-
JAMA Network Open Aug 2023Antiobesity pharmacotherapy is recommended for adolescents ages 12 years and older with obesity. Several medications have been approved by the US Food and Drug...
IMPORTANCE
Antiobesity pharmacotherapy is recommended for adolescents ages 12 years and older with obesity. Several medications have been approved by the US Food and Drug Administration for adolescent use, but the most cost-effective medication remains unclear.
OBJECTIVE
To estimate the cost-effectiveness of lifestyle counseling alone and as adjunct to liraglutide, mid-dose phentermine and topiramate (7.5 mg phentermine and 46 mg topiramate), top-dose phentermine and topiramate (15 mg phentermine and 92 mg topiramate), or semaglutide among adolescent patients with obesity.
DESIGN, SETTING, AND PARTICIPANTS
This economic evaluation used a microsimulation model to project health and cost outcomes of lifestyle counseling alone and adjunct to liraglutide, mid-dose phentermine and topiramate, top-dose phentermine and topiramate, or semaglutide over 13 months, 2 years, and 5 years among a hypothetical cohort of 100 000 adolescents with obesity, defined as an initial body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 37. Model inputs were derived from clinical trials, published literature, and national sources. Data were analyzed from April 2022 to July 2023.
EXPOSURES
Lifestyle counseling alone and as adjunct to liraglutide, mid-dose phentermine and topiramate, top-dose phentermine and topiramate, or semaglutide.
MAIN OUTCOMES AND MEASURES
The main outcome was quality-adjusted life years (QALYs), costs (2022 US dollars), and incremental cost-effectiveness ratios (ICERs), with future costs and QALYs discounted 3.0% annually. A strategy was considered cost-effective if the ICER was less than $100 000 per QALY gained. The preferred strategy was determined as the strategy with the greatest increase in QALYs while being cost-effective. One-way and probabilistic sensitivity analyses were used to assess parameter uncertainty.
RESULTS
The model simulated 100 000 adolescents at age 15 with an initial BMI of 37, of whom 58 000 (58%) were female. At 13 months and 2 years, lifestyle counseling was estimated to be the preferred strategy. At 5 years, top-dose phentermine and topiramate was projected to be the preferred strategy with an ICER of $56 876 per QALY gained vs lifestyle counseling. Semaglutide was projected to yield the most QALYs, but with an unfavorable ICER of $1.1 million per QALY gained compared with top-dose phentermine and topiramate. Model results were most sensitive to utility of weight reduction and weight loss of lifestyle counseling and top-dose phentermine and topiramate.
CONCLUSIONS AND RELEVANCE
In this economic evaluation of pharmacotherapy for adolescents with obesity, top-dose phentermine and topiramate as adjunct to lifestyle counseling was estimated to be cost-effective after 5 years. Long-term clinical trials in adolescents are needed to fully evaluate the outcomes of pharmacotherapy, especially into adulthood.
Topics: United States; Adolescent; Humans; Female; Male; Cost-Benefit Analysis; Pediatric Obesity; Topiramate; Liraglutide; Phentermine
PubMed: 37651143
DOI: 10.1001/jamanetworkopen.2023.29178 -
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 -
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 -
Current Obstetrics and Gynecology... Jun 2023This report will review existing literature on weight loss outcomes for various anti-obesity medications (AOMs) as well as their effects on human fertility, pregnancy,...
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.
PubMed: 37427372
DOI: 10.1007/s13669-023-00350-1 -
Journal of Obesity & Metabolic Syndrome Jun 2023Obesity is a prevalent global health issue affecting approximately half of the world's population. Extensive scientific research highlights the urgent need for effective... (Review)
Review
Obesity is a prevalent global health issue affecting approximately half of the world's population. Extensive scientific research highlights the urgent need for effective obesity management to mitigate health risks and prevent complications. While bariatric surgery has proven to be highly effective, providing substantial short-term and long-term weight loss and resolution of obesity-related comorbidities, it is important to recognize its limitations and associated risks. Given the global obesity epidemic and the limitations of surgical interventions, there is high demand for effective and safe anti-obesity medications (AOMs). In Korea, the Korean Society for the Study of Obesity strongly advocates for the use of pharmacotherapy in Korean adults with a body mass index of 25 kg/m or higher who have not achieved weight reduction through non-pharmacological treatments. Currently, five AOMs have been approved for long-term weight management: orlistat, naltrexone/bupropion, phentermine/topiramate, liraglutide, and semaglutide. Tirzepatide is awaiting approval, and combination of semaglutide/cagrilintide and oral semaglutide are currently undergoing rigorous evaluation in phase 3 clinical trials. Furthermore, other promising drugs, including orforglipron, BI 456906, and retartrutide, are progressing to phase 3 studies, expanding the therapeutic options for obesity management. In personalized patient care, physicians play a crucial role in accurately identifying individuals who genuinely require pharmacotherapy and selecting appropriate AOMs based on individual patient characteristics. By integrating evidence-based interventions and considering the unique needs of patients, healthcare professionals significantly contribute to the success of obesity management strategies.
PubMed: 37349257
DOI: 10.7570/jomes23032 -
Diabetes, Metabolic Syndrome and... 2023Obesity 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... (Review)
Review
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.
PubMed: 37337548
DOI: 10.2147/DMSO.S392684 -
Molecules (Basel, Switzerland) Apr 2023Obesity is characterized by the excessive accumulation of fat, which triggers a low-grade chronic inflammatory process. Currently, the search for compounds with...
Obesity is characterized by the excessive accumulation of fat, which triggers a low-grade chronic inflammatory process. Currently, the search for compounds with anti-obesogenic effects that help reduce body weight, as well as associated comorbidities, continues. Among this group of compounds are plant extracts and flavonoids with a great diversity of action mechanisms associated with their beneficial effects, such as anti-inflammatory effects and/or as signaling molecules. In the bark of tree, there are different classes of metabolites with anti-inflammatory properties, such as quercetin. Therefore, the present work studied the effect of the ethanolic extract of and quercetin on the mRNA of inflammation markers in obesity compared to the drugs currently used. Total RNA was extracted from epididymal adipose tissue of high-fat diet-induced obese Wistar rats treated with orlistat, phentermine, extract, and quercetin. The rats treated with and quercetin showed 36 and 31% reductions in body weight compared to the obese control, and they likewise inhibited pro-inflammatory molecules: , , , , , and without modifying the expression of and . Additionally, only overexpressed . Both and quercetin led to a reduction in the expression of pro-inflammatory genes, modifying signaling pathways, which led to the regulation of the obesity-inflammation state.
Topics: Rats; Animals; Anti-Obesity Agents; Rats, Wistar; Quercetin; Tabebuia; Plant Extracts; Obesity; Adipose Tissue; Body Weight; Anti-Inflammatory Agents; Inflammation; Diet, High-Fat
PubMed: 37175211
DOI: 10.3390/molecules28093801