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Journal of Analytical Toxicology Jun 2024Brain can a useful specimen for toxicology testing as it is a protected and isolated organ with lower metabolic activity than other tissues, but there is currently no...
Brain can a useful specimen for toxicology testing as it is a protected and isolated organ with lower metabolic activity than other tissues, but there is currently no published data supporting the stability of stimulant drugs in prepared brain homogenates. Brain homogenates were evaluated to determine the stability of the following stimulant drugs: amphetamine, benzoylecgonine, bupropion, cocaethylene, cocaine, ephedrine, methylenedioxyamphetamine, methylenedioxymethamphetamine, methamphetamine, and phentermine. Four different homogenates were prepared at a 1:4 dilution with deionized water and fortified at 500 ng/mL of: cocaine without sodium fluoride, cocaine with 1% sodium fluoride, stimulant drugs other than cocaine without sodium fluoride, and stimulant drugs other than cocaine with 1% sodium fluoride. The fortified homogenates were aliquoted into 13x100 mm screw cap tubes and stored at room temperature (~20 °C), refrigerated (2-8 °C), or frozen (< -5 °C) and analyzed in triplicate on Days 0, 1, 3, 7, 14, 30, 60, and 90. Analytes were considered stable as long as the difference in analyte/internal standard response ratio from Day 0 was less than 20% and the peaks met qualitative acceptance criteria. All analytes were stable for up to 90 days when stored frozen with or without sodium fluoride and had variable stability at all other evaluated conditions.
PubMed: 38937871
DOI: 10.1093/jat/bkae058 -
Diabetes, Obesity & Metabolism Jun 2024To compare the incidence of adverse events (AEs) related to antiobesity medications (AOMs; glucagon-like peptide-1 receptor agonists [GLP-1RAs] vs. non-GLP-1RAs) after...
AIM
To compare the incidence of adverse events (AEs) related to antiobesity medications (AOMs; glucagon-like peptide-1 receptor agonists [GLP-1RAs] vs. non-GLP-1RAs) after bariatric surgery.
METHODS
This single-centre retrospective cohort included patients (aged 16-65 years) who had undergone laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy (cohort entry date) and initiated AOMs. Participants were categorized as users of US Food and Drug Administration (FDA)-approved, off-label, or GLP-1RA AOMs if documented as receiving the medication on or after cohort entry date. Non-GLP-1RA AOMs were phentermine, orlistat, topiramate, canagliflozin, dapagliflozin, empagliflozin, naltrexone, bupropion/naltrexone and phentermine/topiramate. GLP-1RA AOMs included: semaglutide, dulaglutide, exenatide and liraglutide. The primary outcome was AE incidence. Logistic regression was used to determine the association of AOM exposure with AEs.
RESULTS
We identified 599 patients meeting our inclusion criteria, 83% of whom were female. Their median (interquartile range [IQR]) age was 47.8 (40.9-55.4) years. The median duration of surgery to AOM exposure was 30 months. GLP-1RAs use was not associated with higher odds of AEs: adjusted odds ratio (aOR) 1.1 (95% confidence interval [CI] 0.5-2.6) and aOR 1.1 (95% CI 0.6-2.3) for GLP-1RA versus FDA-approved and off-label AOM use, respectively. AOM initiation ≥12 months after surgery was associated with lower risk of AEs compared to <12 months (aOR 0.01 [95% CI 0.0-0.01]; p < 0.001).
CONCLUSION
Our results showed that GLP-1RA AOMs were not associated with an increased risk of AEs compared to non-GLP-1RA AOMs in patients who had previously undergone bariatric surgery. Prospective studies are needed to identify the optimal timeframe for GLP-1RA initiation.
PubMed: 38934217
DOI: 10.1111/dom.15737 -
JAMA Jun 2024Body mass index (BMI) of the 95th or greater percentile for age and sex is common among young people, and its prevalence has increased in recent decades.
IMPORTANCE
Body mass index (BMI) of the 95th or greater percentile for age and sex is common among young people, and its prevalence has increased in recent decades.
OBJECTIVE
To examine the benefits and harms of weight management interventions initiated in health care settings among children and adolescents with high BMI.
DATA SOURCES
MEDLINE via Ovid, PsycINFO via Ovid, and the Cochrane Central Registry of Controlled Trials through January 12, 2023; ongoing surveillance through January 26, 2024.
STUDY SELECTION
English-language studies of weight management interventions (behavioral and pharmacologic, including liraglutide, semaglutide, orlistat, and phentermine/topiramate) among children aged 2 to 18 years with high BMI (eg, ≥85th or ≥95th percentile for age and sex) conducted in or recruited from health care settings.
DATA EXTRACTION AND SYNTHESIS
One investigator abstracted data; a second checked for accuracy. Outcomes with sufficient evidence for meta-analysis were pooled using random-effects models.
MAIN OUTCOMES AND MEASURES
BMI and other weight-related outcomes, cardiometabolic measures, quality of life, physical activity, dietary pattern scores, and harms.
RESULTS
Fifty-eight randomized clinical trials (RCTs) were included (N = 10 143). Behavioral interventions were associated with small reductions in BMI and other weight outcomes after 6 to 12 months (28 RCTs [n = 4494]; mean difference in change between groups, -0.7 [95% CI, -1.0 to -0.3]). Larger effects were seen in interventions with higher contact hours and that offered physical activity sessions. Reporting was sparse for outcomes other than BMI, with few significant findings. Semaglutide and phentermine/topiramate had the largest effects on BMI (eg, 1 RCT [n = 201] for semaglutide; mean difference, -6.0 [95% CI, -7.3 to -4.6]). The very few studies that evaluated outcomes after medication discontinuation showed immediate weight regain. Gastrointestinal adverse effects were common with liraglutide, semaglutide, and orlistat. Serious adverse effects were rare, but no studies had follow-up longer than 17 months.
CONCLUSIONS AND RELEVANCE
In the short term, weight management interventions led to lower BMI in children and adolescents, with no evidence of serious harm. Evidence is lacking about how weight management interventions affect BMI beyond 1 year and after medication discontinuation and about longer-term effects on other outcomes.
PubMed: 38888913
DOI: 10.1001/jama.2024.6739 -
Pediatric Obesity Jun 2024Anti-obesity medications (AOMs) are promising lifestyle modification (LSM) adjuncts for obesity treatment, and phentermine is commonly prescribed in paediatric weight...
BACKGROUND
Anti-obesity medications (AOMs) are promising lifestyle modification (LSM) adjuncts for obesity treatment, and phentermine is commonly prescribed in paediatric weight management clinics. Determining 'real-world' AOM effectiveness and characteristics predicting response is important.
OBJECTIVES
We sought to describe phentermine plus LSM effectiveness and identify baseline characteristics predicting response.
METHODS
This was a retrospective cohort study among youth seen in a US academic-based weight management clinic from 2012 to 2020. Baseline characteristics (e.g., body mass index (BMI), liver transaminases, eating-related behaviours) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, %BMI change, weight) were determined through electronic health records and intake surveys.
RESULTS
Among 91 youth prescribed phentermine plus LSM over 8 years (mean %BMIp95 150%), %BMIp95 was statistically significantly reduced at 1.5, 3, 6 and 12 months (peak reduction 10.9 percentage points at 6 months; p < 0.001). Considering multiple comparisons, the presence of baseline elevated alanine aminotransferase was associated with statistically significant smaller 1.5-month %BMIp95 reductions (p = 0.001) and higher food responsiveness with smaller 3- (p = 0.001) and 6-month (p < 0.001) reductions.
CONCLUSIONS
Phentermine plus LSM reduced %BMIp95 among youth in a weight management clinic, and baseline characteristics may help determine those more or less likely to respond. Prospective studies are needed to further characterize effectiveness and confirm response predictors.
PubMed: 38886982
DOI: 10.1111/ijpo.13143 -
American Journal of Ophthalmology Case... Sep 2024This report describes the presentation of a 49-year-old woman with a branch retinal artery occlusion of the right eye in the setting of taking phentermine, a commonly...
PURPOSE
This report describes the presentation of a 49-year-old woman with a branch retinal artery occlusion of the right eye in the setting of taking phentermine, a commonly used weight loss medication.
OBSERVATIONS
A 49-year-old woman presented with acute painless vision loss in her right eye and was found to have a branch retinal artery occlusion after taking prescribed dosages of phentermine for weight loss therapy. Fundus examination revealed retinal whitening in the distribution of the superior temporal branch retinal artery, and spectral domain optical coherence tomography demonstrated macular edema. Systemic evaluation was negative for cardiovascular, infectious, or autoimmune etiologies. Based on the retinal findings, the patient was diagnosed with phentermine associated branch retinal artery occlusion. She was followed for nine years with no further complications and her vision remained stable in the right eye.
CONCLUSIONS AND IMPORTANCE
This case highlights that phentermine, a commonly used weight loss medication, could be associated with ischemic retinopathies. Thus, clinicians should be aware that retinal vascular occlusions may not only occur in those who use recreational amphetamines but also in patients taking the prescribed dosages of a weight loss medication like phentermine.
PubMed: 38884112
DOI: 10.1016/j.ajoc.2024.102013 -
ACG Case Reports Journal Jun 2024Phentermine is an amine anorectic that acts as a sympathomimetic agent and undergoes hepatic metabolism predominantly through CYP3A4. It is commonly used as a mediation...
Phentermine is an amine anorectic that acts as a sympathomimetic agent and undergoes hepatic metabolism predominantly through CYP3A4. It is commonly used as a mediation to facilitate weight loss. Side effects of phentermine can include pulmonary hypertension, valvular heart disease, palpitations, increased heart rate or blood pressure, diarrhea, and cognitive impairment. Very rarely, phentermine usage has been associated with causing ischemic colitis. The mechanism of action for ischemic colitis from phentermine is not well defined but will be discussed in this review. We present a case of a woman who used phentermine daily for weight loss and was endoscopically confirmed to have ischemic colitis after presenting with abdominal pain and bloody diarrhea.
PubMed: 38841705
DOI: 10.14309/crj.0000000000001363 -
Current Opinion in Pediatrics May 2024The purpose of this review is to describe the existing limited data related to the use of semaglutide in adolescents with obesity, supplementing with findings from adult...
PURPOSE OF REVIEW
The purpose of this review is to describe the existing limited data related to the use of semaglutide in adolescents with obesity, supplementing with findings from adult studies of semaglutide use.
RECENT FINDINGS
Semaglutide, as a once weekly subcutaneous injection for weight management, effectively reduces body mass index (BMI) while improving hyperglycemia, elevated alanine aminotransferase levels, hyperlipidemia, and quality of life in youth with obesity. As of this review, only one large randomized clinical trial of semaglutide in youth has been completed, with a follow-up duration of 68 weeks. Thus, long-term data on the safety in adolescents is limited, particularly regarding the risks of cholelithiasis, pancreatitis, suicidal ideation, and disordered eating. Due to the cost of semaglutide, particularly in the United States, limited cost effectiveness analyses have demonstrated unfavorable incremental cost-effectiveness ratios for semaglutide relative to phentermine-topiramate as an alternative antiobesity medication in adolescents.
SUMMARY
Semaglutide represents an important advance in the pediatric obesity management, with clear short-term reductions in BMI and improvement in metabolic parameters. However, its long-term safety and efficacy for youth with obesity remain to be demonstrated. Additional research is needed to assess trends in utilization and adherence to minimize the risk of worsening socioeconomic disparities in pediatric obesity.
PubMed: 38774967
DOI: 10.1097/MOP.0000000000001365 -
Journal of Pharmaceutical and... Aug 2024As the adulteration of dietary supplements with synthetic drugs remains a prevalent issue, the inclusion of anti-obesity agents may pose health risks, potentially...
As the adulteration of dietary supplements with synthetic drugs remains a prevalent issue, the inclusion of anti-obesity agents may pose health risks, potentially leading to central nervous system or cardiovascular diseases. However, surveillance studies on the use of anti-obesity agents by the Chinese population are limited. This study aims to establish an efficient and rapid hair pretreatment method using dispersive liquid-liquid microextraction (DLLME) combined with high-speed grinding and develop a sensitive and accurate analytical method employing ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for detecting 13 potential anti-obesity agents in hair samples. Herein, hair samples were washed sequentially with 0.1% sodium dodecyl sulfate (SDS), water and acetone, and then ground at high speed using 1 mL of an extraction solution (internal standard solution-n-butanol-1.2 mol/L NaHPO, pH10.0, 100:400:500, v/v/v for procaterol; internal standard solution-ethyl acetate-1.2 mol/L NaHPO, pH8.0, 100:300:600, v/v/v for other 12 anti-obesity agents) while simultaneously performing DLLME. The developed method successfully detected 13 anti-obesity agents within 11 min, including bambuterol, clenbuterol, ractopamine, clorprenaline, formoterol, salbutamol, terbutaline, procaterol, phentermine, bupropion, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine, which improved the screening efficiency. The calibration curves exhibited good linearity of 0.025-5 ng/mg, achieving correlation coefficients of r ≥ 0.99. The lower limits of quantification (LLOQs) for the analytes were 0.025 ng/mg, demonstrating acceptable levels of accuracy and precision. Recovery rates ranged between 73.30% and 107.47% across the three concentrations of 0.075, 0.375, and 3.75 ng/mg. The validated method was successfully applied to 369 real cases and detected six analytes, including bambuterol, salbutamol, terbutaline, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine. This method offers several advantages, including simple pretreatment, high extraction efficiency, rapid extraction, solvent economy, and pollution mitigation, making it highly suitable for large-scale surveillance of usage of added anti-obesity agents.
Topics: Tandem Mass Spectrometry; Anti-Obesity Agents; Liquid Phase Microextraction; Chromatography, High Pressure Liquid; Hair; Humans; Limit of Detection; Reproducibility of Results
PubMed: 38772203
DOI: 10.1016/j.jpba.2024.116236 -
Urology Case Reports May 2024Uric acid is one of the few kidney stone minerals that can dissolve using oral alkalinization therapies such as potassium citrate. We report an obese female whose...
Uric acid is one of the few kidney stone minerals that can dissolve using oral alkalinization therapies such as potassium citrate. We report an obese female whose recalcitrant uric acid stones were eliminated using the weight loss medication phentermine/topiramate (Qsymia), a metabolic stimulant and carbonic anhydrase inhibitor. Pre- and post-dissolution 24-h urine studies and computed tomography images are included with a proposed mechanism of action of this medication. This is the first description of a non-alkaline oral therapy used alone for uric acid stone dissolution. Additional investigation of this medication in obese or diabetic uric acid stone formers is warranted.
PubMed: 38756527
DOI: 10.1016/j.eucr.2024.102748