Weight loss medication prescription prevalence in the active component, 2018-2023.

The U.S. military has witnessed rising obesity among active component service members. The Department of Defense authorized coverage of weight loss medications in 2018, but no study has evaluated prescription prevalence within the active component. This descriptive retrospective cohort study analyzed data from active component U.S. military service members from January 2018 through June 2023. The study used data from the Defense Medical Surveillance System to determine prescription period prevalence of weight loss medication. Data on demographics, body mass index, and history of diabetes were considered. The study revealed a 100-fold increase in the prescription period prevalence of weight loss agents in the active component from their initial authorization date. Demographics associated with higher prescription period prevalence were non-Hispanic Black race and ethnicity, female sex, and older age. Service members in the health care occupations and the Navy had higher prevalence compared to other service branches and occupations. The findings indicate a significant rise in the period prevalence of weight loss prescriptions over time. Further research is recommended to assess the effectiveness, safety, and use in austere military environments.

Effects of phentermine / topiramate extended-release, phentermine, and placebo on ambulatory blood pressure monitoring in adults with overweight or obesity: A randomized, multicenter, double-blind study.

Background: A fixed-dose combination of phentermine and extended-release topiramate (PHEN/TPM - approved for weight management) has demonstrated in-clinic reduction of blood pressure (BP). Ambulatory BP monitoring (ABPM) may be a better predictor of cardiovascular disease risk than in-clinic BP. Methods: This randomized, multicenter, double-blind study enrolled 565 adults with overweight/obesity. Inclusion criteria included participants willing to wear ABPM device for 24 h. Exclusion criteria included screening blood pressure >140/90 mmHg and antihypertensive medications not stable for 3 months prior to randomization. Participants received placebo (n = 184), phentermine 30 mg; (n = 191), or PHEN 15 mg/TPM 92 mg; (n = 190). 24-hour ABPM was performed at baseline and at week 8. The primary endpoint was mean 24-h systolic BP (SBP) as measured by ABPM, in the per protocol population. Results: Participants were mostly female (73.5 â€‹%) and White (81.6 â€‹%), with a mean age of 53.4 years; 32.4 â€‹% had no hypertension diagnosis or treatment, 62.5 â€‹% had hypertension using 0 to 2 antihypertensive medications, and 5.1 â€‹% had hypertension using ≥ 3 antihypertensive medications. Baseline mean SBP/diastolic BP (DBP) was 123.9/77.6 â€‹mmHg. At week 8, mean SBP change was -0.1 â€‹mmHg (placebo), +1.4 â€‹mmHg (phentermine 30 â€‹mg), and -3.3 â€‹mmHg (PHEN/TPM). Between-group difference for PHEN/TPM versus placebo was -3.2 â€‹mmHg (95 â€‹% CI: -5.48, -0.93 â€‹mmHg; p â€‹= â€‹0.0059). The between-group difference for PHEN/TPM versus phentermine 30 â€‹mg was -4.7 â€‹mmHg (95 â€‹% CI: -6.96, -2.45 â€‹mmHg; p â€‹< â€‹0.0001). Common (>2 â€‹% in any treatment group) adverse events (i.e., dry mouth, constipation, nausea, dizziness, paresthesia, dysgeusia, headache, COVID-19, urinary tract infection, insomnia, and anxiety) were mostly mild or moderate. Conclusions: In this randomized, multicenter, double-blind ABPM study, PHEN/ TPM reduced SBP compared to either placebo or phentermine 30 mg (Funding: Vivus LLC; ClinicalTrials.gov: NCT05215418).

Phentermine in the Modern Era of Obesity Pharmacotherapy: Does It Still Have a Role in Treatment?

PURPOSE OF REVIEW: This review provides an overview of the history, mechanism of action, and expected treatment effects of the anti-obesity medication (AOM), phentermine. It also includes a summary of recent research and practical guidance for prescribing clinicians. RECENT FINDINGS: Recent research on phentermine is sparse and consists primarily of observational studies with methodologic limitations. These studies suggest that phentermine use is associated with clinically significant weight loss in adults and that the medication is generally well tolerated. Large-scale observational studies evaluating phentermine's safety have not identified an increased risk of cardiovascular events or elevations in blood pressure. There is no data to support the notion that phentermine is addictive. Although it remains the most commonly prescribed AOM in the USA, phentermine has little rigorous research to support its efficacy and safety in long-term treatment, which creates a dilemma with guideline-recommended chronic use of AOMs. While we await forthcoming conclusive data on this front, clinicians may consider using phentermine long-term in selected patients, if such prescribing is consistent with local regulatory statutes.

SMART use of medications for the treatment of adolescent severe obesity: A sequential multiple assignment randomized trial protocol.

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.

Effects of Pharmacotherapy for the Treatment of Obesity in an Urban, Safety-Net Population.

OBJECTIVE: To evaluate the effect of common weight loss pharmacotherapies among low-income, racially diverse adult patients at an urban safety-net weight management clinic. METHODS: Our retrospective review from 2015 to 2019 examined patients who took either GLP-1 analog (GL) or phentermine/topiramate (PT) for ≥90 days and patients who exclusively pursued non-pharmacologic treatment for comparison. Changes in weight, blood pressure, and hemoglobin A1c at 1-year follow-up were reported. RESULTS: We analyzed 22 GL and 26 PT patients and included 40 patients who pursued only lifestyle modifications (LM). All three groups achieved significant weight loss at one year: GL -3.69 (interquartile range (IQR): -11.0, -1.77) kg (p=0.0004), PT -7.01 (IQR: -13.4, -1.45) kg (p<0.001), and LM -3.01 (IQR: -6.81, 1.13) kg (p=0.005). There was no significant difference in the median weight loss (p=0.11) between the three groups. We observed no significant changes in systolic blood pressure but saw a significant change of -0.75 in hemoglobin A1c (IQR: -1.35, -0.25) (p=0.01) among patients with diabetes in the GL group. CONCLUSIONS: Our real-world applications of GLP-1 and phentermine/topiramate suggest that both are effective weight loss medication regimens in low-socioeconomic status patients.

The Use of Phentermine for Obesity in Psychiatric Patients With Antipsychotics.

OBJECTIVE: Phentermine is a commonly used weight-loss agent in the United States, but there is a little information about the use of phentermine for patients with obesity taking antipsychotic medications. METHODS: We gathered 57 patients with obesity taking antipsychotic medications whose phentermine treatment was simultaneous with or after any type of antipsychotic exposure and collected data of clinical information, initial/follow-up anthropometric variables, and adverse events (AEs) for the 6-month study period. RESULTS: In total, the mean body weight reduction (BWR) was 4.45 (7.04) kg, and the mean BWR percent (BWR%) was 3.92% (6.96%) at 6 months. Based on the response to phentermine, the patients were classified into two groups: the responder (n=25; BWR% ≥5%) and nonresponder (n=32; BWR% <5%) groups. The responder group's mean BWR and BWR% were 10.13 (4.43) kg and 9.35% (4.09%), respectively, at 6 months. The responders had higher rates of anticonvulsant combination therapy (ACT; responder, 72.0% vs. non-responder, 43.8%; p=0.033) and a shorter total antipsychotic exposure duration (responder, 23.9 [16.9] months vs. non-responder, 37.2 [27.6] months; p= 0.039). After adjusting age, sex, and initial body weight, ACT maintained a significant association with phentermine response (odds ratio=3.840; 95% confidence interval: 1.082-13.630; p=0.037). In the final cohort, there was no report of adverse or new-onset psychotic symptoms, and the common AEs were sleep disturbances, dry mouth, and dizziness. CONCLUSION: Overall, phentermine was effective and tolerable for patients with obesity taking antipsychotic medications, and ACT (predominantly topiramate) augmented the weight-loss effect of phentermine.

A narrative review of approved and emerging anti-obesity medications.

Background: Recently, many drugs have been approved for halting overweight and obesity-few types of research shifted to using Anti-obesity medications (AOM) solely for well-being and shape-keeping. Objective: This narrative review's objective was to explore the use of AOM in relation to their medical indications, efficacy, and cardiovascular safety. Methods and materials: We have conducted a narrative review of the literature on approved/non-approved AOM used for obesity and overweight. We have shed light on the emerging trials of therapies and evolving remedies. Results: Recently, there has been an enormous change in the use of AOM with high consumption that deserves extensive surveillance for the long-term consequences and impact on social, mental, and physical health. Nearly six AOMs and combined therapy are approved by the Food and Drug Administration. The recent guidelines for obesity management have shifted the focus from weight loss to goals that the patient considers essential and toward targeting the root cause of obesity. Conclusion: The use of AOM increased enormously despite its sometimes-dubious safety and ineffectiveness. The public and medical professionals should be vigilant to the real-world benefits of anti-obesity drugs and their achieved effectiveness with an improved safety profile.

Pharmacokinetic and pharmacodynamic interaction of DWP16001, a sodium-glucose cotransporter-2 inhibitor, with phentermine in healthy subjects.

BACKGROUND: DWP16001, a sodium-glucose cotransporter-2 inhibitor, has shown promise for improving blood glucose control and facilitating weight loss. Co-administration with phentermine could enhance these effects. So, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions of DWP16001 and phentermine. METHODS: We conducted a randomized, open-label, 3-treatment, 6-sequence, 3-period crossover study involving 24 healthy adults. Participants received either DWP16001 (2 mg), phentermine (37.5 mg), or a combination of both once daily for 7 days. Blood samples, urine samples, and body weights were collected to evaluate the PK and PD. RESULTS: The PK of the combination was found to be similar to that of the monotherapy. The geometric mean ratio (GMR) of Cmax,ss, and AUCtau,ss were 0.98 and 1.00, respectively, for DWP16001, and 1.01 and 0.94, respectively, for phentermine. Co-administration did not significantly affect the 24-hour urinary glucose excretion compared to DWP16001 monotherapy, and the GMR was 0.90. Participants tended to experience greater weight loss in the combination therapy group, and all demonstrated good tolerance. CONCLUSIONS: Our findings indicate that there were no significant interactions during co-administration. These results suggest that the combination of DWP16001 and phentermine may be safe and effective for the treatment of obesity and diabetes. CLINICAL TRIAL REGISTRATION: NCT05321732.

Phentermine involvement in fatal drug overdoses in Tennessee, 2019-2022.

INTRODUCTION: Phentermine, one of the most-commonly prescribed pharmaceuticals for weight-loss in the United States (US), has appeared on toxicology and listed as a cause of death in fatal drug overdoses in the state of Tennessee. This study aims to evaluate phentermine's involvement in fatal drug overdoses in the state of Tennessee. METHODS: We used Tennessee State Unintentional Drug Overdose Reporting System (SUDORS) data and controlled substances monitoring program data (CSMD) to evaluate demographics, prescription history and co-occurring substances on toxicology in phentermine-positive cases compared with all other SUDORS cases from January 1, 2019 to June 30, 2022. A subset of these cases which listed phentermine as a cause of death was also assessed. RESULTS: We identified 51 phentermine-positive cases, with a subset of 20 that listed phentermine as a cause of death. When compared to all SUDORS cases, a higher proportion of cases that listed phentermine as a cause of death were White race, females, and aged 35-44. Additionally, in all phentermine-positive cases, 41% (21) of decedents had not had a phentermine prescription dating back to 2012 and 20% (Lee et al., 1998) did not have one within the last 30 days. While there was a slight decline each year in the number of phentermine-positive cases, the number of cases that listed phentermine as a cause of death remained relatively consistent, with 95% (19) of cases having different prescriptions and/or illicit drugs listed as a cause of death along with phentermine. CONCLUSION: Phentermine was listed as a cause of death in 20 fatal drug overdoses in TN. Our findings suggest there may be differences in the characteristics of these decedents when compared to all SUDORS decedents, including distribution of age, gender, and race. We also found a large presence of other prescription and illicit drugs in toxicology and cause of death along with phentermine, as well as evidence of use of the drug without a prescription. Given the lack of currently available data about non-prescribed phentermine use and its involvement in fatal drug overdoses elsewhere, a need exists to both expand surveillance capabilities and broaden research to better inform policies governing this drug in the US and internationally.

A Narrative Review: Phentermine and Topiramate for the Treatment of Pediatric Obesity.

The prevalence of pediatric obesity has increased exponentially over the past four decades. The American Academy of Pediatrics recently released updated clinical practice guidelines highlighting the importance of identifying pediatric obesity as a chronic disease. The guidelines support consideration of concurrent treatment with intensive lifestyle interventions, obesity pharmacotherapy, and bariatric surgery. The dramatic rise in pediatric obesity has spurred interest in utilizing obesity pharmacotherapy to support sustained weight reduction in pediatric cohorts, in the hopes of preventing the emergence of later-appearing, significant co-morbidities. Despite the enormous demand, the obstacles posed by performance of needed clinical trials in the pediatric population markedly limits available pharmacotherapy for the treatment of obesity in pediatrics. Currently, there are five medications approved by the Food and Drug Administration for use in youth with obesity. In 2022, the phentermine/topiramate (PHEN/TPM), once-daily, controlled-release, combination product received FDA approval, for the indication of chronic weight management, in youth with obesity, ages 12 years and older. The objectives of this narrative review are to: (1) Review the mechanism of action of phentermine and topiramate, (2) Summarize the safety and efficacy data of topiramate and phentermine use as both monotherapies and in combination, and (3) Discuss clinical practice guidelines and clinical implications, for the use of these agents in youths with obesity.

Combination therapy: A New Tool for the Management of Obesity.

Obesity is a long-term lifestyle problem that can lead to disastrous consequences. Lifestyle interventions are one of the initial lines of management strategies for obesity but in long term, it is not very effective in the management of obesity. Some people also manage their weight with bariatric surgery, which is now the most effective obesity treatment. Synthetic pharmaceuticals make a bridge between lifestyle modification and bariatric surgery-based obesity management. The major problem associated with monotherapy without side effects is that these are moderately effective and also need in higher doses. The 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 of actions for a better effect. The commonly used combination therapy for obesity management includes low-dose phentermine and prolonged and slow-releasing mechanism topiramate; naltrexone along with bupropion. Phentermine with inhibitors of Na-glucose cotransporter-2 or glucagon-like peptide-1 (GLP-1) agonist with gastric hormone or Na-glucose cotransporter-2 is two more viable combo therapy. This combination strategy aims to achieve success in the bariatric surgery and the scientific community is working in this direction.

Pharmacologic Treatment of Obesity in Reproductive Aged Women.

Purpose of Review: This report will review existing literature on weight loss outcomes for various anti-obesity medications (AOMs) as well as their effects on human fertility, pregnancy, or breastfeeding. Recent Findings: There is a paucity of research on the effects of AOMs on human pregnancy and fertility. The majority of AOMs are not recommended during pregnancy and breastfeeding due to known or unclear risks of harm to offspring. Summary: As the prevalence of obesity rises, AOMs have proven to be effective tools for weight loss in the general adult population. When prescribing AOMs to reproductive-aged women, providers should consider both the cardiometabolic benefits of these medications and potential effects that AOMs might have on hormonal contraception, pregnancy, or breastfeeding. Animal studies in rats, rabbits, and monkeys have suggested teratogenic effects of several medications discussed in this report. However, a lack of data on the use of many AOMs during human pregnancy or lactation makes it difficult to comment on the safety of their use in these time periods. Some AOMs show promise in promoting fertility while others might decrease the efficacy of oral contraceptives, highlighting some of the special considerations that must be taken when prescribing AOMs to reproductive-aged women. More research into the risks and benefits of AOMs in the context of reproductive-aged women's unique healthcare needs is an important step in improving this population's access to effective treatments for obesity.

Novel Anti-obesity Therapies and their Different Effects and Safety Profiles: A Critical Overview.

Obesity has become an epidemic and a worldwide problem and its treatment is ever-evolving. Apart from diet and exercise, medication and surgery are other options. After disappointing side effects of various obesity drugs, new treatments showed promising results. This review discusses the following anti-obesity drugs: liraglutide, semaglutide, tirzepatide, orlistat, as well as the phentermine/topiramate and bupropion/naltrexone combinations. These drugs have been approved by the Food and Drug Administration (FDA) for weight reduction except for tirzepatide which is still under evaluation. Efficacy and tolerable safety profiles of some of these drugs contribute to the management of obesity and reduce the complications associated with this chronic disease.

Synthesis of Phentermine and its derivatives..

In recent years, a growing global concern has been obesity. Patients with obesity are at major risk for developing several diseases. These diseases may significantly impact patients' daily lives and increase the mortality rate [1]. Over a year, medication for obesity has undergone substantial changes. An amphetamine-like prescription drug called Phentermine (Adipex-P, Lomaira) appetite. In the last few years, Phentermine and its derivatives have attracted much attention due to their use in weight reduction; by reducing appetite or prolonging the feeling of fullness, it can aid in weight reduction. So, reviewing the synthesis of Phentermine and its derivatives becomes imperative. Therefore, various synthetic routes for Phentermine (from benzaldehyde, isopropyl phenyl ketone, dimethyl benzyl carbinol) and its derivatives synthesis, involving ortho-palladation, are also reviewed here comprehensively.

Dilated Cardiomyopathy: Beware of Diet Drugs Slimming the Heart.

There have been rare reports of dilated cardiomyopathy from chronic use of phentermine/topiramate, although very limited data are available. Phentermine is an atypical amphetamine analog that has been contraindicated in patients with a history of cardiovascular disease. We present a case of nonischemic dilated cardiomyopathy in the setting of chronic phentermine/topiramate use, which is the most likely cause of her dilated cardiomyopathy.

Impact on Cardiovascular Health of Using Phentermine/Topiramate in Combination With Laparoscopic Sleeve Gastrectomy in Super Obesity.

INTRODUCTION: Management of patients with BMI≥50 kg/m2 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/m2 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/m2 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.

Real-World Experience of the Efficacy and Safety of Phentermine Use in Adolescents: A Case Series.

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.

A Rare Case of Phentermine-Induced Nonischemic Cardiomyopathy.

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.