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Endocrine, Metabolic & Immune Disorders... 2024Obesity 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... (Review)
Review
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.
Topics: Humans; Obesity; Anti-Obesity Agents; Drug Therapy, Combination; Phentermine; Treatment Outcome; Animals
PubMed: 37641995
DOI: 10.2174/1871530323666230825140808 -
Adolescent Health, Medicine and... 2023The prevalence of pediatric obesity has increased exponentially over the past four decades. The American Academy of Pediatrics recently released updated clinical... (Review)
Review
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.
PubMed: 37641650
DOI: 10.2147/AHMT.S383454 -
Journal of Managed Care & Specialty... Oct 2023Primary nonadherence (PNA), when a medication is newly prescribed but not filled, has been identified as a major research gap potentially impacting the optimal...
Primary nonadherence (PNA), when a medication is newly prescribed but not filled, has been identified as a major research gap potentially impacting the optimal treatment of patients with overweight and obesity who are newly prescribed antiobesity medications (AOMs). To assess PNA among patients with newly prescribed AOMs and to examine factors associated with PNA to AOMs. This was a retrospective study that used the Optum Integrated Clinical plus Claims database to identify individuals who had at least 1 prescription order for an AOM the US Food and Drug Administration approved for long-term use. Individuals with prescription orders between January 1, 2012, and February 28, 2019, were identified, and patient demographics, clinical characteristics, medication prescribed, baseline health care utilization, and obesity-related complications were described by PNA status. PNA was defined as no pharmacy claim for the AOM within 60 days of the date of the new prescription order as identified in electronic health record data. A multivariable logistic regression model was used to examine factors associated with PNA. The study sample included a total of 1,563 patients. The mean body mass index was 38.4 kg/m; 10.7% were prescribed liraglutide 3.0 mg, 26.0% were prescribed lorcaserin, 36.3% of patients were prescribed naltrexone-bupropion, 5.4% were prescribed orlistat, and 21.6% were prescribed phentermine-topiramate. Most patients (91.1%) exhibited PNA, with only 8.9% filling their newly prescribed AOM within 60 days. Both the adherent and nonadherent groups were predominately female sex, White, and covered by commercial insurance. The mean age was similar between the 2 groups. Most obesity-related complications were less prevalent in the adherent group, although the Charlson comorbidity index score was similar between the 2 groups. After adjustment for patient demographics and clinical characteristics, there was not a statistically significant association between the specific AOM and PNA ( = 0.299). Patients with depression or living in the Midwest or South regions were at significantly increased risk of PNA. The rate of PNA to AOMs was very high, suggesting barriers in effective medical management of patients with overweight and obesity. Future research is warranted to understand reasons for PNA to AOMs and how to address these barriers. Dr Kan, Dr Bae, Dr Dunn, and Dr Ahmad are employees of Eli Lilly and Company. Ms Buysman and Dr Gronroos are employees of Optum. Dr Swindle was an employee of Optum at the time the study was conducted and is currently employed at Evidera. Dr Bengtson is employed at Boehringer Ingelheim Pharmaceuticals, Inc. (Boehringer Ingelheim has no connection to this study), and during the conduct of this study was employed at Optum.
Topics: Humans; Female; Retrospective Studies; Overweight; Anti-Obesity Agents; Obesity; Delivery of Health Care
PubMed: 37594848
DOI: 10.18553/jmcp.2023.23083 -
Journal of Medicinal Chemistry Aug 2023The cardiotoxicity associated with -ethyl-dexfenfluramine (norDF) and related agonists of the serotonin receptor 2B (5-HT) has solidified the receptor's place as an... (Review)
Review
The cardiotoxicity associated with -ethyl-dexfenfluramine (norDF) and related agonists of the serotonin receptor 2B (5-HT) has solidified the receptor's place as an "antitarget" in drug discovery. Conversely, a growing body of evidence has highlighted the utility of 5-HT antagonists for the treatment of pulmonary arterial hypertension (PAH), valvular heart disease (VHD), and related cardiopathies. In this Perspective, we summarize the link between the clinical failure of fenfluramine-phentermine (fen-phen) and the subsequent research on the role of 5-HT in disease progression, as well as the development of drug-like and receptor subtype-selective 5-HT antagonists. Such agents represent a promising class for the treatment of PAH and VHD, but their utility has been historically understudied due to the clinical disasters associated with 5-HT. Herein, it is our aim to examine the current state of 5-HT drug discovery, with an emphasis on the receptor's role in the central nervous system (CNS) versus the periphery.
Topics: Humans; Receptor, Serotonin, 5-HT2B; Serotonin; Fenfluramine; Heart Valve Diseases; Drug Discovery
PubMed: 37584406
DOI: 10.1021/acs.jmedchem.3c01178 -
The International Journal on Drug Policy Sep 2023Phentermine, 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...
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.
Topics: Female; Humans; United States; Tennessee; Analgesics, Opioid; Phentermine; Drug Overdose; Illicit Drugs
PubMed: 37549596
DOI: 10.1016/j.drugpo.2023.104151 -
Pharmaceuticals (Basel, Switzerland) Jul 2023Recent media reports commented about a possible issue of the misuse of antidiabetics related to molecules promoted as a weight-loss treatment in non-obese people. We...
Recent media reports commented about a possible issue of the misuse of antidiabetics related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to , a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (, , , , , and ) and the - combination. To acheieve that aim, we analyzed the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AERs) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AERs involving the selected molecules were submitted to FAERS; most involved dulaglutide (n = 11,858; 37.6%) and semaglutide (n = 8249; 26.1%). In comparing semaglutide vs. the remaining molecules, the respective PRR values of the AERs 'drug abuse', 'drug withdrawal syndrome', 'prescription drug used without a prescription', and 'intentional product use issue' were 4.05, 4.05, 3.60, and 1.80 (all < 0.01). The same comparisons of semaglutide vs. the phentermine-topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misuse/abuse potential of semaglutide in comparison with other GLP1 analogues and the phentermine-topiramate combination. The current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.
PubMed: 37513906
DOI: 10.3390/ph16070994 -
Life (Basel, Switzerland) Jul 2023Obesity affects approximately 1 in 5 youth globally and increases the risk of complications during adolescence and young adulthood, including type 2 diabetes,... (Review)
Review
Obesity affects approximately 1 in 5 youth globally and increases the risk of complications during adolescence and young adulthood, including type 2 diabetes, dyslipidemia, hypertension, non-alcoholic fatty liver disease, obstructive sleep apnea, and polycystic ovary syndrome. Children and adolescents with obesity frequently experience weight stigma and have an impaired quality of life, which may exacerbate weight gain. Pediatric obesity is typically defined using sex-, age-, and population-specific body mass index percentiles. Once identified, pediatric obesity should always be managed with lifestyle modification. However, adolescents with obesity may also benefit from anti-obesity medications (AOM), several of which have been approved for use in adolescents by the US Food and Drug Administration, including liraglutide, phentermine/topiramate, and semaglutide. For children with specific, rare monogenic obesity disorders, setmelanotide is available and may lead to significant weight loss. Metabolic and bariatric surgery may be used for the management of severe obesity in youth; though highly effective, it is limited to specialized centers and has had relatively low pediatric uptake. In this narrative review using pediatric-focused data from original research, reviews, clinical practice guidelines, governmental agencies, and pharmaceutical companies, we review obesity-related metabolic complications in youth and management strategies, including AOM and bariatric surgery.
PubMed: 37511966
DOI: 10.3390/life13071591 -
Advances in Therapy Sep 2023Due to the diverse mechanisms of action of antiseizure drugs, there has been a rise in prescriptions of these drugs for non-epileptic pathologies. One drug that is now... (Review)
Review
Due to the diverse mechanisms of action of antiseizure drugs, there has been a rise in prescriptions of these drugs for non-epileptic pathologies. One drug that is now being used for a variety of conditions is topiramate. This is a narrative review that used PubMed, Google Scholar, MEDLINE, and ScienceDirect to review literature on the clinical and pharmacologic properties of topiramate. Topiramate is a commonly prescribed second-generation antiseizure drug. The drug works through multiple pathways to prevent seizures. In this regard, topiramate blocks sodium and calcium voltage-gated channels, inhibits glutamate receptors, enhances gamma-aminobutyric acid (GABA) receptors, and inhibits carbonic anhydrase. Topiramate is approved by the Food and Drug Administration (FDA) for epilepsy treatment and migraine prophylaxis. Topiramate in combination with phentermine is also FDA-approved for weight loss in patients with a body mass index (BMI) > 30. The current target dosing for topiramate monotherapy is 400 mg/day and 100 mg/day to treat epilepsy and migraines, respectively. Commonly reported side effects include paresthesia, confusion, fatigue, dizziness, and change in taste. More uncommon and serious adverse effects can include acute glaucoma, metabolic acidosis, nephrolithiasis, hepatotoxicity, and teratogenicity. Related to a broad side effect profile, physicians prescribing this drug should routinely monitor for side effects and/or toxicity. The present investigation reviews various anti-seizure medications before summarizing indications of topiramate, off-label uses, pharmacodynamics, pharmacokinetics, adverse effects, and drug-drug interactions.
Topics: Humans; Topiramate; Anticonvulsants; Fructose; Epilepsy; Migraine Disorders
PubMed: 37368102
DOI: 10.1007/s12325-023-02586-y -
Nature Reviews. Endocrinology Sep 2023Obesity is a common chronic disease in children and adolescents and its prevalence is increasing worldwide. The causes are multifactorial but involve biological... (Review)
Review
Obesity is a common chronic disease in children and adolescents and its prevalence is increasing worldwide. The causes are multifactorial but involve biological predisposition towards a specific body-weight set point and defended adipose tissue mass converging with an obesogenic environment. Comprehensive treatment of paediatric obesity includes lifestyle modification therapy, anti-obesity medications (AOMs) and/or metabolic surgery. Lifestyle modification therapy used alone produces fairly modest weight loss for most youth with obesity. The emergence of new AOMs has changed the landscape of paediatric weight management, improving the outlook for youth with obesity. This Review briefly highlights obesity development pathways in youth and the role that pharmacotherapy can play in counteracting these pathophysiological forces. Here, results from adolescent AOM clinical trials published since 2020 are reviewed, including the safety, efficacy and tolerability of the newest treatments (glucagon-like peptide 1 receptor agonists and phentermine-topiramate). The importance of a comprehensive and chronic care model, including both lifestyle modification and ongoing pharmacotherapy, will be discussed in the context of maximizing long-term health outcomes. Finally, insight will be provided into the emerging pipeline of AOMs (for example, incretin receptor co-agonists and tri-agonists) and how future therapies might fundamentally change the prognosis for youth with obesity.
Topics: Adolescent; Humans; Child; Pediatric Obesity; Topiramate; Fructose; Anti-Obesity Agents; Weight Loss
PubMed: 37337008
DOI: 10.1038/s41574-023-00858-9 -
Current Organic Synthesis 2024In recent years, a growing global concern has been obesity. Patients with obesity are at major risk for developing a number of diseases. These diseases may significantly... (Review)
Review
In recent years, a growing global concern has been obesity. Patients with obesity are at major risk for developing a number of diseases. These diseases may significantly impact patient's daily lives and increase the mortality rate. Over a year, medication for obesity has undergone substantial changes. An amphetamine-like prescription drug called Phentermine (Adipex-P, Lomaira) is used to suppress 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.
Topics: Phentermine; Humans; Appetite Depressants
PubMed: 37259208
DOI: 10.2174/1570179420666230530095245