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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 -
Saudi Journal of Gastroenterology :... May 2024Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common cause of chronic hepatitis in adult and pediatric patients. Adolescents with severe...
BACKGROUND
Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common cause of chronic hepatitis in adult and pediatric patients. Adolescents with severe MASLD can demonstrate a more aggressive disease phenotype as they more commonly develop liver fibrosis than BMI matched adults. Therefore, MASLD is the fastest growing indication for liver transplants in young adults.
METHODS
Pioglitazone has been shown to improve liver histology in adult patients with MASLD, and in some studies, it attenuated liver fibrosis. Despite its perceived efficacy, pioglitazone is not widely used, likely due to its side effect profile, specifically increased weight gain. Topiramate lowers body weight in adolescents and in combination with phentermine, is one of the few FDA-approved medications for the management of obesity in children over 12 years of age. We performed a retrospective review of the outcomes in pediatric patients with severe MASLD, treated with the combined pioglitazone and topiramate therapy.
RESULTS
Here, we report a case series of seven adolescents with severe MASLD and ≥F2 liver fibrosis treated with the combined pioglitazone and topiramate therapy. The combined therapy improved mean serum ALT from 165 ± 80 U/L to 89 ± 62 U/L after 12 months mean duration of treatment. One patient who completed 24 months of the combined therapy demonstrated a decrease in liver stiffness from 8.9 kPa to 5.6 kPa, as assessed by FibroScan elastography. There was a significant increase in body weight during this time, however, body mass index as a percentage of the 95th percentile adjusted for age and gender did not increase significantly, 151 ± 29% vs. 152 ± 28%. Moreover, waist circumference, mid-upper arm circumference, percent body fat, and muscle mass were not significantly different before and after treatment. Serum lipid levels and hemoglobin A1c also did not change with the treatment.
CONCLUSION
In summary, this case series provides encouraging results about the efficacy of the combined pioglitazone and topiramate therapy for the management of adolescents with severe MASLD, which should be further explored in clinical studies.
PubMed: 38726916
DOI: 10.4103/sjg.sjg_428_23 -
Ophthalmology. Glaucoma Apr 2024To identify and quantify medications causing angle-closure glaucoma through the FDA Adverse Event Reporting System (FAERS).
OBJECTIVE
To identify and quantify medications causing angle-closure glaucoma through the FDA Adverse Event Reporting System (FAERS).
DESIGN
National retrospective database analysis.
SUBJECTS
There were 11 737 133 total adverse event reports from the FDA Federal Adverse Event Reporting System (FAERS) database 2004 to third quarter of 2023 (2023Q3), which included 1629 reports of angle-closure glaucoma.
METHODS
Drugs associated with reports of angle-closure glaucoma were identified in FAERS through disproportionality analysis MAIN OUTCOME MEASURES: To ascertain if these reports yielded statistically significant signals, we used the proportional reporting ratio (PRR), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC). We considered a signal to be detected when all 4 disproportionality analysis metrics were positive.
RESULTS
We identified a total of 1629 adverse event reports linked to 611 suspected drugs over the course of 20 years (2004-2023Q3). Frequently reported drugs included topiramate (520 reports) and citalopram (69 reports), amongst many others. Eighteen medications yielded a positive signal, including lesser-known medications like olanzapine, phentermine, and ranibizumab. Tropicamide exhibited the most robust statistical significance (n = 18; PRR: 164.263; ROR [95% confidence interval {CI}]: 167.95 [104.994-268.655]; EBGM [EBGM05]: 162.421 [109.5]; IC [IC05]: 7.344 [4.591]), while acetazolamide was the second strongest (n = 51; PRR: 113.088; ROR 95% CI: 114.782 [86.665-152.021]; EBGM [EBGM05]: 109.506 [86.501]; IC [IC05]: 6.775 [5.115]).
CONCLUSIONS
Drug-induced glaucoma included both well-known medications such as topiramate as well as lesser-known medications such as olanzapine, phentermine, and ranibizumab. Clinician awareness of these findings is important.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38679326
DOI: 10.1016/j.ogla.2024.04.006 -
PloS One 2024Obesity is a major global health epidemic that has adverse effects on both the people affected as well as the cost to society. Several anti-obesity drugs that target...
Obesity is a major global health epidemic that has adverse effects on both the people affected as well as the cost to society. Several anti-obesity drugs that target GLP-1 receptors have recently come to the market. Here, we describe the effects of tesofensine, a novel anti-obesity drug that acts as a triple monoamine neurotransmitter reuptake inhibitor. Using various techniques, we investigated its effects on weight loss and underlying neuronal mechanisms in mice and rats. These include behavioral tasks, DeepLabCut videotaped analysis, electrophysiological ensemble recordings, optogenetic activation, and chemogenetic silencing of GABAergic neurons in the Lateral Hypothalamus (LH). We found that tesofensine induces a greater weight loss in obese rats than lean rats, while differentially modulating the neuronal ensembles and population activity in LH. In Vgat-ChR2 and Vgat-IRES-cre transgenic mice, we found for the first time that tesofensine inhibited a subset of LH GABAergic neurons, reducing their ability to promote feeding behavior, and chemogenetically silencing them enhanced tesofensine's food-suppressing effects. Unlike phentermine, a dopaminergic appetite suppressant, tesofensine causes few, if any, head-weaving stereotypy at therapeutic doses. Most importantly, we found that tesofensine prolonged the weight loss induced by 5-HTP, a serotonin precursor, and blocked the body weight rebound that often occurs after weight loss. Behavioral studies on rats with the tastant sucrose indicated that tesofensine's appetite suppressant effects are independent of taste aversion and do not directly affect the perception of sweetness or palatability of sucrose. In summary, our data provide new insights into the effects of tesofensine on weight loss and the underlying neuronal mechanisms, suggesting that tesofensine may be an effective treatment for obesity and that it may be a valuable adjunct to other appetite suppressants to prevent body weight rebound.
Topics: Animals; GABAergic Neurons; Rats; Mice; Anti-Obesity Agents; Male; Obesity; Feeding Behavior; Hypothalamic Area, Lateral; Hypothalamus; Mice, Transgenic; Weight Loss; Rats, Sprague-Dawley; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 38656972
DOI: 10.1371/journal.pone.0300544 -
Therapeutic Advances in Neurological... 2024Several studies have demonstrated that early childhood and adolescent obesity are risk factors for multiple sclerosis (MS) susceptibility. Obesity is thought to share...
BACKGROUND
Several studies have demonstrated that early childhood and adolescent obesity are risk factors for multiple sclerosis (MS) susceptibility. Obesity is thought to share inflammatory components with MS through overproduction of pro-inflammatory adipokines (e.g., leptin) and reduction of anti-inflammatory adipokines (e.g, adiponectin). Recently, drug repurposing (i.e. identifying new indications for existing drugs) has garnered significant attention. The US Food and Drug Administration Adverse Event Reporting System (FAERS) database serves not only as a resource for mining adverse drug reactions and safety signals but also for identifying inverse associations and potential medication repurposing opportunities.
OBJECTIVE
We aimed to explore the association between weight-loss-inducing drugs and MS using real-world reports from the FAERS database.
DESIGN
Secondary analysis of existing data from the FAERS database.
METHODS
We conducted a disproportionality analysis using the FAERS database between the fourth quarter of 2003 and the second quarter of 2023 to explore associations between MS and weight loss-inducing drugs. Disproportionality was quantified using the reporting odds ratio (ROR). An inverse association was defined when the upper limit of the 95% confidence interval for ROR was <1.
RESULTS
We found an inverse association between MS and anti-diabetic weight loss-inducing drugs including semaglutide (ROR: 0.238; 95% CI: 0.132-0.429), dulaglutide (ROR: 0.165; 95% CI: 0.109-0.248), liraglutide (ROR: 0.161; 95% CI: 0.091-0.284), empagliflozin (ROR: 0.234; 95% CI: 0.146-0.377), and metformin (ROR: 0.387; 95% CI: 0.340-0.440). No inverse associations were found for other weight loss-inducing drugs such as phentermine, bupropion, topiramate, zonisamide, and amphetamine. An exception was naltrexone (ROR: 0.556; 95% CI: 0.384-0.806).
CONCLUSION
Our findings suggest a potential consideration for repurposing anti-diabetic weight loss-inducing drugs including semaglutide, dulaglutide, and liraglutide (glucagon-like peptide-1 receptor agonists), empagliflozin (sodium-glucose cotransporter-2 inhibitor), and metformin (biguanide), for MS. This warrants validation through rigorous methodologies and prospective studies.
PubMed: 38566910
DOI: 10.1177/17562864241241383 -
Drug Design, Development and Therapy 2024Anti-obesity medications (AOMs), along with lifestyle interventions, are effective means of inducing and maintaining weight loss in patients with obesity. Although the...
PURPOSE
Anti-obesity medications (AOMs), along with lifestyle interventions, are effective means of inducing and maintaining weight loss in patients with obesity. Although the efficacy of AOMs has been reported, there have been no direct comparisons of these drugs. Therefore, in the present study, we aimed to compare the efficacy of all the AOMs available in Korea in a real-world setting.
PATIENTS AND METHODS
The body weight and composition of 205 adults treated with phentermine, phentermine/topiramate, liraglutide, naltrexone/bupropion, lorcaserin, or orlistat for at least 6 months were analyzed at 2 month intervals. The prevalence of the achievement of a ≥5% weight loss and the changes in body composition were compared between participants using each AOM at each visit.
RESULTS
A total of 132 (64.4%) participants achieved ≥5% weight loss within 6 months (prevalence of ≥5% weight loss after 6 months: phentermine, 87.2%; phentermine/topiramate, 67.7%; liraglutide, 58.1%; naltrexone/bupropion, 35.3%; lorcaserin, 75%; orlistat, 50%). At each visit, after adjustment for age, sex, and baseline body weight, phentermine use was associated with a significantly higher prevalence of ≥5% weight loss than the use of the other AOMs, except for liraglutide. There were significant differences in the body weight, body mass index and body fat mass among the AOM groups by visit (P for interaction <0.05), but not in their waist circumference, skeletal muscle mass, percentage body fat, or visceral fat area.
CONCLUSION
All the AOMs were effective at inducing and maintaining weight loss, in the absence of significant changes in muscle mass, over a 6 month period, and the short-term use of phentermine and the long-term use of phentermine/topiramate or liraglutide would be practical choices for the treatment of obesity. However, further, large-scale studies are necessary to confirm these findings.
Topics: Adult; Humans; Orlistat; Topiramate; Liraglutide; Naltrexone; Bupropion; Fructose; Anti-Obesity Agents; Obesity; Body Weight; Phentermine; Weight Loss
PubMed: 38524878
DOI: 10.2147/DDDT.S445415 -
The Korean Journal of Gastroenterology... Mar 2024The prevalence of obesity with various complications is increasing rapidly in Korea. Although lifestyle modification is fundamental in obesity treatment, more effective... (Review)
Review
The prevalence of obesity with various complications is increasing rapidly in Korea. Although lifestyle modification is fundamental in obesity treatment, more effective treatment tools are required. Many advances in obesity treatment have been reported recently, including lifestyle modifications and pharmacological, endoscopic, and surgical treatments. Drugs with proven long-term efficacy and safety are preferred because management for obesity treatment is a long-term process. Currently, four medications are available for long-term use in Korea: Orlistat, Naltrexone/bupuropion NR, Phentermine/topiramate capsule, and Liraglutide. Recently, semaglutide and tirzepatide have been attracting attention because of their effectiveness and convenience, but they are not yet available in Korea. In addition, there are limitations such as the yo-yo effect when discontinuing the drug, long-term safety, and cost. Patients and medical staff must be aware of the advantages and side effects of each medication to ensure the successful treatment of obesity.
Topics: Humans; Anti-Obesity Agents; Phentermine; Obesity; Orlistat; Liraglutide
PubMed: 38522852
DOI: 10.4166/kjg.2024.016 -
Journal of the Endocrine Society Mar 2024Despite a high prevalence of obesity in the veteran population, antiobesity medications (AOMs) have been underused in the Veterans Health Administration. Real-world...
CONTEXT
Despite a high prevalence of obesity in the veteran population, antiobesity medications (AOMs) have been underused in the Veterans Health Administration. Real-world reports on outcomes when AOMs have been used in veterans is limited.
OBJECTIVE
To analyze weight loss outcomes from a local Veterans Health Administration pharmacotherapy-based weight management clinic (WMC).
METHODS
This was a retrospective cohort study of veterans enrolled in a local WMC for 15 months from August 2016 through September 2018 and followed through November 2019. Patients were offered 1 of 5 available AOMs based on their comorbidities. Factors associated with weight loss (5% or more weight loss) were assessed.
KEY RESULTS
A total of 159 patients were seen in a WMC, 149 (93.7%) veterans were prescribed an AOM, and 129 returned for follow-up. Overall, 61/129 (47%) patients achieved 5% or greater weight loss and 28/129 (22%) achieved 10% or greater weight loss within 15 months. Clinically significant weight loss (%) over the first 15 months was achieved with phentermine/topiramate ER (-6.3%) and liraglutide (-7.5%), but not with orlistat (-3.9%) and lorcaserin (-3.6%). Comorbid obstructive sleep apnea was negatively associated with achieving ≥5% weight loss.
CONCLUSION
Phentermine/topiramate ER and liraglutide were found to be effective AOMs among veterans. Further work is needed to mitigate barriers to AOM initiation given the continued rise in obesity.
PubMed: 38515583
DOI: 10.1210/jendso/bvae042 -
BMC Primary Care Mar 2024The prevalence of obesity has been increasing worldwide and is associated with increased risk of morbidity and mortality. Weight management can reduce the risk of...
BACKGROUND
The prevalence of obesity has been increasing worldwide and is associated with increased risk of morbidity and mortality. Weight management can reduce the risk of complications and improve the quality of life of patients with obesity. This study explored primary care physicians' (PCPs') attitudes and knowledge about weight management.
METHODS
An anonymous questionnaire was distributed to 400 PCPs between 2020 and 2021. The survey included questions on treatment approaches (pharmaceutical and surgical) and items regarding the respondents' demographic characteristics. We compared PCPs with low or high proactivity toward weight management. We explored attitudes and knowledge with the chi-square test for categorical variables or the Mann-Whitney test for continuous variables.
RESULTS
A total of 145 PCPs answered our survey (a response rate of 36.25%). More than half (53.8%) of the respondents showed low proactivity toward weight management in their practice. Proactive respondents were more likely to believe that pharmaceutical treatment effectively reduces weight and offered medical and surgical treatment options more frequently to their patients. Lack of knowledge was the most predominant reason for PCPs avoiding offering treatment to their patients, especially in less proactive PCPs (33.3% vs. 5.3%, p-value < 0.001). When comparing different pharmaceutical options, 46.6% of PCPs report they tend to prescribe liraglutide to their patients compared with only 11% who prescribe orlistat and 10.3% who prescribe phentermine (p-value < 0.001).
CONCLUSIONS
Many PCPs still do not actively provide obesity treatment despite improved awareness and therapeutic options. PCPs' proactivity and attitudes are vital to this effort.
Topics: Humans; Cross-Sectional Studies; Physicians, Primary Care; Israel; Quality of Life; Obesity; Pharmaceutical Preparations
PubMed: 38504167
DOI: 10.1186/s12875-024-02324-5 -
The Primary Care Companion For CNS... Feb 2024
Topics: Humans; Bipolar Disorder; Phentermine; Mania; Weight Loss
PubMed: 38395144
DOI: 10.4088/PCC.23cr03624