Recent advances in the pathophysiology and pharmacological treatment of obesity: Article Review
Part 1: Background
Due to the high prevalence of obesity among children and adults alike across the globe, the World Health Organization has declared the condition a global health concern. The condition is now ranked among the five leading causes of death globally. One becomes obese when the energy they consume (usually through food intake) is greater than the energy expended (through metabolism and physical exercise, and diet-induced thermo genesis). However, research indicates that one cannot achieve weight loss by regulating these factors alone because several neurochemical pathways and chemical mediators also play a crucial role in satiety, food intake as well as in energy expenditure. For many years, scientists have endeavored to develop a weight loss drug that is effective in ensuring weight reduction with minimal side effects. Nonetheless, most compounds fail owing to either intolerable adverse effects or reduced efficacy. At the same time, safety concerns have been raised over the use of most weight reduction drugs, resulting in their withdrawal. However, many other drugs are still at various stages of clinical development. In will be interesting to know whether these drugs will succeed where others have fail in terms of containing the rising prevalence of obesity along with its associated morbidity.
Part 2: Article Summary
Chugh and Sharma (2012) noted with interest that the rising cases of obesity across the globe and the morbidity linked to it signifies unfulfilled medical requirements for effective and safe new drug therapies in the treating obesity. As such, they set out to assess the wide range of compounds and targets at various stages of clinical development used in the treatment of obesity. The researchers relied solely on secondary sources of literature that have already been published in various English-based publications, spanning from January 1985, all the way to December 2011. To conduct the literature searches, Chugh and Sharma (2012) made use of the Pub-MED database. A combination of relevant keywords such as obesity, weight loss, overweight, as well as treatment were used to facilitate in locating the desired sources from the database. In addition, the researchers also relied on various clinical trial website. Moreover, Chugh and Sharma (2012) also evaluated various bibliographies of specific references they had selected earlier for relevant articles. News and press releases were also used. In collecting information for their review, Chugh and Sharma (2012) confined their searches to the most current animal and human data.
The literature searches revealed various weight loss drugs that are undergoing development , and include among others, AgRP, neuropeptide Y, and MCH 1 compounds. These act centrally to reduce fat absorption from the GIT (gastrointestinal tract) or by reducing food intake. They can also minimize the formation of adipose tissue, besides helping to increase energy expenditure. Chugh and Sharma (2012) also found out in their literature searches that such new combinations of weight reduction drugs as bupropion plus naltrexone and topiramate plus phentermine have fewer adverse effects even as they offer enhanced efficacy.
Chugh and Sharma (2012) have also acknowledged that in recent years, the pharmacological treatment of obesity has been faced with a number of setbacks, key among them being the withdrawal of sibutramine and rimonabant. However, they argue that all is not lost since many other compounds are still in advanced trial stages. There is hope therefore that a new drug could be development and it would be directed at the initial pathophysiology of obesity as well as the associated morbidities either on its own on in combination with an agent already in use.
Part 3: Critical Analysis
When Chugh and Sharma (2012) sought to undertake this study, their aim was to assess the various compounds and targets in use in the pharmacological treatment of obesity at the various stages of clinical development. Based on the findings of their literature searches, there is ample evidence to suggest that the authors have succeeded in accomplishing this aim. Their literature search reveals among others, centrally acting drugs such as Obinepitide, an agent that inhibits food consumption by blocking the release of pancreatic polypeptide (PP) and PYY3-36, two of the hormones responsible for regulating appetite and food intake. Their search has also revealed TTP435 as yet another compound that is used in the pharmacological treatment of obesity. It acts to reduce insulin levels, food intake and body weight by inhibiting AgRP (Agouti-related protein inhibitor). The TTP435 compound, according to Chugh and Sharma (2012) is still in phase II of clinical development where it is being assessed for safety and efficacy in pharmacological treatment of obesity. Moreover, the literature search has revealed taranabant, a cannabinoid receptor antagonist that is still undergoing clinical trials. However, Chugh and Sharma (2012) report that a long-term study that has been carried out to assess the safety and efficacy of this compound when administered to obese patients revealed exceedingly higher weight loss and reduced probability to develop MetS.
The findings of a review article by Remesh (2013) concur with the findings of Chugh and Sharma (2012) on the various compounds and agents in use in the pharmacological treatment of obesity. Specifically, Remesh (2013) has identified rimonabant as an example of a peripherally and centrally acting weight loss drug whose mode of action entails regulating metabolic action and inhibiting food intake. However, Remesh (2013) notes that although this drug had initially been approved by the FDA (Food and Drug Administration), it has since been disapproved on account of psychiatric and neurological problems linked to it. The fact that Chugh and Sharma (2012) have failed to capture this crucial information provided by Remesh (2013) is in itself a source of weakness for their study. However, it could be due to the fact that Remesh’s study was published after that by Chugh and Sharma and owing to its current nature, it is bound to be more up-to-date.
Another scholarly article by Adan (2013) has also echoed the sentiments by Remesh (2013) regarding the removal of such weight reducing drugs as rimonabant and sibutramine from the market. Unlike Chugh and Sharma (2012) and Remesh (2013), Adan has also noted that other new weight reducing drugs have since been introduced into the market. These drugs, lorcaserin and Qsymia, are projected to usher in a novel approach in as far as the pharmacological treatment of obesity is concerned.
The layout of the article by While Chugh and Sharma (2012) is well done. To start with, the introduction is detailed, beginning with a vivid definition of obesity, its risk factors, and prevalence. The thesis statement of the research is also quite elaborate. The method section is not very detailed but it detailed enough. Over and above the description of literature searches, the pathophysiology of obesity has also been discussed, along with the rationale for the management of obesity. However, it is important to note that the authors have not provided a history of weight loss drugs in the pharmacological treatment of obesity. This would have been a good thing to do in order to in order to give a timeline of the use of these drugs, the various breakthroughs that have been made over the years, and the frequency of introducing new anti-obesity drugs into the market. On this aspect, the source by Adan (2013) has provided a detailed timeline on the history of the use of antiobesity drugs, starting with the use of thyroid hormone in the 19th century to the use of Qsymia and lorcaserin, which are the current drugs in the market.
It is also important to note that the authors of the article under review have deftly made use of tables and figures throughout the paper, with the aim of complementing text. For example, in one of the tables, they have depicted the different weight loss drugs and their action/targets for obesity. There is also a figure that demonstrates how food intake is regulated by various hormones such as leptin, as well as the various target sites for different weight loss drugs. Such depictions give the reader a better comprehension of the text more than they would have in their absence.
Chugh and Sharma (2012) have also tackled the issue of areas that need further research in regards to their topic of evaluation. In this case, the authors have talked on the need to conduct further research on the long-term implications of weight loss drugs on morbidity, mortality, and cardiovascular risks. This is aimed at enabling researchers to determine the risk-benefit ratio of such drugs, as well as to enhance clinically desirable outcomes of such drugs.
From the article under review, we can see that most of the references cited by Chugh and Sharma (2012) were published in the last 2 years and are hence recent. More importantly, they are directly related to the topic of study by the authors. In this respect, they are used to support the study by Chugh and Sharma.
Part 4: Conclusion
The article by Chugh and Sharma is an interesting read in field of pathophysiology. Besides exploring the recent advances in the pathophysiology of anti-obesity drugs, the authors have also endeavored to examine into details what is new in the pharmacological treatment of obesity. The study’s aim is described very well, and the authors have ensured that it has been achieved through their detailed and elaborate literature searches. Moreover, the authors of this article have heavily references the works of other scholars in the field of pathophysiology, especially with regard to obesity treatment drugs. Most of these sources were published in the last 2 years and is hence current. Although Chugh and Sharma have failed to capture in their article the latest anti-obesity drugs to be discontinued from the market for safety reasons, vital information that has been highlighted by other authors like Adan and Remesh. It could be argued that Chugh and Sharma’s paper was published before the other two and hence the reasons why it has failed to capture this information. Nevertheless, Chugh and Sharma have prevailed on researchers in the field of pathophysiology, especially those concerned with the development of new anti-obesity drugs, to consider assessing the long-term implications of these drugs on the mortality and cardiovascular risks.
Adan, R.A. (2013). Mechanisms underlying current and future anti-obesity drugs. Trends N rosci, 36(2):133-40.
Chugh, P.K., & Sharma, S. (2012). Recent advances in the pathophysiology and pharmacologicaltreatment of obesity. J Clin Pharm Ther, 37(5):525-35. Remesh, A. (2013). Obesity: Pathophysiology And Management- A Pharmacological Perspective. Asian Journal of Pharm ceutical and Clinical Research, 6(1), 11-13.