-
Obesity Pillars Mar 2023Once thought to be primarily a result of lifestyle, it is now known that obesity has significant genetic components. Dozens of genes have been linked to obesity, and...
BACKGROUND
Once thought to be primarily a result of lifestyle, it is now known that obesity has significant genetic components. Dozens of genes have been linked to obesity, and office-based genetic testing for obesity-associated genes is now readily available. As both pharmacotherapy and genetic testing for obesity become more accessible, pharmacogenetic personalization is becoming a reality. In this case report, a patient with a PLXNA4 polymorphism had a superior weight loss response to phentermine/topiramate therapy than has previously been reported in the literature. Thus, variants in PLXNA4 may provide a genetic basis for this patient's superior response to weight loss pharmacotherapy and cardiovascular risk factor reduction.
METHODS
In this case study, office-based genetic testing was utilized to identify the presence of variants in nearly 80 genes that have been linked to obesity in a patient who had hyper-responsive weight loss results on phentermine/topiramate pharmacotherapy.
RESULTS
A variant of the PLXNA4 gene, which has known pathogenic variants linked to genetic obesity syndromes, was identified in this patient who had a superior weight loss response to phentermine/topiramate pharmacotherapy.
CONCLUSION
Due to overlapping molecular pathways, it is possible that PLXNA4 variants convey a superior weight-loss response and therefore superior cardiovascular risk factor reduction phentermine/topiramate therapy. Further studies are needed to examine the relationship between PLXNA4 variants and weight loss with phentermine/topiramate pharmacotherapy.
PubMed: 37990741
DOI: 10.1016/j.obpill.2023.100059 -
Obesity Pillars Dec 2022/Objectives: Obesity is a risk factor for COVID-19 infection severity and mortality. Anti-obesity medications (AOM) are effective for weight loss. However, weight loss...
BACKGROUND
/Objectives: Obesity is a risk factor for COVID-19 infection severity and mortality. Anti-obesity medications (AOM) are effective for weight loss. However, weight loss outcomes with AOM during the COVID-19 pandemic are yet to be described.
SUBJECTS
/Methods: Between January 1, 2016, and June 30, 2021, a total of 966 patients were prescribed long-term FDA-approved AOMs at the Mayo Clinic. From these patients, 711 patients did not meet inclusion criteria. A total of 255 patients were included.
INTERVENTIONS/METHODS
We performed a retrospective systematic review of electronic medical records and included patients who started a long-term FDA-approved AOM. We excluded patients with history of bariatric procedure, AOM prescription with lorcaserin, orlistat, semaglutide (approved for weight loss after the pandemic), or phentermine (short-term AOM), those taking ≥2 AOMs, <3 months of prescribed AOM, and/or pregnancy. Analysis was divided by 1)preCOVID-19: those who started an AOM before COVID-19 restrictions, 2)COVID-19: those who started an AOM during first quarter of 2020 after the establishment of COVID-19 restrictions. Our primary endpoint was the total body weight loss percentage (%TBWL) at 3, 6, and 12 months after AOM initiation.
RESULTS
There was a statistical difference in TBWL% between the preCOVID-19 and COVID-19 group: 5.3 ± 3.5% vs 4 ± 3.0% (95% CI -2.4 to -0.2; p = 0.02) and 9.7 ± 7.2% vs 6.2 ± 4.7% (95% CI -5.7 to -1.3; p = 0.002) at 3 and 12 months, respectively. At 6 months, the TBWL% was 7.1 for the preCOVID-19 group compared to 6.2% for the COVID-19 (95% CI -2.5 to 0.7; p = 0.25).
CONCLUSION
With the possible exception of liraglutide, this study shows that weight loss outcomes to AOMs were inferior when prescribed during the routine clinical practice throughout COVID-19 pandemic, compared to the outcomes observed prior to the COVID-19 pandemic.
PubMed: 37990666
DOI: 10.1016/j.obpill.2022.100046 -
Biomedicine & Pharmacotherapy =... Dec 2023Intracranial self-stimulation (ICSS) of the medial forebrain bundle in mice is an experimental model use to assess the relative potential of reward-seeking behaviors....
Abused drug-induced intracranial self-stimulation is correlated with the alteration of dopamine transporter availability in the medial prefrontal cortex and nucleus accumbens of mice.
Intracranial self-stimulation (ICSS) of the medial forebrain bundle in mice is an experimental model use to assess the relative potential of reward-seeking behaviors. Here, we used the ICSS model to evaluate the abuse potential of 18 abused drugs: 3-Fluoroethamphetamine (3-FEA); methylphenidate; cocaine; dextroamphetamine; alpha-Pyrrolidinobutyrophenone (α-PBT); 4'-Fluoro-4-methylaminorex (4-FPO); methamphetamine; larocaine; phentermine; paramethoxymethamphetamine (PMMA); phendimetrazine; N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48); Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (CB-13); 4-Ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210); Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018); N-(ortho-methoxybenzyl)-4-ethylamphetamine (4-EA-NBOMe); N-[(2-Methoxyphenyl)methyl]-N-methyl-1-(4-methylphenyl)propan-2-amine (4-MMA-NBOMe); and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine (4-MeO-PCP). We determined dopamine transporter (DAT) availability in the medial prefrontal cortex (mPFC), striatum, and nucleus accumbens (NAc) after drug treatment. DAT availability in the mPFC and NAc significantly correlated with the ICSS threshold after drug treatment. Extracellular dopamine and calcium levels in PC-12 cells were measured following drug treatment. After drug treatment, Spearman rank and Pearson correlation analyses showed a significant difference between the extracellular dopamine level and the ICSS threshold. After drug treatment, Spearman rank correlation analysis showed a significant correlation between Ca signaling and the ICSS threshold. A positive correlation exists between the ICSS threshold and DAT availability in the mPFC and NAc provoked by abused drugs. The relative potential of drug-induced reward-seeking behavior may be related to DAT availability-mediated extracellular dopamine levels in the mPFC and NAc.
Topics: Animals; Mice; Dopamine; Dopamine Plasma Membrane Transport Proteins; Nucleus Accumbens; Prefrontal Cortex; Self Stimulation
PubMed: 37948992
DOI: 10.1016/j.biopha.2023.115860 -
JCEM Case Reports Jan 2023Obesity is a multifactorial chronic disease for which treatment remains challenging. While the cornerstone treatment is lifestyle modification, the addition of...
Obesity is a multifactorial chronic disease for which treatment remains challenging. While the cornerstone treatment is lifestyle modification, the addition of anti-obesity medications leads to greater weight reduction. In cases where monotherapy with a single anti-obesity medication results in either weight stabilization or only modest weight reduction, combination regimens can be highly effective, especially those including glucagon-like peptide-1 receptor agonists. We report the case of a 23-year-old male initially presenting with a body mass index of 84.3 kg/m. In addition to lifestyle modification therapy, he was started on phentermine, topiramate, and metformin, which only resulted in weight stabilization after 1 year. Subsequently, semaglutide (a glucagon-like peptide-1 receptor agonist) was added, along with a lower calorie diet, which resulted in a 32.5% total body weight reduction, approximating that which can be achieved following metabolic/bariatric surgery. This case highlights the potential benefit of combination anti-obesity medication regimens including glucagon-like peptide-1 receptor agonists, as such regimens may provide a synergistic effect by targeting multiple eating behavior pathways simultaneously. Further studies are needed to evaluate the efficacy of combination anti-obesity medication regimens, especially among those achieving suboptimal response to monotherapies.
PubMed: 37908264
DOI: 10.1210/jcemcr/luac038 -
South African Medical Journal =... Aug 2023Phentermine is an internationally recognised amphetamine derivative with significant appetite-suppressing properties. The drug is indicated for the short-term management...
BACKGROUND
Phentermine is an internationally recognised amphetamine derivative with significant appetite-suppressing properties. The drug is indicated for the short-term management of obesity, as the long-term (LT) use of phentermine may potentially be associated with severe cardiovascular side-effects, abuse and dependence. The LT use hereinafter describes periods exceeding 12 consecutive weeks. This use may also be associated with potential drug-drug interactions (PDDIs), which may result in adverse drug reactions (ADRs). The literature reports that phentermine is often prescribed LT and for several other off-label indications, increasing the risk for individuals to experience adverse drug events (ADEs) and drug-drug interactions (DDIs). There are, to our knowledge, no South African (SA) studies investigating the prevalence of co-prescribing LT phentermine with drugs that may potentially cause DDIs.
OBJECTIVE
To determine the prevalence of mild, moderate and severe DDIs with phentermine use when the duration of therapy in private healthcare exceeded 12 consecutive weeks.
METHODS
A cross-sectional drug utilisation review (DUR) was done by using data obtained from a SA pharmacy benefit management (PBM) company's database. Retrospective data of medicine claims for phentermine, from 1 January 2015 to 31 December 2019, were extracted for analysis. The number of days phentermine was supplied was used to identify the study population, in other words, those patients who received the drug LT. A drug interaction checker (Drugs.com) was used to identify potential mild, moderate and severe DDIs when using phentermine and co-prescribed drugs concurrently.
RESULTS
A total of 889 patients received phentermine LT. The top 20 drugs identified as being frequently co-prescribed in this study population demonstrated no mild PDDI, 15 (75%) moderate PDDIs and 5 (25%) severe PDDIs. The most common co-prescribed drug in the moderate group was dextromethorphan (n=282, 31.72%) and the least co-prescribed was formoterol (n=52, 5.85%). Among the drug group 'severe PDDIs', tramadol (n=416, 46.79%) was most frequently prescribed, whereas phenylpropanolamine (n=69, 7.76%) was the least prescribed to patients in this group.
CONCLUSION
There are patients who receive LT phentermine therapy despite the potential severe consequences that may result. These patients may receive concomitant therapy with phentermine and other pharmaceutical constituents, which may potentially cause DDIs, more specifically, moderate and severe DDIs. As such, these patients are not only confronted with the consequences of DDIs but are also at risk to experience ADRs as the residual effect of PDDIs.
Topics: Humans; Phentermine; Retrospective Studies; Cross-Sectional Studies; South Africa; Drug-Related Side Effects and Adverse Reactions; Drug Interactions
PubMed: 37882119
DOI: 10.7196/SAMJ.2023.v113i8.428 -
JAMA Network Open Oct 2023Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this...
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.
Topics: Humans; Female; Adolescent; Child; Male; Anti-Obesity Agents; Obesity, Morbid; Cost-Benefit Analysis; Orlistat; Topiramate; Liraglutide; Obesity; Phentermine
PubMed: 37824146
DOI: 10.1001/jamanetworkopen.2023.36400 -
Psychiatry Investigation Sep 2023Phentermine 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...
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.
PubMed: 37794661
DOI: 10.30773/pi.2023.0045 -
Romanian Journal of Internal Medicine =... Mar 2024Obesity and overweight are the major risk factors for numerous chronic diseases, including cardiovascular diseases such as heart disease and stroke, which are the... (Review)
Review
Obesity and overweight are the major risk factors for numerous chronic diseases, including cardiovascular diseases such as heart disease and stroke, which are the leading causes of death worldwide. The prevalence of obesity has dramatically risen in both developed and developing countries, making it a significant public health concern and a global crisis. Despite lifestyle modifications being the first-line treatment, the high risk of relapse has led to a growing interest in non-invasive pharmacotherapeutic interventions to achieve and maintain weight loss and reverse the growth of the obesity epidemic. Cardiovascular diseases and cancer account for the highest mortality rates among other comorbidities associated with obesity and overweight. Excess and abnormally deposited adipose tissue secretes various inflammatory mediators, leading to cardiovascular diseases and cancers. Weight loss of 5-10% significantly reduces cardiometabolic risk. Medications currently approved in the USA for long-term management of obesity are orlistat, naltrexone, bupropion, phentermine/topiramate, and Glucagon Like Peptide-1 (GLP-1) agonists such as liraglutide and semaglutide. The benefit-to-risk of medications, comorbidities, and individual responses should guide the treatment decisions. The article provides a comprehensive overview and discussion of several weight loss medications used previously and currently, including their efficacy, mechanisms of action, and side effects.
Topics: Humans; Overweight; Cardiovascular Diseases; Obesity; Anti-Obesity Agents; Weight Loss
PubMed: 37752761
DOI: 10.2478/rjim-2023-0023 -
Saudi Pharmaceutical Journal : SPJ :... Oct 2023Recently, 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... (Review)
Review
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.
PubMed: 37712012
DOI: 10.1016/j.jsps.2023.101757 -
Journal of Global Health Sep 2023Despite rising concerns regarding the safety of anti-obesity medications, there is a lack of comprehensive pharmacovigilance investigations utilising real-world data. We...
INTRODUCTION
Despite rising concerns regarding the safety of anti-obesity medications, there is a lack of comprehensive pharmacovigilance investigations utilising real-world data. We aimed to characterise the prevalence and seriousness of adverse drug events (ADEs) related to anti-obesity medications and to identify predictors associated with increased risk of serious adverse events (SAE), thereby conveying evidence on drug safety.
METHODS
We conducted a cross-sectional analysis on ADE cases spontaneously reported to the Korea Adverse Event Reporting System Database (KIDS-KD). ADE reports pertaining to anti-obesity medications prescribed for overweight, obesity (International Classification of Disease, 10th revision (ICD-10) code E66) and abnormal weight gain (ICD-10 code E63.5) were included in the analysis. We performed a disproportionality to detect the association of the system organ class-based ADEs with their seriousness an individual's sex by estimating reporting odds ratios (RORs) and their 95% confidence intervals (CIs). We performed logistic regression to investigate factors that are substantially associated with increased SAE risks by estimating odds ratio (OR) and their 95% CIs.
RESULTS
The most common causative anti-obesity medication was phentermine, followed by liraglutide. ADEs associated with psychiatric disorders (ROR = 1.734; 95% CI = 1.111-2.707), liver and biliary system disorders (ROR = 22.948; 95% CI = 6.613-70.635), cardiovascular disorders (ROR = 5.707; 95% CI = 1.965-16.574), and respiratory disorders (ROR = 4.567; 95% CI = 1.774-11.762) were more likely to be serious events. Additionally, men are more likely to experience ADEs related gastrointestinal disorders (ROR = 1.411) and less likely to have heart and rhythm disorders (ROR = 0.507). The risk of SAE incidences was positively correlated with being male (OR = 2.196; 95% CI = 1.296-3.721), dual or triple combination of anti-obesity medications (OR = 3.258; 95% CI = 1.633-6.501 and OR = 8.226; 95% CI = 3.046-22.218, respectively), and concomitant administration of fluoxetine (OR = 5.236; 95% CI = 2.218-12.365).
CONCLUSIONS
Seriousness of anti-obesity medication-related ADEs differs among system-organ class, while sex-related differences in ADE profiles are also present. The predictors substantially increasing risk of SAE incidences include being male, having a higher number of concomitant medications (including multiple combination of anti-obesity medications), and concurrent use of fluoxetine. Nonetheless, further pharmacovigilance investigation and monitoring are needed to enhance awareness on ADEs induced by anti-obesity medications.
Topics: Humans; Male; Female; Cross-Sectional Studies; Fluoxetine; Pharmacovigilance; Obesity; Cardiovascular Diseases
PubMed: 37651636
DOI: 10.7189/jogh.13.04095