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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 -
Current Obesity Reports Mar 2024This review provides an overview of the history, mechanism of action, and expected treatment effects of the anti-obesity medication (AOM), phentermine. It also includes... (Review)
Review
PURPOSE OF REVIEW
This review provides an overview of the history, mechanism of action, and expected treatment effects of the anti-obesity medication (AOM), phentermine. It also includes a summary of recent research and practical guidance for prescribing clinicians.
RECENT FINDINGS
Recent research on phentermine is sparse and consists primarily of observational studies with methodologic limitations. These studies suggest that phentermine use is associated with clinically significant weight loss in adults and that the medication is generally well tolerated. Large-scale observational studies evaluating phentermine's safety have not identified an increased risk of cardiovascular events or elevations in blood pressure. There is no data to support the notion that phentermine is addictive. Although it remains the most commonly prescribed AOM in the USA, phentermine has little rigorous research to support its efficacy and safety in long-term treatment, which creates a dilemma with guideline-recommended chronic use of AOMs. While we await forthcoming conclusive data on this front, clinicians may consider using phentermine long-term in selected patients, if such prescribing is consistent with local regulatory statutes.
Topics: Adult; Humans; Anti-Obesity Agents; Obesity; Phentermine
PubMed: 38172485
DOI: 10.1007/s13679-023-00546-9 -
Obesity (Silver Spring, Md.) Feb 2012A 56-week randomized controlled trial was conducted to evaluate safety and efficacy of a controlled-release combination of phentermine and topiramate (PHEN/TPM CR) for... (Randomized Controlled Trial)
Randomized Controlled Trial
A 56-week randomized controlled trial was conducted to evaluate safety and efficacy of a controlled-release combination of phentermine and topiramate (PHEN/TPM CR) for weight loss (WL) and metabolic improvements. Men and women with class II and III obesity (BMI ≥ 35 kg/m(2)) were randomized to placebo, PHEN/TPM CR 3.75/23 mg, or PHEN/TPM CR 15/92 mg, added to a reduced-energy diet. Primary end points were percent WL and proportions of patients achieving 5% WL. Secondary end points included waist circumference (WC), systolic and diastolic blood pressure (BP), fasting glucose, and lipid measures. In the primary analysis (randomized patients with at least one postbaseline weight measurement who took at least one dose of assigned drug or placebo), patients in the placebo, 3.75/23, and 15/92 groups lost 1.6%, 5.1%, and 10.9% of baseline body weight (BW), respectively, at 56 weeks (P < 0.0001). In categorical analysis, 17.3% of placebo patients, 44.9% of 3.75/23 patients, and 66.7% of 15/92 patients, lost at least 5% of baseline BW at 56 weeks (P < 0.0001). The 15/92 group had significantly greater changes relative to placebo for WC, systolic and diastolic BP, fasting glucose, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). The most common adverse events were paresthesia, dry mouth, constipation, dysgeusia, and insomnia. Dropout rate from the study was 47.1% for placebo patients, 39.0% for 3.75/23 patients, and 33.6% of 15/92 patients. PHEN/TPM CR demonstrated dose-dependent effects on weight and metabolic variables in the direction expected to be beneficial with no evidence of serious adverse events induced by treatment.
Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Body Weight; Delayed-Action Preparations; Drug Combinations; Female; Fructose; Humans; Lipoproteins, LDL; Male; Middle Aged; Obesity, Morbid; Phentermine; Topiramate; Weight Loss; Young Adult
PubMed: 22051941
DOI: 10.1038/oby.2011.330 -
The Annals of Pharmacotherapy Mar 2013To review the pharmacology, efficacy, and safety of phentermine/topiramate (PHEN/TPM) in the management of obese patients. (Review)
Review
OBJECTIVE
To review the pharmacology, efficacy, and safety of phentermine/topiramate (PHEN/TPM) in the management of obese patients.
DATA SOURCES
MEDLINE (1966-July 2012) was searched using the terms weight loss, obesity, phentermine and topiramate, phentermine, topiramate, Qnexa, Qsymia, and VI-0521. Additionally, the new drug application and prescribing information for PHEN/TPM were retrieved.
STUDY SELECTION/DATA EXTRACTION
All studies considering the pharmacology, efficacy, and safety of PHEN/TPM were reviewed with a focus on efficacy and safety data from Phase 3 trials.
DATA SYNTHESIS
In 3 Phase 3 trials (EQUIP, CONQUER, and SEQUEL), treatment with PHEN/TPM consistently demonstrated statistically significant weight loss compared with placebo. After 56 weeks of treatment, percent weight loss achieved with PHEN/TPM was 10.6%, 8.4%, and 5.1% with 15/92 mg, 7.5/46 mg, and 3.75/23 mg, respectively (p < 0.0001). The 52-week extension study (SEQUEL) showed maintained weight loss over 2 years with 9.3% and 10.5% weight loss from baseline for 7.5/46 mg and 15/92 mg PHEN/TPM (p < 0.0001). A significantly higher proportion of patients achieved greater than 5%, 10%, or 15% weight loss with PHEN/TPM compared with placebo. Significant reductions in waist circumference, fasting triglycerides, and fasting glucoses were also attributable to PHEN/TPM. The drug was generally well tolerated in clinical trials. Adverse reactions occurring in 5% or more of study subjects included paresthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.
CONCLUSIONS
PHEN/TPM is a new, once-daily, controlled-release, combination weight-loss product approved as an adjunct to diet and exercise for chronic weight management of obese or overweight patients with weight-related comorbidities. PHEN/TPM is modestly effective and a viable option for patients interested in losing weight, although long-term safety data are lacking.
Topics: Anti-Obesity Agents; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Topiramate
PubMed: 23482732
DOI: 10.1345/aph.1R501 -
The American Journal of Clinical... Feb 2012Obesity is a serious chronic disease. Controlled-release phentermine/topiramate (PHEN/TPM CR), as an adjunct to lifestyle modification, has previously shown significant... (Randomized Controlled Trial)
Randomized Controlled Trial
Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study.
BACKGROUND
Obesity is a serious chronic disease. Controlled-release phentermine/topiramate (PHEN/TPM CR), as an adjunct to lifestyle modification, has previously shown significant weight loss compared with placebo in a 56-wk study in overweight and obese subjects with ≥2 weight-related comorbidities.
OBJECTIVE
This study evaluated the long-term efficacy and safety of PHEN/TPM CR in overweight and obese subjects with cardiometabolic disease.
DESIGN
This was a placebo-controlled, double-blind, 52-wk extension study; volunteers at selected sites continued with original randomly assigned treatment [placebo, 7.5 mg phentermine/46 mg controlled-release topiramate (7.5/46), or 15 mg phentermine/92 mg controlled-release topiramate (15/92)] to complete a total of 108 wk. All subjects participated in a lifestyle-modification program.
RESULTS
Of 866 eligible subjects, 676 (78%) elected to continue in the extension. Overall, 84.0% of subjects completed the study, with similar completion rates between treatment groups. At week 108, PHEN/TPM CR was associated with significant, sustained weight loss (intent-to-treat with last observation carried forward; P < 0.0001 compared with placebo); least-squares mean percentage changes from baseline in body weight were -1.8%, -9.3%, and -10.5% for placebo, 7.5/46, and 15/92, respectively. Significantly more PHEN/TPM CR-treated subjects at each dose achieved ≥5%, ≥10%, ≥15%, and ≥20% weight loss compared with placebo (P < 0.001). PHEN/TPM CR improved cardiovascular and metabolic variables and decreased rates of incident diabetes in comparison with placebo. PHEN/TPM CR was well tolerated over 108 wk, with reduced rates of adverse events occurring between weeks 56 and 108 compared with rates between weeks 0 and 56.
CONCLUSION
PHEN/TPM CR in conjunction with lifestyle modification may provide a well-tolerated and effective option for the sustained treatment of obesity complicated by cardiometabolic disease. This trial was registered at clinicaltrials.gov as NCT00796367.
Topics: Adult; Anti-Obesity Agents; Cardiovascular Diseases; Delayed-Action Preparations; Diabetes Mellitus; Double-Blind Method; Drug Combinations; Female; Fructose; Humans; Incidence; Intention to Treat Analysis; Least-Squares Analysis; Male; Metabolic Diseases; Middle Aged; Obesity; Overweight; Patient Dropouts; Phentermine; Time; Topiramate; Weight Loss
PubMed: 22158731
DOI: 10.3945/ajcn.111.024927 -
Handbook of Experimental Pharmacology 2022Older medications approved for chronic weight management (orlistat, naltrexone/bupropion, liraglutide 3 mg and, in the USA, phentermine/topiramate) have not been widely...
Older medications approved for chronic weight management (orlistat, naltrexone/bupropion, liraglutide 3 mg and, in the USA, phentermine/topiramate) have not been widely adopted by health care providers. Those medications produce only modest additional weight loss when used to augment lifestyle intervention. However, semaglutide 2.4 mg weekly has recently emerged and produces much more weight loss - on average 15% weight loss at 1 year. Semaglutide's enhanced efficacy and that its class (GLP-1 receptor analogs) is well-known may result in more clinicians adopting pharmacotherapy. Furthermore, the first dedicated cardiovascular outcome trial powered for superiority testing an anti-obesity medication (SELECT) is underway with semaglutide 2.4 mg. A positive outcome will further promote the concept that weight management should be a primary target for cardiometabolic disease control. In phase 3, tirzepatide and cagrilintide/semaglutide combination are showing promise for even greater weight loss efficacy. Another recently approved medication takes a personalized medicine approach; setmelanotide is approved as a therapy for those with some of the ultra-rare genetic diseases characterized by severe, early onset obesity. This chapter reviews the currently available and anticipated medications for chronic weight management as well as those approved for the genetic and syndromic obesities.
Topics: Anti-Obesity Agents; Humans; Islet Amyloid Polypeptide; Obesity; Phentermine; Weight Loss
PubMed: 34783910
DOI: 10.1007/164_2021_560 -
Drug Design, Development and Therapy 2013Obesity is now a major public health concern worldwide with increasing prevalence and a growing list of comorbidities and complications. The morbidity, mortality and... (Review)
Review
Obesity is now a major public health concern worldwide with increasing prevalence and a growing list of comorbidities and complications. The morbidity, mortality and reduced productivity associated with obesity and its complications result in a major burden to health care costs. Obesity is a complex chronic medical syndrome often with multiple different etiologic factors in individual patients. The long term successful management of obesity remains particularly challenging and invariably requires a multifaceted approach including lifestyle and behavioral modification, increased physical activity, and adjunctive pharmacotherapy. Bariatric surgery remains a last resort though at present it has the best results for achieving sustained robust weight loss. Obesity pharmacotherapy has been very limited in its role for long term obesity management because of the past history of several failed agents as well as the fact that presently available agents are few, and generally utilized as monotherapy. The recent FDA approval of the fixed drug combination of phentermine and extended release topiramate (topiramate-ER) (trade name Qsymia™) marks the first FDA approved combination pharmacotherapeutic agent for obesity since the Phen-Fen combination of the 1990s. This review details the history and clinical trial basis for the use of both phentermine and topiramate in obesity therapeutics as well as the results of clinical trials of their combination for obesity treatment in humans. The initial clinical approval trials offer evidence that this fixed drug combination offers synergistic potential for effective, robust and sustained weight loss with mean weight loss of at least 10% of baseline achieved and sustained for up to 2 years in over 50% of subjects treated. It is anticipated that this agent will be the first in a new trend of multi-agent combination therapy for the chronic adjunctive management of obesity.
Topics: Anti-Obesity Agents; Clinical Trials as Topic; Drug Therapy, Combination; Fructose; Humans; Obesity; Phentermine; Topiramate
PubMed: 23630412
DOI: 10.2147/DDDT.S31443 -
The Medical Letter on Drugs and... Dec 2016
Review
Topics: Anti-Obesity Agents; Drug Approval; Humans; Obesity; Phentermine; Weight Loss
PubMed: 27906152
DOI: No ID Found -
Drug and Alcohol Dependence Jan 2021Cocaine use disorder is an unrelenting public health concern. Despite nearly four decades of research, an FDA approved medication is not yet available.
RATIONALE
Cocaine use disorder is an unrelenting public health concern. Despite nearly four decades of research, an FDA approved medication is not yet available.
OBJECTIVES
The objective of this human laboratory study was to demonstrate the initial efficacy, safety and tolerability of topiramate-phentermine combinations for cocaine use disorder.
METHODS
Thirty-one (31) participants with cocaine use disorder completed this mixed-model inpatient laboratory study. Participants were maintained on topiramate (0 [N = 11], 50 [N = 9] or 100 [N = 11] mg/day). Each topiramate group was concurrently maintained on phentermine (0, 15, 30 mg). Drug self-administration, subjective responses and cardiovascular effects following acute doses of intranasal cocaine (0, 40, 80 mg) were determined during separate experimental sessions after at least seven (7) days of maintenance on each condition.
RESULTS
The three groups of participants were well matched demographically and generally did not differ significantly in their responses to a range of doses of intranasal cocaine (0, 10, 20, 40, 80 mg) during a medical safety session. Maintenance on topiramate and phentermine alone significantly decreased cocaine self-administration although these effects were modest in magnitude. Combining topiramate and phentermine robustly decreased cocaine self-administration. Topiramate and phentermine were well tolerated alone and combined, as well as in conjunction with cocaine.
CONCLUSIONS
The results of the present study support advancing topiramate-phentermine combinations as a putative pharmacotherapeutic for cocaine use disorder.
Topics: Adult; Cocaine; Cocaine-Related Disorders; Drug Combinations; Female; Fructose; Humans; Male; Middle Aged; Phentermine; Self Administration; Topiramate; Young Adult
PubMed: 33290875
DOI: 10.1016/j.drugalcdep.2020.108413 -
Diabetes & Metabolism Journal Dec 2020Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and... (Review)
Review
Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and heterogeneous disease influenced by genetic, developmental, biological, and environmental factors, it is necessary to approach obesity with an integrated and comprehensive treatment strategy. As it is difficult to achieve and sustain successful long-term weight loss in most patients with obesity through lifestyle modifications (e.g., diet, exercise, and behavioral therapy), pharmacological approaches to the treatment of obesity should be considered as an adjunct therapy. Currently, four drugs (orlistat, naltrexone extended-release [ER]/bupropion ER, phentermine/topiramate controlled-release, and liraglutide) can be used long-term (>12 weeks) to promote weight loss by suppressing appetite or decreasing fat absorption. Pharmacotherapy for obesity should be conducted according to a proper assessment of the clinical evidence and customized to individual patients considering the characteristics of each drug and comorbidities associated with obesity. In this review, we discuss the mechanisms of action, efficacy, and safety of these available long-term anti-obesity drugs and introduce other potential agents under investigation. Furthermore, we discuss the need for research on personalized obesity medicine.
Topics: Anti-Obesity Agents; Benzazepines; Humans; Orlistat; Phentermine; Weight Loss
PubMed: 33389955
DOI: 10.4093/dmj.2020.0258