Clinical Review of Long-term Drug Treatment of Obesity

Background 

Obesity is currently one of the main public health problems in US and other parts of the world, particularly in developed countries. [9] The prevalence of obesity is rapidly increasing in developed countries. According to the latest report on the prevalence of obesity, it is estimated that about 2.1 billion people are obese or overweight, which accounts for about 30% of the total world population. The world has experienced a significant rise in obesity cases over the last decade, and the problem is not only limited to developed countries, but also in developing nations across the globe. Besides, obesity is affecting people of all ages and gender. [9] It is estimated that the highest number of obese people in the world live in United States of America (USA), as 13% of the global obesity cases is reported in US. Both China and India account for 15% of the total number of obese people in the world. At the same time, the number of people living with obesity in emerging and developing countries is currently high. 

CDC found out that obesity is mainly caused by the imbalance between the amount of calories consumed and those that are expended in the body. [2] The number of obese people has been rising due to an increased intake of energy-dense foods that contain a lot of fat, sugar, and salt. It is also associated with an increase in physical inactivity, which is linked to the sedentary nature of modern life, transformation in modes of transportation, and increasing urbanization. The current dietary and physical activity patterns that cause obesity are due to environmental and societal changes as well as lack of appropriate policies in key sectors such as agriculture, health, transport and urban planning. Unfortunately, obesity is associated with various health problems such as cardiovascular diseases, musculoskeletal disorders, and chronic diseases like cancer. The risk of these health problems increases with an increase body mass index (BMI). 

A number of interventions are being taken by individuals, health agencies, and governments to address obesity problem. Many lifestyle interventions are now being encouraged among populations in order to address obesity. For instance, people are encouraged to eat foods that contain less fat and sugar, increase the consumption of fruits and vegetable, and engage in regular physical activities. However, studies have proved that lifestyle interventions alone cannot make people to lose sufficient weight that can solve obesity cases. Consequently, people are now seeking alternative methods like medication, electrical devices, and surgery in order to lose sufficient weight. The percentage of adults suffering from obesity is much higher compared to that of children. For instance, in the US, it is estimated that 35% of adults are obese compared to 17% of all children and adolescents in the country. Therefore, it is important to find solutions to obesity cases among adults in various parts of the world, including USA. As a result, the primary purpose of this paper is to review drugs currently approved in the United States for obesity treatment among adults. [2] 

Literature Review 

According to the latest report that was released by the World Health Organization in 2015, as of 2014, about 1.9 billion adults were overweight, and 600 million were suffering from obesity. The statistics showed that about 13% of adult population is obese globally. [14] The same report also revealed that more adult women than men are obese, as it showed that 11% of men are suffering from obesity compared to 15% of women. [14] Adult women are also leading in terms of overweight because they constitute 40% of world’s population that is obese while men comprise of 38%. At the same time WHO found that the world prevalence of obesity has doubled between 1980 and 2014. Therefore, based on the study that was carried out by WHO, the number of adults who are suffering from obesity keeps on increasing and more women are more likely to be obese compared to men. 

Based on the study that was conducted by the Institute for Health Metrics and Evaluation (IHME), obesity among adults has been increasing over the last decade. Obesity prevalence among men has increased from 29% to 37% while that of women has increased from 30% to 38% of the last decade. [8] The same research also indicated that men in developed countries have higher rate of obesity compared to their women. However, in developing countries, women have higher rates of obesity compared to men. IHME also found that the rate of obesity among adults is rapidly increasing in developing countries. 

United States of America is still leading in terms of the rate of obesity globally. The highest proportion of people living with obesity lives in the US, and they comprise of 13% of the total world obese population. [8] China and India, which are the most populous countries in the world, together represent 15% of the world’s obese population. Countries found in Middle East, North America, and Island nations are also registering exceptionally high rate of obesity. For instance, it was found that 58% of men and 60% of women who live in Middle East are overweight and a significant number of them are suffering from obesity. In Central America, more than 57% of adult men and 65% adult women are overweight with majority are increasingly becoming obese. Hence, the majority of obese people live in developed and emerging countries like USA, China, India, and Middle East Countries. Middle East Region has showed the largest increase in the number of people suffering from obesity globally. In developing countries found in Africa, South Africa is having the largest number of people who are obese, even though other countries in the continent are experiencing rapidly experiencing rate of obesity among adults. 

The US is not likely to escape obesity problem soon, as the number of obese adults keeps on increasing. The country has been experiencing staggering rise in the prevalence of obesity since 1999. [3] The rate of obesity among adults in the US increased by about 30% between 1999 and 2000 while that of young adults increased by about 33%. [11] There is also disparity of prevalence of obesity among states and racial groups living in the US. West Virginia is leading in terms of obesity at 37.7% while Colorado has the lowest rate of obesity at 22.3%. Generally, fives states in the US have rate of obesity of more than 35% while the 46 other states have more than 25% obesity prevalence. States that have experienced rapid growth of adult obesity in the US include Washington, West Virginia, and Colorado. It is estimated that the number of adults suffering from obesity in the US will reach 30.5% in 2020. 

According to the latest statistics that was released by CDC, Hispanic adults have obesity rate of 47% compared to non-Hispanic black adults who have a rate of 46.8%. [6] The non-Hispanic white adults, on the other hand, have obesity rate of 37.9%. The least are Asian Americans adults who gave obesity rate of 12.7%. CDC also found that the rate of obesity is higher among middle-aged adults between 40-59 years living in the US compared to young adults between 20-39 years old. [2] Non-Hispanic blacks who have higher income are likely to suffer from obesity compared to those with low income. However, higher income women are less likely to suffer from obesity compared to low-income women. Based on the CDC report, there is no significant relationship between obesity and education among men. In the contrary, more educated women are less likely to obese compared to less educated women in the US. Therefore, the rate of obesity differs from one state to another and from one racial group to another. There is also gender disparity in terms of obesity, as women are more likely to suffer from obesity compared to men. Besides, education and the levels of income also influence the rate of obesity among adults. 

Espeland found that the main lifestyle interventions that are aimed at reducing obesity include dietary changes, engaging in physical activities, and behavior therapy. [5] Behavior therapy is considered to be one of the best lifestyle interventions that can be used to effectively manage obesity among adults. Behavior therapy involves the use of behavioral strategies such as setting goals with the aim of reducing calories in the body, for instance, by 500kcal per day. [13] Behavior therapy can also involve reducing the amount of snacks and high fat and sugar foods that a person consumes in a day. However, behavior therapy alone cannon lead to a significant reduction in weight, as it must be combined with other lifestyle activities such as physical exercise for at least 30 minutes in a day. Studies have found that lifestyle interventions of between 16 and 26 weeks can lead to a mean weight loss of about 7-10% of the original weight. There is a close relationship between weight loss and reduction in the risks of cardiovascular diseases that include type 2 diabetes. Patients who stop participating in lifestyle interventions such as physical exercise and behavior therapy are more likely to regain weight. According to studies that were conducted by medical centers, the combination of weight loss medication and lifestyle counseling helps in reducing more weight in comparison to when counseling is used alone. [12] 

Xu et al. argue that even though the lifestyle interventions are the common strategies that are used by many people in order to lose weight, they are regarded as short-term interventions and not long-term strategies that can be used to achieve sustainable weight loss. [15] People using lifestyle interventions are likely to lose a significant amount of weight within six months. However, the success in weight loss is always followed by a slow regain of weight. In many cases, individuals who rely on lifestyle interventions end up regaining the same weight they lost and sometimes greater weight they had before. Nevertheless, effective combination of healthy dietary patterns and regular physical activities can lead to a relatively long-term weight loss. [15] Therefore, individuals cannot only rely on the lifestyle interventions in achieving long-term weight loss. There is need to combine both lifestyle interventions and clinical medical processes in order to have a long-term solution to obesity, which has become a public health concerns in various parts of the world, including the US. 

Surgical options have been recommended for people suffering from obesity, especially in cases where lifestyle interventions have failed to yield satisfactory results. Bariatric surgery is the most common surgical option that is preferred by many people. Bariatric surgery significantly improves a number of comorbid conditions that are associated with obesity such as diabetes, hypertension, and cardiovascular diseases that are lethal. A number of studies have shown that bariatric is more effective than lifestyle interventions when it comes to sustainable weight loss. Obesity patients who have BMI of 40kg/m 2 and above are always encouraged to use surgical option like bariatric surgery. [4] In the US, many obese people prefer to use Gastric bypass, which is one of the main types of bariatric surgery. Gastric bypass enables patients to lose an average of between 60% and 70% of their excess weight within one year. Gastric bypass helps obesity patients to maintain their newly acquired weight after the surgery for more than ten years. [4] 

Based on the study that was conducted by Erlanger & Henson , duodenal switch is another surgical option that is increasingly becoming popular in the US and other developed countries across the globe. [4] It is the same as gastric bypass in terms of procedures and effects, only that it enables patients to continue losing weight even after a year, making it one of the most sustainable strategies that can be used by obese people to lose weight. However, duodenal switch option has more side effects compared to gastric bypass because it can lead to micronutrient deficiencies and increased bowel movements that can complicate health of people trying to lose weight. In addition, adjustable band is another surgical option that can be used to reduced weight loss in the case where lifestyle interventions fail to meet the required objectives or satisfaction. It can enable a person to lose about 40% of excess weight within a year after the surgery. [4] Nevertheless, it is associated with side effects like infection and obstruction. In order to the bariatric surgery to be effective in reducing weight, patients must be highly motivated while at the same time they must be ready to comply with the lifestyle interventions such as healthy diets and engaging in regular activities. 

Unlike lifestyle interventions that are recommended by many physicians, people suffering from obesity are not always advised to go for bariatric surgery because of its limitations and some of the severe side effects. Some of the common limitation associated with the bariatric surgery includes pre-operative and post-operative complications, high cost of the surgery process, and inaccessibility of surgery options because of few physicians who have specialized in the procedure. For instance, it has been proved that bariatric surgery is linked to about 7.3% pre- and post-operative complications, which may lead to fatal health consequences of patients undergoing the surgery. About 3.5% of obese patients undergoing bariatric surgery experience serious complications, weight regain, and reoperations [3]. 

Pharmacological interventions or treatments, on the other hand, provide less invasive alternatives in comparison to bariatric surgery. However, pharmacological treatment of obesity has not been common due to the due to the a few treatment options, limited efficacy, and a lot of uncertainties about their safety and long-term side effects. [7] Consequently, a number obesity drugs have been withdrawn from the market due to safety issues, which has left physicians with limited pharmacological options. At the same time, controversies involving obesity drugs has led to a lot of confusion on how best to address obesity concern that is now endangering lives of many adults as well as children in various parts of the world. However, recently, FDA has approved various obesity drugs that can be used to treat obese people. 

Currently, only a few of medications are available to be used in the management of obesity, particularly in the US. Almost all medication options that have been approved by Food and Drug Administration (FDA) in the US for obesity are meant to be used by patients who have BMI of more than 30kg/m 2 and those with risk-related risks factors like diabetes and hypertension. [10] Some of the obesity medications that have been approved include orlistat and lorcaserin. However, there is high potential that the number of obesity drugs is likely to increase in the future as many studies are now being done by various pharmaceutical companies across the globe. The three main groups of drugs that are currently being used to manage obesity include centrally acting medications that are aimed at impairing dietary intake, medications that act peripherally to impair dietary absorption, and medications that enhance energy expenditure in the body. The majority of available obesity medications are approved to be used as short-term mechanism only, as they are associated with some side effects that may negatively affect human health. 

FDA has approved two drugs that can be used for long-term treatment of obesity and they include sibutramine and orlistat. [4] Sibutramine is an appetite suppressant that assists in blocking the neuronal uptake of norepinephrine, serotonin, and dopamine in the body. FDA has labeled the drug as Schedule VI even though it has low potential for psychological addiction. The recommended dose for sibutramine is 10mg in a day. However, the quantity of dose taken in day may vary base on the condition of the patient and the side effects. Patients who have developed sibutramine intolerance are encouraged to use 5mg in a day. Some of the side effects of the drug include an increase in diastolic blood pressure, enhance heart rate, constipation, and dry mouth. It also possible that people using sibutramine can develop life-threatening drug reaction called serotonin syndrome. 

In terms of effectiveness, sibutramine can make an obese patient to lose about 4.45kg throughout the course of the therapy. Many obese people using the drugs are able to lose a minimum of 5% of their baseline body weight when they are going through therapy. [4] Previous studies revealed that substantial reduction of weight when a person is using sibutramine takes place after two to four weeks of therapy. Besides, people who are using the drug are able to maintain their original weight loss for a period of about 18 months when they continue to take the same drug. There are also other benefits associated with the use of sibutramine such as an increase in the levels of high-density lipoprotein (HDL) and a reduction in the levels of triglycerides. 

Orlistat is a nonsystematic inhibitor drugs that helps in the breakdown of fats in the GI tube. The recommended dose for the drug is 120mg three times in a day, and it should be taken one hour after consuming fat-containing food. [4] The use of the drug can be skipped if an obese person consumes foods that do not contain fats. It can help in blocking the absorption of about 30% of dietary fats. In order to enhance the effectiveness of the drug, patients are encouraged to consume foods that contain fat-soluble vitamins like such as vitamin A, D, and E. Orlistat is associated with side effects like abdominal pain, increase defecation and flatulence. The side effects linked with the drugs is known to reduce with time. Orlistat can produce a weight loss of about 2.9kg or more within a period of one year. Therefore, in terms of effectiveness, sibutramine leads to greater weight loss compared to Orlistat. Other drugs that have been approved for long-term use by FDA include Lorcaserin, Naltrexone-Bupropion, Phentermine-Topiramate, and Liraglutide. [16] Apart from Orlistat and sibutramine, FDA has also approved many other drugs that can be used to treat obesity, only that they are not recommended for long-term use. Some of the approved drugs for short-term use include phentermine. Phentermine is known as one of the most effective drugs in reducing the excess body weight for people suffering from obesity. 

Bupropion is a common drug that is used by obese people to reduce excess weight. It is an anti-depressant drug that is used to reduce appetite of obese people. Bupropion is used hand in hand with Naltrexone, which helps in blocking the effects of people using hard drugs like narcotics and alcohol. [1] Naltrexone mainly helps in reducing hunger and food cravings that can lead to excess eating on unhealthy foods that contain a lot of fats and sugar. The two drugs are used together to manage weight among obese people and those who have weight-related medical problem. However, according to Billes, Sinnayah, and Cowley , the drugs are not capable of treating any weight-related medical condition such as diabetes and hypertension. [1] People who have uncontrolled blood pressure opioid addition, eating disorder and women who are pregnant are not supposed to use the two drugs. Some of the common side effects of the drug include swollen glands, joint pains, mouth sores, and chest pains that are associated with difficulty in breathing. 

The available clinical studies have proved that the joint use of Bupropion and Naltrexone can help in reducing excess weight among patients suffering from obesity. [7] The combination of the two drugs generates greater weight loss than expected when they are used individually. The drugs lead to substantial reduction on abdominal and total body fat, leading to a reduction of excess weight. Studies have proved that Bupropion and Naltrexone significantly help in smoking cessation and major depressive disorders that are linked to obesity among obese adults. 

Phentermine and Topiramate are other drugs that are used together in order to treat obesity, and they have been approved by FDA. However, it is not yet clear how the combination of the two drugs can help obese patients lose weight. They can either act by reducing appetite, increasing the amount of energy used or by affecting some parts of the brain. However, Phentermine is an appetite suppressant while Topiramate is known to be an antiepileptic drug. Unlike other obesity drugs that have clear dose prescription, Phentermine and Topiramate do not have clear dosage, and they are taken based on the condition of the patient. The dose is also influenced by patient’s response to treatment. One of main side effect of these drugs is that they can lead to addiction, especially when they are used by patients who have substance use disorders. In order to reduce the risks of side effects on obese patients, people are always encouraged to start taking drugs in low doses. Phentermine and Topiramate are able to reduce excess weight by about 5kg or 5%, which is an indication that it is effective in weight management . [7] As a result, it is one of the obesity drugs that are highly recommended for people suffering from obesity. 

Therefore, based on the literature review, obesity is one of the public health problems that are posing a lot of challenges to many countries in the world, including USA. A significant number of adults living in US are suffering from obesity despite several attempts by governments and health agencies to reduce the problem. Lifestyle interventions such as engaging in physical activities, eating foods that contain less fat and sugar, and behavior therapy are still common strategies that are used to reduce obesity. However, the use of surgery options like bariatric have become common, even though they are not common among many people due to their limitations, costs, and accessibility challenges. To enhance the effectiveness of addressing obesity problem, FDA has approved a number of obesity drugs. The drugs have not only helped in providing short-term solutions but also long-term solutions to obesity con concerns. The drugs are more effective in offering sustainable solution to obesity epidemic compared to lifestyle interventions that are short-term. However, the approved drugs have side-effects that may further complicate health of obese adults. [7] 

Methods 

Research Questions 

What is the efficacy of drug treatment of obesity of lowering BMI and maintenance of non-obese weight? 

Are drugs used to treat obesity more effective than lifestyle interventions in reducing weight of obese people? 

What are the side effects of obesity drugs that have been approved by FDA? 

Study Design 

The study will mainly involve systematic review of literature that had been written by scholars. The researcher will mainly use journals, articles, and books that contain related information about the subject under study. Only recently published literature will be considered for review in this study. Besides, the selected literature must have findings that can be generalized to the target population. In addition, systematic literature review of the data collected from the randomized control trials that include overweight and obese adults treated with FDA-approved long-term weight-loss agents for at least 1 year compared to another active agent or placebo. [9] 

Types of Studies 

The majority of studies that will be used in this study will be retrieved from the internet. The researcher will mainly use scholarly search engines such as Google Scholar and the US National Library of Medicine (PMC) that contains relevant academic sources. At the same time, the researcher will utilize other relevant websites in order to find relevant studies that address prevalence of obesity, lifestyle interventions, and obesity drugs, especially those that have been approved by FDA. The studies will be limited to obesity in adults. A web search will be performed to research various randomized trials for currently-approved medications used to treat obesity; the length of each study that will be reviewed must be at least one year. [9] 

Types of Patients 

The types of patients under this study are obese adults. Specifically, the researcher will focus on obese adults who are above 20 years of age. The researcher will focus on obese patient living in the US. Only adults who are suffering from obesity will be considered in this research. 

Interventions 

The researchers will include studies in which the intervention includes medications currently approved in US for obesity treatment in adults. Some of the medication drugs that will be focused on include Orlistat, Sibutramine, Lorcaserin, Naltrexone-Bupropion, Phentermine-Topiramate, and Liraglutide. The researchers will focus on the effectiveness of the drugs in reducing excess body weight, including how they are administered and side effects. [1] 

Assessment of the Outcome 

The primary assessment of outcome will include: 

Reduction of BMI with the medication treatment. The researchers will assess the extent at which the approved obesity drugs can help in reducing BMI of patients suffering from obesity. It is expected that medical treatment will lead to a significant reduction of excess weight of obese adults. 

Long-term maintenance of appropriate BMI with medication. The researcher will assess whether the approved medication drugs are able to cause long-term reduction and maintenance of BIM after an obese patient has used the recommended drugs. [11] 

Secondary outcome, on the other hand, will focus on the side-effects of obesity drugs that have been approved by FDA. Like any other drug, Obesity medications are likely to have some side effects on the patients using them. It is important to assess the severity of side effects of the drugs. The drugs should not have severe side effects that can lead to more health complication that can endanger life of obesity patients. The drugs should be user-friendly and safe for human consumption. [10] 

Search Strategy 

The researchers will adopt search strategies that will ensure that they get accurate data that can be useful in addressing the main researcher questions raised in this study. The search strategies will be aimed at ensuring that only the best literature and studies are used in the research. Therefore, the researcher will research long-term studies that have investigated the role of FDA-approved drugs, either alone or in combination, for the management of obesity, by utilizing the keywords such as ‘obesity’, ‘appetite’, ‘drug’, ‘clinical trial’ or ‘meta-analysis’ in combination with the specific names of the FDA-approved drugs mentioned in the "Literature review" section for medications approved for adults, namely: Lorcaserin, Qsimia and Contrave. The search will be restricted to human studies that were published in English. [13] 

Besides, lay the strong foundation for the study, the researcher will use some of the reputable sources addressing the prevalence and situations of adult obesity not only in the US but the word as a whole. Therefore, the researcher will search for obesity information and statistics that have been published by reputable international organization like WHO and CDC, as they always carry out comprehensive and detailed research that generate reliable findings. Such sources can help in revealing how obesity affects people of various groups such as racial communities that are found in the US and gender disparity in obesity. [13] 

Quality Assessment 

The researchers will be keen to determine the risk of biases in studies that they will review. Bias is one of the unethical research practices that can hinder the objectivity and accuracy of the research findings. Therefore, in order to ensure that the studies that will be reviewed are of high quality, the researcher will assess the risks of biases in all the studies that will be reviewed. Secondly, the researcher will consider the methodologies that are used by the researcher to generate findings. Only studies that have used the standard research instruments will be considered for review. The researchers will avoid studies that have not clearly stated how the data was collected. Besides, data analysis methods will be taken into consideration in determining the quality of studies. After assessing all the chosen studies, quality of data will be assessed on the basis of a standard questionnaire and then the RCTs will be selected for the review. [9] 

In addition, the researcher will be interested in using studies that have been reviewed by other scholars, as they are more accurate and contain useful data can be used to address questions raised in this study. Therefore, quality of the studies that will be utilized in this research will be given priority to ensure that researcher come up with accurate and up to date results that can be generalized to the target population, which is obese adults. [9] 

Data Extraction 

The researchers will use effective data extraction techniques to ensure quality data review. A standard data extraction form will be used to accumulate specific data required for the review. The extraction will include information such as study-design, participant-characteristics, interventions, methodology, duration of the study, outcomes, and the setting of the trial. If the studies report more than one outcome, the longest-lasting outcome will be extracted. [9] 

Expected Outcome 

Importantly, the research is expected to generate findings that can assist physicians to decide which of the commonly used drug is the most efficient in both short-term and long-term. Currently, FDA has approved a number of obesity drugs that can be used by physician to treat patients suffering from obesity. However, it is not yet clear which of the available drugs is most efficient in both short-term and long-term. Therefore, by conducting this research, the researchers expect to come up with the best drugs that can be used to treat patients suffering from obesity. [13] 

Secondly, the research is expected to generate outcome clearly generates the severity of the side-effects of the drugs that have been approved by FDA to treat obesity. It is expected that the severity of the drugs will not have significant side-effects on people using them to reduce excess weight. Hence, the findings will provide useful information with regard to the side-effects of some of the drugs that have been approved by FDA to be used in treating obese adults. [13] 

In addition, the researcher expects to come up with findings that prove that obesity drugs are more effective compared to lifestyle interventions that are commonly used by obese people like behavior therapy, physical activities, and dietary interventions. Many physicians still recommend the use of lifestyle interventions to reduce obesity due to the uncertainty on the effectiveness of the available drugs and their possible negative side effects. However, this research is expected to reduce that uncertainty with regard to the use of the already approved obesity drugs. It will prove that approved drugs are effective and lead to long-term solution to obesity problems compared to lifestyle interventions that only offer short-term solutions to obesity epidemic affecting significant number of adults in the US and other parts of the world. [1] 

Therefore, this study expects to generate useful results that may be useful to physicians as well as other people suffering from obesity globally. However, the researcher will exercise a lot of objectivity, especially when it comes to data collection and analysis. Analysis of data will not be based on the already pre-informed assumptions or opinions of the researchers. Data collection and analysis will be based on objectivity in order to come up with accurate findings. It is not a must that the findings must be in line with the hypotheses and assumptions of the researchers. Besides, to ensure the integrity of this research, the researchers will adhere to research ethics. Especially, they will appropriate recognize authors of various studies that will be used to gather information and findings. They will strive to avoid plagiarism that can substantially interfere with the integrity of this research. 

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