramate and phentermine robustly decreased cocaine self-administration. Topiramate and phentermine were well tolerated alone and combined, as well as in conjunction with cocaine., Conclusions: The results of the present study support advancing topiramate-phentermine combinations as a putative pharmacotherapeutic for cocaine use disorder., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Weight regain (WR) after Roux-en-Y gastric bypass surgery (RYGB) starts to occur 2 years after surgery, ultimately affecting at least 25% of patients. A limited number of studies have evaluated the impact of antiobesity medications (AOMs) on this phenomenon., Methods: This study reviewed the electronic medical records of 1,196 patients who underwent RYGB between 2004 and 2015. WR was evaluated by comparing each patient's weight during subsequent postoperative office visits to nadir weight (lowest weight after RYGB, n = 760), taking into consideration the interval during which WR occurred. Patients who were prescribed AOMs and came to follow-up visits were classified as adherent users, whereas those who missed their follow-up visits were considered nonadherent. This study used a linear mixed model, Cox regression, and generalized equation estimator to determine the impact of AOMs on WR trajectory, hazard ratio for time to event, and odds ratio for repeated event occurrence, respectively., Results: Despite the lack of a unified protocol for using AOMs, the three statistical models converged to show that phentermine and topiramate, used individually or in combination, can significantly reduce WR after RYGB., Conclusions: Phentermine and topiramate are effective in mitigating WR after RYGB. Further studies are needed to help ascertain optimal use of AOMs after bariatric surgery., (© 2020 The Obesity Society.)

Pharmacotherapy, adjunctively with lifestyle interventions, is an option for any patient diagnosed with obesity (ie, body mass index [BMI] of 30 kg/m 2 or greater) or with a BMI of 27 kg/m 2 or greater and at least one coexisting condition, including type 2 diabetes, hypertension, hyperlipidemia, and sleep apnea. If the appropriate criteria are met, pharmacotherapy should be initiated for patients with overweight or obesity if lifestyle modification does not produce adequate weight loss. Lifestyle modifications should be continued and emphasized throughout treatment because it has been shown that adjunctive pharmacotherapy produces greater weight loss and weight loss maintenance than lifestyle interventions alone. Currently, five drugs are approved for weight management in adults: phentermine, orlistat, phentermine-topiramate, bupropion-naltrexone, and liraglutide. Certain drugs are approved for short-term management while others are approved for long-term management. Drug therapy should be customized to the individual patient, depending on needs, contraindications, and cost. Benefits of these drugs should be assessed regularly and a different drug should be considered if at least 5% of body weight is not lost by 3 months of therapy., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

Aims: Over the past several decades, many antiobesity drugs have been withdrawn from the market due to unanticipated adverse events, often involving cardiotoxicity. This study aimed to evaluate the presence of cardiovascular safety signals with currently marketed antiobesity drugs., Methods: We used the US Food and Drug Administration Adverse Event Reporting System (FAERS) database and retrieved data from January 2013 through December 2018. We performed disproportionality analyses to detect cardiovascular safety signals with three antiobesity drugs recently approved for marketing: lorcaserin, naltrexone-bupropion, phentermine, and phentermine-topiramate. Three main cardiovascular outcomes were evaluated: valvular disorders, and pulmonary hypertension (PH) and other cardiovascular events (myocardial infarction, stroke, cardiovascular death, cardiac failure, and arrhythmia)., Results: During the evaluated period, a total of 6,787,840 adverse event reports were submitted to FAERS. Of these, 2687 involved lorcaserin, 3960 involved phentermine/phentermine-topiramate, and 2873 involved naltrexone-bupropion. Lorcaserin was associated with a significantly greater proportion of reports of valvular disorders (ROR = 4.39; 95% CI 2.72-5.07). None of the antiobesity drugs were associated with a safety signal for valvulopathy, PH, or other cardiovascular events., Conclusions: Our analyses revealed a signal for valvular disorders with lorcaserin and did not detect a safety signal for other cardiovascular events with recently approved antiobesity drugs. Further research is needed to explore and validate this signal.

Obesity, a chronic multifactorial disease, has been on the rise in the United States in recent years. It paves a way to other chronic conditions and related morbidity and mortality. The treatment of obesity should have a chronic approach involving lifestyle modifications from the very beginning. Along with reduced calorie diet, increased physical activity, and behavior modifications, various short- and long-term pharmacological agents are available to help with the weight loss. For qualifying patients, selection of an appropriate agent based on its mechanism, efficacy, and safety profile as well as patient preference can provide desired outcomes. This medical weight management should be a multidisciplinary approach involving nurses to provide continuous patient education and motivation.

Objective: Open trials suggest phentermine/topiramate ER (PHEN/TPM-ER), food and drug administration (FDA) approved for obesity, has utility for binge eating. With no randomized controlled trials (RCTs) yet performed, this trial aimed to evaluate PHEN/TPM-ERs efficacy and safety in a crossover RCT for patients with binge-eating disorder (BED) or bulimia nervosa (BN)., Method: Participants were randomized to 12-weeks PHEN/TPM-ER (3.75 mg/23 mg-15 mg/92 mg) or placebo followed by 2-weeks drug washout, then 12-week crossover. Demographics, vitals, eating disorder behaviors, mood, and side effects were measured. Primary outcome was objective binge-eating (OBE) days/4-weeks; secondary outcomes included binge abstinence. Mixed-effect models estimated treatment effects, with fixed effects adjusting for treatment, study period, and diagnosis., Results: The 22 adults (BED = 18, BN = 4) were female (96%), Caucasian (55%), aged 42.9 (SD = 10.1) years with body mass index = 31.1 (SD = 6.2) kg/m 2 . Baseline OBE days/4-weeks decreased from 16.2 (SD = 7.8) to 4.2 (SD = 8.4) after PHEN/TPM-ER versus 13.2 (SD = 9.1) after placebo (p < .0001), with abstinence rates = 63.6% on PHEN/TPM-ER versus 9.1% on placebo (p < .0001). Weight changes = -5.8 kg on PHEN/ TPM-ER versus +0.4 kg on placebo. Drop-out = 2 (9%) on PHEN/TPM-ER and 2 (9%) on placebo, with few side effects. Vital sign changes with PHEN/TPM-ER were minimal and similar to placebo. Responses were not significantly different for BED versus BN., Discussion: This first RCT to evaluate the efficacy and safety of PHEN/TPM-ER for BED/BN found this drug combination significantly more effective at reducing binge eating than placebo and well tolerated. However, with only four participants with BN, findings regarding the safety of PHEN/TPM-ER in patients with BN must be taken with caution., Trial Registration: Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824., (© 2019 Wiley Periodicals, Inc.)

Background: This pilot study evaluated whether adding phentermine to liraglutide would induce further weight loss in participants who had previously lost weight with liraglutide alone., Subjects/methods: Participants were 45 adults with obesity (75.6% female, 55.6% white, body mass index = 34.3 ± 4.7 kg/m 2 ) who had lost an average of 12.6 ± 6.8% of initial weight during a prior 1-year randomized trial with liraglutide and intensive behavioral treatment. Participants were re-randomized, in a double-blinded fashion, to liraglutide 3.0 mg plus phentermine 15.0 mg (liraglutide-phentermine) or liraglutide plus placebo (liraglutide-placebo). Participants also were provided with four, 15-minute counseling sessions during the 12-week extension study., Results: At week 12, the liraglutide-phentermine and liraglutide-placebo groups lost a mean (±SEM) of 1.6 ± 0.6% and 0.1 ± 0.5% of re-randomization weight, respectively (p = 0.073). Two (9.1%) liraglutide-phentermine participants and one (4.3%) liraglutide-placebo participant lost ≥5% of re-randomization weight; 19 (86.4%) and 16 (69.9%) participants, respectively, maintained their full weight loss achieved in the prior 1-year trial (p = 0.125). Liraglutide-phentermine participants generally reported larger reductions in hunger and food preoccupation than liraglutide-placebo participants during the first 8 weeks of the extension study., Conclusions: The combination of liraglutide and phentermine appeared to be well-tolerated but did not produce additional clinically meaningful weight loss in individuals who had already lost 12.6% of initial weight with liraglutide alone., Trial Registration: ClinicalTrials.gov number, NCT02911818., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Super obesity (body mass index [BMI] ≥50 kg/m 2 ) treatment can be complicated and high risk., Objectives: We studied whether the pre and postoperative use of phentermine and topiramate (phen/top) combined with laparoscopic sleeve gastrectomy (LSG) in super obesity increases the odds of achieving a BMI <40 at 2 years postoperatively., Setting: Academic medical center in Winston Salem, North Carolina., Methods: We recruited patients between 2014 and 2016 who had a BMI ≥50 and planned to undergo LSG (n = 25) to participate in an open-label trial. Participants took phen/top (7.5/46-15/92 mg/d) for at least 3 months preoperatively and 2 years postoperatively. We compared weight loss, BMI changes, and odds for achieving BMI <40 for phen/top + LSG to historical controls. Controls had an initial BMI ≥50 and underwent LSG, without phen/top, at our center during the same timeframe (n = 40)., Results: Of the 25 participants recruited, 13 completed LSG. Phen/top participants had a baseline BMI of 61.2 ± 7.1 kg/m 2 compared with 57.0 ± 5.6 kg/m 2 for control participants. Percent initial weight loss was -39.3% (phen/top + LSG) versus -31.4% (control) at 12 months, P = .018; by 24 months, phen/top + LSG had an 11.2% greater initial weight loss, P = .007. At 24 months, the mean BMI was 33.8 kg/m 2 for phen/top versus 42 kg/m 2 for controls. The odds ratio for achieving a BMI <40 at 2 years with phen/top + LSG versus LSG alone was 4.1 (95% confidence interval, 0.8-21)., Conclusions: Compared with LSG alone, phen/top combined with LSG may help patients with a BMI >50 achieve greater weight loss and reach a BMI <40. Long-term, controlled trials are needed to follow up these results., (Copyright © 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this work was to study weight loss and risk of cardiovascular disease (CVD) or death associated with longer-term phentermine use., Methods: Using electronic health record data, 13,972 adults were identified with a first phentermine fill in 2010 to 2015, creating exposure categories according to a patient's duration of use (referent: ≤ 3 months). Multivariable linear models were used to compare percent weight loss across categories at 6, 12, and 24 months, and Cox proportional hazards models were used to compare risk of composite CVD or death, up to 3 years after starting phentermine., Results: The cohort was 84% female and 45% white, with a mean (SD) baseline age 43.5 (10.7) years and BMI of 37.8 (7.2) kg/m 2 . In multivariable models, longer-term users of phentermine experienced more weight loss; patients using continuously for > 12 months lost 7.4% more than the referent group at 24 months (P < 0.001). The composite CVD or death outcome was rare (0.3%, 41 events), with no significant difference in hazard ratios between groups., Conclusions: Greater weight loss without increased risk of incident CVD or death was observed in patients using phentermine monotherapy for longer than 3 months. Despite the limitations of the observational design, this study supports the effectiveness and safety of longer-term phentermine use for low-risk individuals., (© 2019 The Obesity Society.)

Liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, and phentermine, a psychostimulant structurally related to amphetamine, are drugs approved for the treatment of obesity and hyperphagia. There is significant interest in combination use of liraglutide and phentermine for weight loss; however, both drugs have been reported to induce systemic hemodynamic changes, and as such the therapeutic window for this drug combination needs to be determined. To understand their impact on metabolic and cardiovascular physiology, we tested the effects of these drugs alone and in combination for 21 days in lean and obese male mice. The combination of liraglutide and phentermine, at 100 μg/kg/day and 10 mg/kg/day, respectively, produced the largest reduction in body weight in both lean and diet-induced obese (DIO) mice, when compared with both vehicle and monotherapy-treated mice. In lean mice, combination treatment at the aforementioned doses significantly increased heart rate and reduced blood pressure, whereas in DIO mice, combination therapy induced a transient increase in heart rate and decreased blood pressure. These studies demonstrate that in obese mice, the combination of liraglutide and phentermine may reduce body weight but only induce modest improvements in cardiovascular functions. Conversely, in lean mice, the additional weight loss from combination therapy does not improve cardiovascular parameters., (© 2019 by the American Diabetes Association.)

Introduction: Obesity is a growing health problem that has numerous comorbidities, including cardiovascular disease (CVD). The multi-disciplinary treatment of obesity now includes the use of pharmacotherapy. When treating patients with obesity and CVD, certain medications may be more appropriate than others., Areas Covered: Herein, the authors review the most commonly used FDA approved medications for the treatment of obesity, describing their mechanism of action, and the efficacy and safety of the medications as seen in recent studies, particularly in patients with CVD., Expert Opinion: In the population of patients with obesity and CVD, the medications orlistat, lorcaserin and liraglutide are considered the most appropriate options for their treatment, in terms of safety. Sympathomimetic medications, such as phentermine, should be avoided in this group. The recent CAMELLIA-TIMI 61 trial supports the safety of lorcaserin in patients with CVD. Until there are more studies, it is reasonable to extrapolate the findings of the LEADER trial, which found improved CV outcomes in subjects with type 2 diabetes taking liraglutide, to the population of nondiabetic patients being treated for obesity. Further cardiovascular outcomes trials (CVOT) are needed to assess the safety of other pharmacotherapeutic options for weight loss.

Objective: This study evaluated the effect of lorcaserin 10 mg twice daily (LOR BID), or with phentermine 15 mg once daily (LOR BID + PHEN QD) and 15 mg twice daily (LOR BID + PHEN BID), in conjunction with energy restriction on food cravings., Methods: Two hundred and thirty-five patients without diabetes but with obesity or overweight and ≥ 1 comorbidity received LOR BID, LOR BID + PHEN QD, or LOR BID + PHEN BID for 12 weeks in a randomized double-blind study. The Food Craving Inventory (FCI) and the Control of Eating Questionnaire (COEQ) were administered over 12 weeks., Results: The FCI total score and the subscale scores reduced from baseline in all groups. The least squares means (95% confidence intervals) for the total scores were -0.65 (-0.75 to -0.55), -0.75 (-0.84 to -0.65), and -0.84 (-0.95 to -0.74) in the LOR BID, LOR BID + PHEN QD, and LOR BID + PHEN BID groups, respectively. Cravings assessed by COEQ reduced from baseline in all groups. In general, the combination treatments were more effective than lorcaserin alone. At week 12, except for fruit juice and dairy products, general and specific cravings reduced in LOR BID + PHEN BID compared with LOR BID (P < 0.05)., Conclusions: Lorcaserin in combination with phentermine improves control of food cravings during short-term energy restriction., (© 2018 The Obesity Society.)

Introduction: Type 2 diabetes (T2DM) is associated with significant morbidity and mortality. Obesity is one of the main risk factors for T2DM and its management requires a multidisciplinary approach, which may include pharmacotherapy., Areas Covered: In this paper, data on efficacy, tolerability and safety of FDA-approved pharmacotherapies for obesity (orlistat, phentermine/topiramate extended-release, lorcaserin, bupropion sustained release/naltrexone sustained release and liraglutide) are reviewed, focusing on individuals with type 2 diabetes., Expert Opinion: Obesity is the major pathophysiologic driver of T2DM; conversely 5-10% weight loss leads to significant improvement in glycemic control, lipids and blood pressure. Weight loss maintenance is difficult with lifestyle interventions alone and may require adjunctive therapies. There is good evidence for the efficacy and tolerability of approved anti-obesity pharmacotherapies in individuals with T2DM, with current cardiovascular safety data being most favorable for liraglutide, orlistat and lorcaserin. Given the link between obesity and T2DM, a weight-centric therapeutic approach including use of weight reducing anti-diabetic therapies, and anti-obesity pharmacotherapies is both intuitive and rational to improve glycemic and other metabolic outcomes in patients with T2DM.

Introduction: Bulimia nervosa (BN) and binge eating disorder (BED) are associated with severe psychological and medical consequences. Current therapies are limited, leaving up to 50% of patients symptomatic despite treatment, underscoring the need for additional treatment options. Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER. Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine is FDA-approved for weight loss. A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy. While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We present a study protocol for a Phase I/IIa single-center, prospective, double-blinded, randomized, crossover trial examining safety and preliminary efficacy of Qsymia for BED and BN., Methods: Adults with BED (n=15) or BN (n=15) are randomized 1:1 to receive 12weeks Qsymia (phentermine/topiramate ER, 3.75mg/23mg-15mg/92mg) or placebo, followed by 2-weeks washout and 12-weeks crossover, where those on Qsymia receive placebo and vice versa. Subsequently participants receive 8weeks follow-up off study medications. The primary outcome is the number of binge days/week measured by EDE. Secondary outcomes include average number of binge episodes, percentage abstinence from binge eating, and changes in weight/vitals, eating psychopathology, and mood., Discussion: To our knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of phentermine/topiramate in BED and BN. We highlight the background and rationale for this study, including the advantages of a crossover design., Trial Registration: Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Although diet, physical activity, and behavioral modifications are the cornerstones of weight management, weight loss achieved by lifestyle modifications alone is often limited and difficult to maintain. Pharmacotherapy for obesity can be considered if patients have a body mass index (BMI) of 30 kg/m 2 or greater or BMI of 27 kg/m 2 or greater with weight-related comorbidities. The 6 most commonly used antiobesity medications are phentermine, orlistat, phentermine/topiramate extended release, lorcaserin, naltrexone sustained release (SR)/bupropion SR, and liraglutide 3.0 mg. Successful pharmacotherapy for obesity depends on tailoring treatment to patients' behaviors and comorbidities and monitoring of efficacy, safety, and tolerability., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Weight-loss drugs are being evaluated for their role in obesity management. This article reviews the available weight-loss drugs, their efficacy and side effects, and their best clinical use., (Copyright © 2017 Cleveland Clinic.)

Background and Purpose: To review the currently available pharmacotherapies for obesity management with a particular focus on the United States., Methods: Narrative review based on literature searches and the latest prescribing information (up to July 2017)., Conclusions: Obesity pharmacotherapies may assist those individuals who have obesity, or overweight with comorbidities, who have failed to maintain weight loss with lifestyle modifications alone (caloric restriction and increased physical activity). Currently approved options in the United States include phentermine for short-term use and five obesity pharmacotherapies that can be used long-term (orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion, and liraglutide 3.0 mg). If the use of an obesity pharmacotherapy is indicated, treatment should be selected to provide the most appropriate option for each individual and their circumstances. Variables such as contraindications, individual comorbidities, patient choice, patient readiness to incorporate additional behavioral changes (e.g., alcohol prohibition), and cost should guide choices., Implications for Practice: Each of the obesity pharmacotherapies has advantages and disadvantages that can help guide treatment choice. Those receiving treatment may also have individual preferences based on factors such as administration route, frequency of dosing, and/or safety profile. In addition, some options may be particularly appropriate for patients with common obesity-related complications such as depression or diabetes., (©2017 American Association of Nurse Practitioners.)

Background: Obesity is a major issue in Australia and globally. Many individuals struggle to maintain weight loss with lifestyle modification, and adjunctive pharmacotherapy may help. Historically, there have been limited pharmacotherapies for managing obesity. In addition, previous treatments such as phentermine-fenfluramine, rimonabant and sibutramine were withdrawn due to safety issues, resulting in lingering safety concerns., Methods: This is a narrative review of published data examining four new pharmacotherapy options for weight management in Australia. Of four new therapeutic options, three may be approved in Australia shortly and one - liraglutide 3.0mg - was approved in December 2015. Liraglutide is a glucagon-like peptide-1 receptor agonist that appears to act by increasing satiety and reducing food intake. Lorcaserin is a selective agonist of the serotonin 2C receptor, which mediates anorectic activity. The naltrexone/bupropion extended release (ER) combination utilises synergistic effects of the two component drugs, mediated via neurons in the hypothalamus, to reduce energy intake. Phentermine/topiramate ER combines the appetite suppressant phentermine with topiramate, an anti-epileptic with appetite-suppressant effects. All can result in meaningful improvements in obesity-related diseases, including diabetes and cardiovascular disorders) in large phase 3 trials, with efficacy demonstrated over 3 years for liraglutide 3.0 mg and 1-2 years for the rest., Conclusions: The landscape of obesity treatment is changing rapidly. Of the new therapeutic options presented, all options have associated adverse events requiring long-term safety data, but the availability of new options is a welcome development., (Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)