While bariatric surgery restults in significant long-term weight loss for most patients with obesity, post-surgical weight gain affects a considerable percentage of patients to varying degrees of severity. Furthermore, a small but significant percentage of patients experience inadequate post-surgical weight loss. Although many studies have examined the role of anti-obesity medications to address post-operative weight regain, an evidence-based consensus has not yet been achieved because of the heterogeneity of populations studied and the studies themselves. Observational studies in the post-bariatric surgery population consistently demonstrate the benefit of medical weight management after bariatric surgery, with most evidence highlighting liraglutide, topiramate, and phentermine/topiramate. New anti-obesity medications are anticipated to be helpful for post-surgical weight optimization given their efficacy in the non-surgical population.

Although drugs have been reported to modulate the gut microbiota, the effects of anti-obesity drugs on the gut microbiota remain unclear. Lorcaserin (LS) and phentermine (PT) are commonly used anti-obesity drugs. However, to our best knowledge, no studies have simultaneously assessed the effects of LS and PT on obesity and gut microbiota. This study aimed to explore the relationship between the anti-obesity effects of LS and PT and re-modulation of host gut microbiota. To test hypothesis, we fed C57BL/6J mice with a high-fat diet supplemented with LS and PT via oral gavage for 8 weeks. After sacrifice, body weight, fat accumulation, and serum biomarkers were measured, and the gut microbial composition was analyzed using 16 s rRNA amplicon sequencing. LS and PT were observed to modulate the gut microbial composition and restore gut microbial dysbiosis, as indicated by an increased Firmicutes/Bacteroidetes ratio. Significantly modulated genera by LS and PT treatment were strongly correlated with obesity-related markers. Additionally, LS and PT increased the mRNA level of G protein-coupled receptor 120 (GPR120) in the colon tissue. ASV3566, which corresponds to Eubacterium coprostanoligenes, was correlated with GPR120 and obesity-related markers such as glutamic pyruvic transaminase (GPT) and serum triglyceride (TG). In conclusion, LS and PT can modulate the gut microbiota dysbiosis and the gut microbiota plays a role in mediating the anti-obesity effect of drugs.

Obesity is a well-established cardiovascular (CV) risk factor with greater mortality and morbidity rates than the general population. Phentermine is a weight loss medication that is approved for short-term obesity treatment in conjunction with lifestyle modifications to decrease CV risk. A 51-year-old female with Raynaud's phenomenon who was started on phentermine one week prior presented with a one-day history of palpitations. Subsequent workup revealed non-ST elevation myocardial infarction (NSTEMI) on presentation and worsening ST segment depressions following regadenoson injection during pharmacological stress testing. Although current evidence suggests that the use of phentermine is safe and may even reduce the risk of CV disease in obese patients, it still may pose adverse CV effects. A detailed medical history, including medications used and predisposing conditions, is crucial to help identify and possibly prevent exacerbation of such CV side effects.

Background: Pharmacotherapy has emerged as a practical option for weight management in pediatrics. This study aims to assess the effectiveness and safety of phentermine use in pediatric patients with obesity. Methods: We performed a retrospective single-center analysis of patients younger than or equal to 18 years of age, over 10 years, who underwent phentermine treatment and recommended lifestyle changes. We evaluated efficacy by the change in the percent of the 95th percentile for BMI (%BMIp95). We deemed a 5% decrease in %BMIp95 as a favorable outcome. Results: We identified 30 pediatric patients who were treated with phentermine. The cohort was primarily female, 63% white, with a mean (standard deviation) baseline age of 15.63 (1.97) years. The average duration of treatment was 10 months, with a period ranging from 2 weeks to 2 years. The average %BMIp95 at the start of treatment was 137%, and that at the time of analysis was 122%, with a mean reduction of 15%. Five patients, 17%, experienced side effects that resolved after dose reduction or discontinuing phentermine. Conclusions: Phentermine monotherapy is an effective and safe means for weight loss in pediatric patients when combined with lifestyle interventions. Twenty-one of 30 (70%) patients achieved at least a 5% decrease in %BMIp95 within a mean duration of treatment of 10 months. We noted no severe adverse events.

The loss of function melanocortin 4-receptor (MC4R) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5-9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: -4.0 kg (-2.9%) in patient 1, and -1.8 kg (-1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (-2.9 kg; -2.8%). Phentermine treatment produced similar weight loss in six carriers (-12.7 kg; 15.5%) and 18 non-carriers (-11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.

Obesity might adversely affect the health and well-being of children and their families. Childhood obesity has crucial implications for health, both during childhood and as they age. It is highly associated with many acute problems and is commonly present during childhood, making visits and hospital admissions polarized in this group of children. The problems that may affect these children can be medical, such as asthma, chronic inflammation, orthopedic abnormalities, liver disease, diabetes mellitus or dyslipidemia. Long-term consequences of cardiovascular risk factors, the persistence of obesity and premature mortality are common among adults who had obesity during their early lives. Additionally, they could also suffer from psychological issues, such as low self-esteem, which puts them at risk of a much more serious psychosocial problem that may lead to depression, as well as a disruption in educational achievements and social relationships. A healthy diet, physical activity, adequate sleep, and limited screen time are all preventive measures that should be implemented at the family and community levels, preferably through well-structured programs. Furthermore, pharmacological management of childhood obesity is limited and only used after non-pharmacological interventions have failed or in the late stages of obesity. However, recent guidelines advocate the early use of medical interventions. Approved pharmacotherapeutic options include orlistat, phentermine/topiramate combination and liraglutide. There are several other options approved primarily for other specific forms of obesity or for other indications, including setmelanotide, metformin, lisdexamfetamine, zonisamide and fluoxetine. Bariatric surgery is a safe and effective option in cases with extreme obesity and comorbidities considering the need for long-term monitoring and support for cases and their families post-surgery. This review aims to discuss and highlight the recent evidence regarding risk factors, clinical consequences, prevention, and treatment of childhood obesity.

Obesity is a global epidemic with steadily increasing prevalence in most countries. Weight loss is generally challenging for patients to tackle in the face of the temptation to overeat and avoid physical activity. Hence, clinicians and patients alike are likely to steer toward the use of anorexigens. We report the case of a 33-year-old female with no significant cardiac history who presented with dyspnea, productive cough, and chest pressure for one month and was diagnosed with new-onset heart failure with a reduced ejection fraction secondary to prolonged phentermine use. The authors aim to highlight phentermine's potential for precipitating heart failure, even in a young, relatively healthy person, especially with a growing obese population. Ultimately, healthy weight loss can be achieved by implementing dietary changes and encouraging adequate physical activity, as the World Health Organization (WHO) recommended. Anorectic drugs may be employed for short-term use. Further research concerning the long-term side effects of phentermine may avert the prescriber and patient from abusing this drug.

Type 2 diabetes mellitus (T2DM) in adolescents is a more rapidly progressive disease, associated with earlier and higher rates of microvascular complications than in adults. As obesity is a significant risk factor for T2DM development and progression, the American Diabetes Association (ADA) recommends anti-obesity medications (AOMs) as adjuvant therapy for adults with both T2DM and overweight/obesity. In adults, the addition of AOMs to a diabetes regimen can improve glycemic control, reduce weight, and decrease anti-diabetes medication use. The ADA recommends considering bariatric surgery for adolescents with T2DM who have a BMI >35 kg/m2, but did not mention the use of AOMs in their 2022 updated guidelines. Currently, there are three FDA-approved AOMs available for chronic use in adolescents with obesity. Other medications are used in an "off-label" fashion for appetite suppression and BMI reduction. As additional AOMs are being developed and FDA-approved for the pediatric population, new treatment options with novel mechanisms of action will become available for adolescents with T2DM and obesity. In this review, we will discuss the evidence for the use of AOMs in the treatment of T2DM in adolescents, including lessons learned from the adult T2DM literature.

Obesity is a recently defined illness whose diagnosis and treatment continue to be stigmatized. Currently, due to lifestyle changes brought on by technological advancements and the wide availability and affordability of high-calorie foods, millions of people around the world suffer from obesity and/or its sequelae. Finding adequate prevention and treatment options would therefore lead to massive improvements in the duration and quality of life of affected individuals. In this review, we searched the PubMed database for studies exploring the safety and efficacy of the five medications currently approved by the FDA for the treatment of obesity. We included only studies pertaining to adult patients that have been published between 2012 and 2022. We found evidence that all the drugs analyzed such as orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, and semaglutide appear to be effective in inducing weight loss, with the suggestion that semaglutide may have superior efficacy. However, a massive obstacle in developing treatment guidelines remains the lack of prolonged studies monitoring the long-term safety and efficacy of obesity medications. Nevertheless, in patients at risk of complications from obesity, the benefits of losing fat mass may outweigh the potential side effects associated with these medications and clinicians should prescribe whichever of the FDA-approved pharmacotherapy they deem most appropriate for the patient's specific set of circumstances.

The Mali National Malaria Control Program (NMCP) recently established a phased set of goals for eliminating malaria in Mali by 2030. Over the past decade, the scale-up of NMCP-led malaria control interventions has led to considerable progress, as evidenced by multiple malariometric indicators. The West Africa International Center of Excellence in Malaria Research (WA-ICEMR) is a multidisciplinary research program that works closely with the NMCP and its partners to address critical research needs for malaria control. This coordinated effort includes assessing the effectiveness of control interventions based on key malaria research topics, including immune status, parasite genetic diversity, insecticide and drug resistance, diagnostic accuracy, malaria vector populations and biting behaviors, and vectorial capacity. Several signature accomplishments of the WA-ICEMR include identifying changing malaria age demographic profiles, testing innovative approaches to improve control strategies, and providing regular reporting on drug and insecticide resistance status. The NMCP and WA-ICEMR partnership between the WA-ICEMR and the NMCP offers a comprehensive research platform that informs the design and implementation of malaria prevention and control research programs. These efforts build local expertise and capacity for the next generation of malaria researchers and guide local policy, which is crucial in sustaining efforts toward eliminating malaria in West Africa.

Mass spectra are an important signature by which compounds can be identified. We recently formulated a mathematical approach for incorporating measurement variability when comparing sets of high-resolution mass spectra. Leveraging replicate mass spectra, we construct high-dimensional consensus mass spectra-representing each of the compared analytes-and compute the similarity between these data structures. In this paper, we present this approach and discuss its applications and limitations when trying to discriminate methamphetamine and phentermine using in-source collision induced dissociation mass spectra collected with direct analysis in real time mass spectrometry.

Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and affects a considerable proportion of the general population worldwide. Obesity is a major risk factor for development and progression of NAFLD and weight loss is an effective intervention for the management of NAFLD. However, few patients achieve substantial and sustained weight loss with lifestyle measures. Therefore, antiobesity agents are frequently considered in patients with NAFLD but there are limited data on their safety and efficacy. In the present review, we discuss the role of antiobesity agents in the management of NAFLD. All approved antiobesity agents appear to reduce transaminase levels and to improve steatosis in patients with NAFLD. However, their effects on fibrosis are less well studied and whether they affect liver-related outcomes, including progression to cirrhosis and hepatocellular cancer, is unknown. The glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, appear to represent a first-line option in obese patients with NAFLD and type 2 diabetes mellitus (T2DM) since they induce considerable weight loss and have been extensively studied in patients with T2DM. However, more studies are needed to evaluated their effects on liver-related and cardiovascular outcomes in patients with NAFLD, particularly in those without T2DM.

Obesity is characterized by visceral fat accumulation and various metabolic disturbances that cause metabolic syndrome and obesity-related cardiovascular diseases (ORCVDs). Hence, treatments targeting obesity should also prevent ORCVDs. Nonetheless, lifestyle modification therapy alone is still insufficient to reduce the risk of ORCVDs, although most cardiovascular guidelines still list it as the only treatment for obesity. Additionally, conventional anti-obesity drugs, such as orlistat, phentermine-topiramate, and naltrexone-bupropion, can reduce body weight but have not demonstrated a clear reduction in the risk of ORCVDs. To overcome this unmet clinical need, newer anti-obesity drugs must exhibit not only sufficient and long-lasting weight loss but also obvious cardiovascular benefits. Given recent clinical findings and evidences, in this context glucagon-like peptide-1 receptor agonist is currently available as a candidate that is clinically positioned as a first-line anti-obesity agent for the effective prevention of ORCVDs in people with obesity.

Phentermine/topiramate extended-release capsule (Qsymia®) is a fixed-dose combination of phentermine and topiramate, which is being developed by VIVUS (a subsidiary of Icahn Enterprises) for the treatment of obesity, sleep apnoea syndrome, type 2 diabetes mellitus and non-alcoholic steatohepatitis (NASH). The once-daily formulation of phentermine (a sympathomimetic amine) and topiramate is designed to combat obesity by decreasing appetite and increasing satiety. In July 2022, phentermine/topiramate received its first approval in the USA, as an adjunct to a reduced-calorie diet and increased physical activity, for chronic weight management in pediatric patients aged ≥ 12 years with BMI in the 95th percentile or greater standardized for age and sex. Phentermine/topiramate is approved in the US and South Korea for obesity in adults. Clinical development of phentermine/topiramate for sleep apnoea syndrome and type-2 diabetes in obese patients and preclinical development for NASH is ongoing in the US. This article summarizes the milestones in the development of phentermine/topiramate leading to this pediatric first approval for chronic weight management in adolescents.

This sheet talks about exposure to phentermine in a pregnancy and while breastfeeding. This information should not take the place of medical care and advice from your healthcare provider.

Suicide remains a global public health concern and the increased supply and use of synthetic stimulants globally may have implications for the burden of suicides attributable to substance use. This systematic review investigated any potential associations of stimulant use detected in post-mortem biological specimens and suicides. We conducted a systematic review and narrative synthesis (CRD42021237966). Medline, EMBASE, TOXLINE, and Scopus databases were searched for terms related to forensic toxicology, post-mortem toxicology, suicide and stimulants. The primary outcome was to estimate the prevalence of stimulant use in suicides. There were 26 studies whichcontributed to prevalence measures; in studies reporting at the individual compound level, suicides involved cocaine (0.1-23%), caffeine (3.2-22%), 3,4-methylenedioxymethamphetamine (0.1-17%), amphetamine (0.2-9.3%), methamphetamine (3.1-7%), and phentermine (0.9-1%). Overall, stimulant use in suicides was over-represented compared to estimates of stimulant use in the general population and has increased over time. Thirteen case reports used to contextualise suicides involving stimulants found no examples of cocaine or methamphetamine mono-intoxication of suicidal intent. This suggests mechanisms other than acute toxicity involved in stimulant-associated suicide. Future research by in-depth psychological autopsies of suicides involving stimulants, in combination with segmental hair analysis to determine the chronicity of stimulant exposure, may contribute to a better understanding of the burden of suicide attributable to stimulant use.

No information is available on the use of phentermine during breastfeeding. Phentermine and its combination with topiramate are not recommended during breastfeeding.

BACKGROUND: The rising prevalence and associated public health burden of obesity has led to advancements in pharmaceuticals for weight management. Semaglutide 2.4 mg, an anti-obesity medication (AOM) recently approved by the US Food and Drug Administration, has demonstrated clinically relevant weight loss in its phase 3 clinical trials. Economic evaluation comparing semaglutide 2.4 mg with other available weight management therapies is essential to inform payers for decision-making. OBJECTIVES: To assess the cost-effectiveness of semaglutide 2.4 mg in the treatment of adult patients with obesity (ie, body mass index [BMI] ≥ 30) and adult patients who are overweight (ie, BMI 27-29.9) with 1 or more weight-related comorbidities from a US third-party payer perspective. METHODS: A cohort Markov model was constructed to compare semaglutide 2.4 mg with the following comparators: no treatment, diet and exercise (D&E), and 3 branded AOMs (liraglutide 3 mg, phentermine-topiramate, and naltrexone-bupropion). All AOMs, including semaglutide 2.4 mg, were assumed to be taken in conjunction with D&E. Changes in BMI, blood pressure, cholesterol level, experience of acute and chronic obesity-related complications, costs, and quality-adjusted life years (QALYs) were simulated over 30 years based on pivotal trials of the AOMs and other relevant literature. Drug and health care prices reflect 2021 standardized values. Cost-effectiveness was examined with a willingness-to-pay (WTP) threshold of $150,000 per QALY gained. Sensitivity analyses were conducted to test the robustness of the cost-effectiveness results to plausible variation in model inputs. RESULTS: In the base-case analysis, treatment with semaglutide 2.4 mg was estimated to improve QALYs by 0.138 to 0.925 and incur higher costs by $3,254 to $25,086 over the 30-year time horizon vs comparators. Semaglutide 2.4 mg is cost-effective against all comparators at the prespecified WTP threshold, with the incremental cost per QALY gained ranging from $23,556 to $144,296 per QALY gained. In the sensitivity analysis, extended maximum treatment duration, types of subsequent treatment following therapy discontinuation, and weight-rebound rates were identified as key drivers for model results. The estimated probability of semaglutide 2.4 mg being cost-effective compared with comparators ranged from 67% to 100% when varying model parameters and assumptions. CONCLUSIONS: As a long-term weight management therapy, semaglutide 2.4 mg was estimated to be cost-effective compared with no treatment, D&E alone, and all other branded AOM comparators under a WTP threshold of $150,000 per QALY gained over a 30-year time horizon. DISCLOSURES: Financial support for this research was provided by Novo Nordisk Inc. The study sponsor was involved in several aspects of the research, including the study design, the interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication. Dr Kim and Ms Ramasamy are employees of Novo Nordisk Inc. Ms Kumar and Dr Burudpakdee were employees of Novo Nordisk Inc at the time this study was conducted. Dr Sullivan received research support from Novo Nordisk Inc for this study. Drs Wang, Song, Wu, Ms Xie, and Ms Sun are employees of Analysis Group, Inc, who received consultancy fees from Novo Nordisk Inc in connection with this study.

In this study representation of chemical substances in IDMP is reviewed, with an exploration of aggregation levels for substance used in the virtual drug data models of RxNorm, SNOMED-CT, ATC/INN, and the Belgian SAM database, for products with a single substance and combinations of substances. Active moiety and available solid states forms are explored for diclofenac, amoxicillin, carbamazepine, amlodipine, with regard to their representation in coding systems such as WHODrug, SMS, UNII, CAS, and SNOMED-CT. By counting the number of medicinal products in Belgium for amlodipine in each level of aggregation, concepts for grouper of substances and two levels of grouper of medicinal products are illustrated. Recommendations are made for the further development of IDMP and its link to international drug classifications.