# From Obesity to Efficacy: A Comprehensive Analysis of Emerging Weight Loss Drugs

Hani Karrar, Mahmoud Ismail Karrar, Sarah Nouh, Salman Wasan, Hani

Raka Karrar, Sarah Abdulhadi Alanazi, Salman Alanazi, Abdelbagi

Abdelmageed, Mohammed Abdelmageed, Amuna Hamad, et al.

► To cite this version:

Hani Karrar, Mahmoud Ismail Karrar, Sarah Nouh, Salman Wasan, Hani Raka Karrar, et al. From Obesity to Efficacy: A Comprehensive Analysis of Emerging Weight Loss Drugs. Journal of Pharmaceutical Research International, 2025, 10.9734/jpri/2025/v37i127800. hal-05446802

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# From Obesity to Efficacy:
A Comprehensive Analysis of
Emerging Weight Loss Drugs

Hani Raka Karrar a*, Mahmoud Ismail Nouh b++, Sarah abdulhadi Alanazi c, Wasan Salman Alanazi d, ABDELBAGI ABDELMAGEED MOHAMMED ABDELMAGEED e, Amuna Hamad Awaji f, Yassir abubakar fikak g and Barakat Ali Alshmrany h

a Pharmaceutical Care Services, Dr. Samir Abbas Hospital, Jeddah, Saudi Arabia.

b Chairman of Research and Continues Education Committees in Pharmacy Department at King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia.

c Pharmacy Department, Aldawa Company, Arar, Saudi Arabia.

d Pharmaceutical Care Services, Northern Border Region, Arar, Kingdom of Saudi Arabia.

e Surgical Department, Abha Private Hospital, Abha, Saudi Arabia.

f Nursing Department, King Fahd Security College Medical Center, Riyadh, Saudi Arabia.

g Department of Pharmacology, Saharanpur, Uttar Pradesh, India.

h Pharmaceutical Care Services, Northern Area Armed Forces Hospital, Northern Area, Saudi Arabia.

## Authors' contributions

This work was carried out in collaboration among all authors. All authors read and approved the final manuscript.

## Article Information

DOI: https://doi.org/10.9734/jpri/2025/v37i127800

**Open Peer Review History:**
This journal follows the Advanced Open Peer Review policy. Identity of the Reviewers, Editor(s) and additional Reviewers, peer review comments, different versions of the manuscript, comments of the editors, etc are available here: https://pr.sdiarticle5.com/review-history/150721

## Review Article

Received: 16/10/2025

Published: 31/12/2025

<footnote>** 0000-0002-6264-6996;</footnote>

<footnote>* Corresponding author: E-mail: Hanywell2022@gmail.com;</footnote>
ABSTRACT

Obesity has emerged as a critical global health crisis in the 21st century, as defined by the World Health Organization (WHO) with a body mass index (BMI) of 30 or higher. This condition greatly raises the risk of getting a number of long-term diseases, such as type 2 diabetes, heart disease, high blood pressure, and many types of cancer. In the last few decades, obesity has become much more common, almost tripling since 1975. Poor diet, lack of exercise, mental health problems, and socio-economic problems are all factors that contribute to the epidemic's complexity. To deal with obesity, we need a comprehensive approach that includes changes to our lifestyle, psychological support, and medicine. Making changes to your lifestyle, like eating better and getting more exercise, is a key part of managing your weight, but they often don't work for many people, especially those who are very overweight. As a result, pharmacotherapy has become an essential tool, particularly for individuals who have not achieved significant weight loss through non-pharmacological means. Traditional weight loss medications, such as phentermine and orlistat, have paved the way for current treatments but are often limited by adverse effects and varying efficacy across patients. This has spurred an increase in research and development focused on novel agents. Among these, GLP-1 receptor agonists—like semaglutide—have shown significant promise, alongside newer combination therapies that target various biological mechanisms involved in weight regulation. These contemporary pharmacological options not only facilitate weight loss but also aim to address underlying metabolic and psychological factors that contribute to obesity. Moreover, the ever-changing treatment environment indicates an alignment toward comprehensive management strategies that are more adaptable towards the complexities associated with obesity. In other words, the comprehensive treatment approach indicates promise in improving treatment outcomes, minimizing the risks of obesity as an underlying cause for various health ailments, and finally mitigating the adverse effects that come along with this harmful health issue. In the ongoing process of unraveling further studies, the effectiveness of customized treatment plans, which include pharmacological management, lifestyle, and psychology, becomes paramount in the ongoing battle against the prevalence of obesity.

Keywords: Obesity; Body Mass Index (BMI); chronic illnesses; public health; weight management; pharmacotherapy.

1. INTRODUCTION

Obesity is a significant global health issue in the 21st century. The WHO defines obesity as a body mass index of 30 or greater (Hurt et al., 2010). Obesity is a multifactorial disease that significantly increases the risk for a number of chronic conditions, including type 2 diabetes, CVD, hypertension, and various malignancies. Public health campaigns, clinical investigation, and pharmaceutical development have increasingly addressed this disorder, as the prevalence of obesity has grown dramatically worldwide in recent decades (Wang et al., 2025). Recent WHO figures indicate that global obesity has nearly tripled since 1975, with over 1.9 billion adults categorized as overweight, of which more than 650 million are deemed obese. Moreover, childhood obesity is increasing, impacting millions of youngsters globally (Alsulami et al., 2023). There are many reasons why this epidemic is getting worse, including changes in eating habits, lack of exercise, mental health issues, and economic problems. Obesity has

become a public health problem that needs new solutions, like changes to people's daily lives, mental health support, and medications (Mitchell et al., 2011). Even though lifestyle changes such as diet and physical activity are fundamental approaches in weight management, they often fail to work effectively in most cases, particularly in patients who suffer from severe cases of obesity. In such patients, pharmacological approaches become an important tool in losing weight effectively and managing health risks associated with such conditions. In modern days, there has been a rise in investments in innovative weight loss drugs (Aragón-Martín et al., 2022).

2. THE BURDEN OF OBESITY

The main purpose of dealing with obesity is to make people healthier. If you lose more than 10% of your body weight, it can assist with a lot of the problems that come with being overweight, like stopping and treating type 2 diabetes, high blood pressure, fatty liver disease, and
obstructive sleep apnea. It can also make your life better. The hardest part of dealing with obesity is keeping the weight off. Obesity, similar to numerous chronic conditions, necessitates a comprehensive, enduring strategy that takes into account individual treatment objectives and the advantages and disadvantages of various therapies (Ryan and Yockey, 2017). Anti-obesity drugs and bariatric surgery make it simpler to keep the weight off and gain the health benefits that come with it, in addition to changes in lifestyle. Most of the anti-obesity medicines that are available focus on the brain's appetite control systems to make people less hungry and less likely to enjoy food (Tak and Lee, 2021). Obesity is a difficult problem for both people and society as a whole. People who are obese often face social stigma, mental health issues, and a lower quality of life on top of the physical health problems that come with it. There are big economic effects; the cost of treating diseases caused by obesity is expected to be billions of dollars a year. In the United States, healthcare costs associated with obesity were anticipated to surpass $170 billion each year. The global economic burden significantly strains healthcare systems that are already challenged by resource allocation issues (Westbury et al., 2023, Albashir, 2020).

### 3. MECHANISMS OF OBESITY

There are many biological, environmental, and behavioral factors that make people obese. Genetics, metabolism, and neuroendocrine pathways contribute to the etiology of this disorder. The following ideas explain how these elements work together to cause obesity:

1. Genetic Factors: Genetic predisposition has a major impact on weight regulation, including metabolism, fat distribution, and hunger. Twin and familial studies demonstrate that genetic factors account for approximately 40-70% of the risk of obesity. Advancements in genetic research continually reveal genes and regions associated with obesity (Młynarska et al., 2025).

2. Metabolic Factors: Metabolic syndrome, with its insulin resistance, lipid abnormalities, or hypertension, presents a pathway commonly used by obesity in developing some adverse outcomes. A relationship between obesity and metabolism could form a vicious cycle whereby metabolism could worsen obesity (Jin et al., 2023).

3. Environmental Influences: The environments that people live in are highly influential of the food that they consume and the exercise that they do. Considerations such as the availability of healthy food and the availability of healthy spaces to exercise can either facilitate or impede the control of weight (Ball et al., 2006).

4. Psychological Factors: Stress, depression, and anxiety are just a few of the emotional components that can cause people to eat more and make unwise choices in terms of health. Behavioral therapy that revolves around mental health can be a very crucial element of weight management plans (Molina et al., 2021).

5. Endocrinological Factors: Hormonal imbalances, particularly involving ghrelin and leptin, may influence hunger and satiety signals. Understanding the neuroendocrine mechanisms involved in weight regulation has led to the development of new types of weight loss drugs (Vijayashankar et al., 2024).

### 4. THE ROLE OF PHARMACOTHERAPY

Weight loss drugs are an important part of a full plan for treating obesity, especially for people who haven't had much success with just making changes to their lifestyle. People who are very overweight can lose a lot of weight through surgery, such as bariatric surgery. However, medicines are a less invasive option that can also work well. In the past, a lot of people were against taking drugs to help them lose weight because they were worried about safety, especially the risk of heart problems and addiction. New research into medications has changed this field completely, leading to new drugs that help people lose weight while being safer (Louis and Velazquez, 2025).

### 5. CURRENT LANDSCAPE OF WEIGHT LOSS DRUGS

Over time, the approval process for weight loss drugs has changed. It has gone from simple appetite suppressants to more complicated drugs that target many of the body's processes that cause obesity. Phentermine, and orlistat are older drugs that are commonly used to help people lose weight. They work in different ways, but they often have adverse effects or don't work as well as they should (Abdi Beshir et al., 2023, Lewis et al., 2024).
* New Developments: Recent advancements in pharmacology, such as glucagon-like peptide-1 (GLP-1) receptor agonists, selective serotonin reuptake inhibitors, and combination therapy, represent significant advances. Clinical trials have indicated that drugs like semaglutide and orlistat can help people lose a lot of weight.

* The FDA has started to rethink the rules for approving drugs by focusing on the overall benefits of weight loss on metabolic health rather than just the number on the scale. This new way of thinking has led to the development and use of new agents, which is a very promising area for people who are having trouble with their weight (Olukorode et al., 2024, Jensterle et al., 2024).

# 6. OVERVIEW OF WEIGHT LOSS DRUGS

Historically, weight loss medications have faced suspicion due to their harmful effects and limited efficacy. Newly emerging pharmacotherapies have resulted in the identification of a number of promising drugs being developed. These drugs are mainly focused on mechanisms such as appetite inhibition, raising the metabolic rate, and inhibiting the absorption of fats (Bray and Purnell, 2022).

# 7. TRADITIONAL WEIGHT LOSS MEDICATIONS

Before looking at the new options, it's important to remember how important traditional weight loss medications are, since they have paved the way for new treatments.

* Phentermine: This appetite suppressant based on stimulants has been an important part of weight management for many years. Phentermine changes the way the central nervous system works to reduce hunger signals, making it easier to stick to calorie-restricted diets. While effective for short-term weight control, dependence and cardiovascular side effects hinder its long-term use (Kokkorakis et al., 2025, Henness and Perry, 2006, Bays et al., 2022).

* Orlistat: As a lipase inhibitor, orlistat stops the intestines from absorbing fat from food. This approach helps some people lose weight because it makes them eat less calories. However, gastrointestinal side effects including oily stools and gas may

be big reasons why people don't want to keep taking the drug (Kokkorakis et al., 2025, Henness and Perry, 2006, Bays et al., 2022).

* Lorcaserin is a selective serotonin receptor agonist that increases feelings of fullness by changing how serotonin works in the brain. Although advantageous for some individuals, its clearance was rescinded due to concerns over an increased cancer risk, underscoring the imperative for meticulous monitoring of the long-term effects of weight reduction medications (Kokkorakis et al., 2025, Henness and Perry, 2006, Bays et al., 2022).

While these older drugs have been effective in yielding desirable results for some patients, they also bring into sharp focus the intrinsic blemishes and risks of pharmacological weight loss methods. The current situation has resulted in huge interest and investment in new drugs that rely not only on efficacy but also on safety and tolerability. This marks the beginning of a new era in obesity management (Burke et al., 2017, Pirtle et al., 2019).

# 8. EMERGING WEIGHT LOSS DRUGS

Recent years have seen the introduction of several new weight loss drugs that offer different mechanisms of action:

**GLP-1 Receptor Agonists:** GLP-1 (Glucagon-like Peptide-1) receptor agonists are a type of medicine that works like the hormone GLP-1, which is made by the intestines after eating. Their mechanism of action includes several important physiological processes that work towards weight loss and the optimization of metabolic syndrome: GLP-1 Receptor Agonists: They talk to the brain so that they can reduce hunger. They act on the GLP1 receptor located in the hypothalamus part of the brain. They reduce hunger so that a person can eat less because of the reduced hunger. They induce the increase of insulin secretion from the pancreas. It secretes insulin based on the glucose level in the blood. It increases insulin secretion because high blood sugars result in the high secretion of insulin. It reduces the secretion of the hormone glucagon because it increases blood sugar because it degrades the glycogen in the liver. These drugs help keep blood sugar levels more steady by lowering the amount of glucagon that is released (Collins and Costello, 2024). Delayed Gastric Emptying: GLP-1 receptor agonists prolong postprandial satiety by slowing down the process of gastric emptying. This delayed
stomach emptying helps to lower the amount of food eaten overall. Weight Loss: The combined effects of lowering hunger, increasing insulin secretion, and keeping the stomach empty for longer periods of time lead to a lot of weight loss. Clinical studies have shown that people taking GLP-1 receptor agonists can lose a lot of weight, making them effective tools for controlling obesity. Often Used Agonists of the GLP-1 Receptor (Moiz et al., 2025). There are now many GLP-1 receptor agonists that are approved for weight loss and controlling diabetes. Some well-known examples are Semaglutide (Wegovy, Ozempic): Approved for treating obesity and controlling type 2 diabetes. Liraglutide (Saxenda, Victoza): Used for controlling diabetes and managing weight. Dulaglutide (Trulicity) is mostly used to treat type 2 diabetes, but losing weight is a good side effect (Ghusn et al., 2022, Lundgren et al., 2021, Li et al., 2024).

Tirzepatide (Zepbound) The FDA approved Zepbound, a dual GIP/GLP-1 agonist, on November 8, 2023. It is given as an injection once a week. Clinical studies have shown that it works quite well, with people losing an average of around 21% of their body weight, or about 48 pounds (21.8 kg), with a weekly dose of 15 mg. This big weight loss shows that Zepbound can be a good option for patients who are overweight or have health problems related to their weight (Samms and Sloop, 2025). However, a lot of studies have also been conducted regarding its safety concerning GLP-1 agonists, and it is largely positive, but there are a few large concerns regarding these drugs. The most prevalent negative gastrointestinal reaction includes nausea, vomiting, diarrhea, and abdominal pain. This commonly occurs when a

patient initially begins taking the drugs, though it might fade away once the body gets accustomed to it. Healthcare professionals usually advise increasing doses to decrease unpleasant feelings (Karrar et al., 2023). Risk of Pancreatitis: There have been reported cases of those with a GLP-1 receptor agonist developing acute pancreatitis. Healthcare professionals recommend being vigilant about the warning signs of pancreatitis even if its cause has not yet been identified and may include abdominal pain. Glycemic Control: These medications are effective in regulating blood sugar levels; however, they may induce symptoms such as hypoglycemia. However, they may induce symptoms such as hypoglycemia. However, when they are taken to aid in weight loss, they do not induce severe hypoglycemia since their effect on insulin cell secretion is concentration-dependent (Fisman and Tenenbaum, 2021). Thyroid Tumor Risk: Experiments conducted in rats provide evidence in relation to medullary carcinoma that is associated with the risk of GLP-1 receptor agonists. The U.S. Food and Drug Administration (FDA) has warned of possible thyroid cancers, even though there is no proof in individuals. This has led to precautions for patients who have a personal or family history of thyroid cancer (Kamrul-Hasan et al., 2025). Effects on the heart: Several GLP-1 receptor agonists have been shown to provide benefits for the heart, notably in those with type 2 diabetes. Research indicates that these drugs lower the risk of large cardiovascular events, including myocardial infarction and cerebrovascular accident. It is an added advantage that this is not a safety concern, given that obese people are usually prone to cardiovascular diseases (Zile et al., 2025).

<table><caption>Table 1. Comparative summary</caption><thead><tr><td>Therapy</td><td>Average Weight Loss</td><td>Mechanism of Action</td><td>Common Side Effects</td></tr></thead><tbody><tr><td>GLP-1 Receptor Agonists</td><td>15% - 21%</td><td>Mimics incretin hormones enhance insulin, suppresses glucagon</td><td>Nausea, vomiting, potential pancreatitis</td></tr><tr><td>Naltrexone/Bupropion</td><td>5% - 10%</td><td>Naltrexone reduces eating rewards; bupropion increases energy expenditure</td><td>Anxiety, depression, gastrointestinal symptoms</td></tr><tr><td>Endocannabinoid System Agents</td><td>5% - 10%</td><td>CB1 receptor antagonism</td><td>Psychiatric side effects, metabolic disturbances</td></tr><tr><td>Phentermine</td><td>5% - 10%</td><td>Central nervous system stimulant; appetite suppression</td><td>Increased heart rate, insomnia</td></tr><tr><td>Orlistat</td><td>5% - 10%</td><td>Lipase inhibitor; reduces fat absorption</td><td>Oily stools, gastrointestinal issues</td></tr></tbody></table>
**Combination Therapies:** Combination therapies have arisen as a strategic method in obesity treatment, particularly for patients who find it challenging to get sufficient weight loss with monotherapy. A prominent instance is the amalgamation of branded Contrave (Onakpoya et al., 2020, Roudbaraki et al., 2025). This dual-action medicine addresses various pathways related to weight regulation, rendering it a promising choice for holistic weight management. Naltrexone is primarily recognized as an opioid receptor antagonist. It inhibits the effects of opioids and other substances that stimulate the brain's reward pathways.

Naltrexone diminishes the pleasure derived from eating by obstructing reward pathways, especially in relation to high-calorie items commonly associated with cravings. This attenuation of the incentive effect may mitigate the desire to overconsume or select unhealthy food options. Bupropion: Bupropion operates as a norepinephrine and dopamine reuptake inhibitor, impeding the reabsorption of these neurotransmitters, which are integral to mood control and energy expenditure. Augmentation of Energy Expenditure: By potentiating dopamine transmission, bupropion increases motivational and locomotor activities, thereby indirectly accounting for higher energy expenditure. The stimulant-like effects boots metabolism and serves to elevate mood, which is mostly associated with hyperphagia (Grilo et al., 2023a). Efficacy Clinical trials have shown that the combination of naltrexone and bupropion results in a greater percentage of weight loss than monotherapy with either drug. Weight Loss Outcomes: In clinical trials, patients undergoing combination therapy achieved an average weight reduction of roughly 5% to 10% of their baseline body weight over the course of one year, when accompanied with a caloric deficit and enhanced physical activity. This result contrasts with the diminished efficacy rates often associated with single-agent therapy, highlighting the advantages of a multi-targeted strategy (Grilo et al., 2023b). Effective Weight Management: The integration of mechanisms targets both physiological and psychological dimensions of eating behavior, hence enhancing the likelihood of successful weight loss and maintenance in patients with obesity (Lyu et al., 2024). The combination of naltrexone and bupropion demonstrates potential efficacy; however, it entails certain safety risks that require scrutiny. may elevate the likelihood of neuropsychiatric adverse effects, such as anxiety, depression, and, in rare instances,

seizures. Individuals with a history of seizures or eating disorders are especially vulnerable and should exercise caution. Careful supervision is very important, especially at the beginning of treatment and while changing the dose. Patients must be instructed to promptly report any psychological alterations or atypical actions (Pi-Sunyer et al., 2019). Gastrointestinal Symptoms: Frequent adverse effects linked to combo therapy encompass nausea, constipation, vomiting, and xerostomia. Gastrointestinal symptoms may diminish with time as the body acclimatizes to the medicine. Cardiovascular Considerations: Caution is warranted in patients with a history of cardiovascular disease, as both drugs may affect cardiovascular function. Consistent surveillance of cardiovascular health is recommended for at-risk individuals. Contraindications: The combination therapy is contraindicated for people on opioid medicines, as the naltrexone component may induce withdrawal symptoms. Moreover, it is contraindicated for individuals with uncontrolled hypertension or for those who are pregnant or lactating (Onakpoya et al., 2020, Zehra et al., 2024).

**Anti-Obesity Agents Targeting the Endocannabinoid System:** The endocannabinoid system (ECS) is essential for regulating numerous physiological functions, such as appetite, metabolism, and energy homeostasis. The endocannabinoid system (ECS) is important for controlling many bodily functions, like hunger, metabolism, and energy balance. Anti-obesity drugs that affect the endocannabinoid system are getting more attention as possible treatments for obesity. These drugs predominantly interact with cannabinoid receptors (CB1 and CB2), affecting metabolic pathways associated with body weight management (Serefko et al., 2025). Mechanism of Action: Cannabinoid Receptors. The endocannabinoid system comprises two primary cannabinoid receptors: CB1 and CB2. CB1 receptors are predominantly situated in the brain and central nervous system, whereas CB2 receptors are primarily placed in peripheral tissues, such as adipose tissue and the immune system (Aloisio Caruso et al., 2025). Anti-obesity medicines that target the endocannabinoid system primarily interact with CB1 receptors in the brain, which play a crucial role in regulating appetite, food consumption, and the reward pathways linked to eating. Appetite Enhancement: Activation of CB1 receptors has been demonstrated to enhance appetite and
augment food consumption. Consequently, anti-obesity drugs aim to selectively block these receptors to diminish cravings and enhance fullness. By inhibiting the CB1 receptor, these drugs significantly reduce the reward response associated with food consumption, hence assisting in the mitigation of overeating and snacking tendencies. Metabolic Regulation: The ECS not only regulates hunger but also influences lipid metabolism and energy expenditure. Targeting the endocannabinoid system can regulate the storage and metabolism of lipids in the body (Lowe et al., 2021). Some anti-obesity drugs make white adipose tissue turn brown, which in turn facilitates the conversion of white fat into brown fat, which burns energy instead of storing it. This way, metabolic performance is enhanced. Impact on Insulin Sensitivity: The endocannabinoid system can influence the pathways that insulin signals. Anti-obesity drugs enhance metabolic health overall by blocking CB1 receptors, which makes insulin more sensitive and speeds up glucose breakdown and hence promotes improved overall metabolic health. Anti-obesity drugs Rimonabant is a well-documented CB1 receptor antagonist, which has been used as an anti-obesity drug acting through the endocannabinoid system. Although it has been withdrawn from the market market on grounds relating to safety, its mode of action is very informative on this mode of therapy. Safety Evaluation Targeting the endocannabinoid system offers potential for obesity management; however, it is essential to assess the safety profile of these therapies, particularly for previously utilized drugs. Psychiatric Adverse Effects: Rimonabant was associated with an increased risk of adverse psychiatric effects, including anxiety, depression, and suicidal ideation. This issue caused a lot of worry about whether CB1 antagonism was safe, especially for people who were at risk. Metabolic Effects: Some studies showed that lipid profiles got worse, with higher levels of triglycerides and LDL cholesterol. It is very important to keep an eye on these metabolic markers while giving these drugs (Dörnyei et al., 2023). while (Reddy et al., 2020, Akurati and Hanlon, 2025).

## 9. COMPARATIVE EFFECTIVENESS

When comparing the effectiveness of new weight reduction treatments to older ones, many scientific trials show that the new meds work better. Research indicates that contemporary medicines can lead to typical weight loss exceeding 15% of initial body weight in certain

instances, representing a significant advancement over previous treatments (Glass et al., 2019).

## 10. Conclusion

Obesity is a serious health issue today, which should be addressed through a multitude of approaches. Although dietary modifications, as well as physical exercises, are critical in this regard, people who suffer from severe cases of obesity require the help of medications as well. New developments in medications, specifically GLP-1 receptor agonists, as well as combination medications, have shown promise to combat substantial weight loss along with improved metabolic function. In order to combat the issues of obesity, as well as ensure a healthy future, it is essential to continue our research efforts in this area.

## CONSENT

It is not applicable.

## ETHICAL APPROVAL

It is not applicable.

## DISCLAIMER (ARTIFICIAL INTELLIGENCE)

Author(s) hereby declare that NO generative AI technologies such as Large Language Models (ChatGPT, COPILOT, etc) and text-to-image generators have been used during writing or editing of this manuscript.

## COMPETING INTERESTS

Authors have declared that they have no known competing financial interests or non-financial interests or personal relationships that could have appeared to influence the work reported in this paper.

## REFERENCES

Abdi Beshir, S., Ahmed Elnour, A., Soorya, A., et al. (2023). A narrative review of approved and emerging anti-obesity medications. *Saudi Pharmaceutical Journal*, *31*, 101757.
https://doi.org/10.1016/j.jsps.2023.101757

Akurati, S., & Hanlon, E. C. (2025). Beyond the scale: Exploring the endocannabinoid system's impact on obesity. *Current
*Diabetes Reports*, 25, Article 6.
https://doi.org/10.1007/s11892-024-01562-2

Albashir, A. A. D. (2020). The potential impacts of obesity on COVID-19. *Clinical Medicine (London)*, 20, e109–e113.
https://doi.org/10.7861/clinmed.2020-0239

Aloisio Caruso, E., De Nunzio, V., Tutino, V., & Notarnicola, M. (2025). The endocannabinoid system: Implications in gastrointestinal physiology and pathology. *International Journal of Molecular Sciences*, 26(3), Article 1306.
https://doi.org/10.3390/ijms26031306

Alsulami, S., Baig, M., Ahmad, T., et al. (2023). Obesity prevalence, physical activity, and dietary practices among adults in Saudi Arabia. *Frontiers in Public Health*, 11, 1124051.
https://doi.org/10.3389/fpubh.2023.1124051

Aragón-Martín, R., Gómez-Sánchez, M. D. M., Martínez-Nieto, J. M., et al. (2022). Independent and combined association of lifestyle behaviours and physical fitness with body weight status in schoolchildren. *Nutrients*, 14, Article 1208.
https://doi.org/10.3390/nu14061208

Ball, K., Timperio, A. F., & Crawford, D. A. (2006). Understanding environmental influences on nutrition and physical activity behaviors: Where should we look and what should we count? *International Journal of Behavioral Nutrition and Physical Activity*, 3, Article 33. https://doi.org/10.1186/1479-5868-3-33

Bays, H. E., Lazarus, E., Primack, C., & Fitch, A. (2022). Obesity pillars roundtable: Phentermine—Past, present, and future. *Obesity Pillars*, 3, 100024.
https://doi.org/10.1016/j.obpill.2022.100024

Bray, G. A., & Purnell, J. Q. (2022). An historical review of steps and missteps in the discovery of anti-obesity drugs. In *Endotext* (Internet). MDText.com, Inc.
https://www.ncbi.nlm.nih.gov/books/NBK278938/

Burke, L. K., Ogunnowo-Bada, E., Georgescu, T., et al. (2017). Lorcaserin improves glycemic control via a melanocortin neurocircuit. *Molecular Metabolism*, 6(9), 1092–1102.
https://doi.org/10.1016/j.molmet.2017.07.010

Collins, L., & Costello, R. A. (2024). Glucagon-like peptide-1 receptor agonists. In *StatPearls* (Internet). StatPearls Publishing.
https://www.ncbi.nlm.nih.gov/books/NBK551568/

Dörnyei, G., Vass, Z., Juhász, C. B., Nádasy, G. L., Hunyady, L., & Szekeres, M. (2023). Role of the endocannabinoid system in metabolic control processes and in the pathogenesis of metabolic syndrome: An update. *Biomedicines*, 11(2), Article 306.
https://doi.org/10.3390/biomedicines11020306

Fisman, E. Z., & Tenenbaum, A. (2021). The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: A novel cardiometabolic therapeutic prospect. *Cardiovascular Diabetology*, 20, Article 225.
https://doi.org/10.1186/s12933-021-01412-5

Ghusn, W., De la Rosa, A., Sacoto, D., et al. (2022). Weight loss outcomes associated with semaglutide treatment for patients with overweight or obesity. *JAMA Network Open*, 5(9), e2231982.
https://doi.org/10.1001/jamanetworkopen.2022.31982

Glass, J., Chaudhry, A., Zeeshan, M. S., & Ramzan, Z. (2019). New era: Endoscopic treatment options in obesity—A paradigm shift. *World Journal of Gastroenterology*, 25(32), 4567–4579.
https://doi.org/10.3748/wjg.v25.i32.4567

Grilo, C. M., Lydecker, J. A., & Gueorguieva, R. (2023). Naltrexone plus bupropion combination medication maintenance treatment for binge-eating disorder following successful acute treatments: A randomized double-blind placebo-controlled trial. *Psychological Medicine*, 53(15), 7775–7784.
https://doi.org/10.1017/S0033291723001800

Grilo, C. M., Lydecker, J. A., Jastreboff, A. M., Pittman, B., & McKee, S. A. (2023). Naltrexone/bupropion for binge-eating disorder: A randomized, double-blind, placebo-controlled trial. *Obesity*, 31(11), 2762–2773.
https://doi.org/10.1002/oby.23898

Henness, S., & Perry, C. M. (2006). Orlistat: A review of its use in the management of
obesity. Drugs, 66(12), 1625-1656.
https://doi.org/10.2165/00003495-200666120-00012

Hurt, R. T., Kulisek, C., Buchanan, L. A., & McClave, S. A. (2010). The obesity epidemic: Challenges, health initiatives, and implications for gastroenterologists. *Gastroenterology & Hepatology (New York)*, **6**, 780-792.
https://doi.org/10.1016/j.gastrohep.2010.10.001

Jensterle, M., Ferjan, S., & Janez, A. (2024). The maintenance of long-term weight loss after semaglutide withdrawal in obese women with PCOS treated with metformin: A 2-year observational study. *Frontiers in Endocrinology*, **15**, 1366940.
https://doi.org/10.3389/fendo.2024.1366940

Jin, X., Qiu, T., Li, L., et al. (2023). Pathophysiology of obesity and its associated diseases. *Acta Pharmaceutica Sinica B*, **13**, 2403-2424.
https://doi.org/10.1016/j.apsb.2023.01.012

Kamrul-Hasan, A., Alam, M. S., Dutta, D., Sasikanth, T., Aalpona, F. T. Z., & Nagendra, L. (2025). Tirzepatide and cancer risk in individuals with and without diabetes: A systematic review and meta-analysis. *Endocrinology and Metabolism*, **40**(1), 112-124.
https://doi.org/10.3803/EnM.2024.2164

Karrar, H. R., Nouh, M. I., Nouh, Y. I., et al. (2023). Tirzepatide-induced gastrointestinal manifestations: A systematic review and meta-analysis. *Cureus*, **15**.

Kokkorakis, M., Chakhtoura, M., Rhayem, C., et al. (2025). Emerging pharmacotherapies for obesity: A systematic review. *Pharmacological Reviews*, **77**, 100002.
https://doi.org/10.1124/pharmrev.123.001045

Lewis, K. H., Gudzune, K. A., & Ard, J. D. (2024). Phentermine in the modern era of obesity pharmacotherapy: Does it still have a role in treatment? *Current Obesity Reports*, **13**, 132-140.
https://doi.org/10.1007/s13679-023-00546-9

Li, Y., Gong, X., Găman, M. A., Hernández-Wolters, B., Velu, P., & Li, Y. (2024). The effect of subcutaneous dulaglutide on weight loss in patients with type 2 diabetes mellitus: Systematic review and meta-analysis of randomized controlled trials.

European Journal of Clinical Investigation, 54, e14125.
https://doi.org/10.1111/eci.14125

Louis, M., & Velazquez, E. (2025). The impact of new weight-loss medications on bariatric surgery and surgeon employment. *Cureus*, **17**, e83903.
https://doi.org/10.7759/cureus.83903

Lowe, H., Toyang, N., Steele, B., Bryant, J., & Ngwa, W. (2021). The endocannabinoid system: A potential target for the treatment of various diseases. *International Journal of Molecular Sciences*, **22**(17), Article 9472.
https://doi.org/10.3390/ijms22179472

Lundgren, J. R., Janus, C., Jensen, S. B., et al. (2021). Healthy weight loss maintenance with exercise, liraglutide, or both combined. *New England Journal of Medicine*, **384**(18), 1719-1730.
https://doi.org/10.1056/NEJMoa2028198

Lyu, Y. S., Ahn, H., Hong, S., & Park, C. Y. (2024). Safety and effectiveness of naltrexone-bupropion in Korean adults with obesity: Post-marketing surveillance study. *Drug Design, Development and Therapy*, **18**, 5255-5268.
https://doi.org/10.2147/DDDT.S492913

Mitchell, N. S., Catenacci, V. A., Wyatt, H. R., & Hill, J. O. (2011). Obesity: Overview of an epidemic. *Psychiatric Clinics of North America*, **34**, 717-732.
https://doi.org/10.1016/j.psc.2011.08.005

Młynarska, E., Bojdo, K., Bulicz, A., et al. (2025). Obesity as a multifactorial chronic disease: Molecular mechanisms, systemic impact, and emerging digital interventions. *Current Issues in Molecular Biology*, **47**, Article 100787.
https://doi.org/10.3390/cimb47100787

Moiz, A., Filion, K. B., Tsoukas, M. A., Yu, O. H., Peters, T. M., & Eisenberg, M. J. (2025). Mechanisms of GLP-1 receptor agonist-induced weight loss: A review of central and peripheral pathways in appetite and energy regulation. *The American Journal of Medicine*. Advance online publication.
https://doi.org/10.1016/j.amjmed.2025.01.021

Molina, K., Baskin, M. L., Long, D., & Carson, T. L. (2021). Psychological and behavioral pathways between perceived stress and weight change in a behavioral weight loss intervention. *Journal of Behavioral Medicine*, **44**, 822-832.
https://doi.org/10.1007/s10865-021-00231-z

Olukorode, J. O., Orimoloye, D. A., Nwachukwu, N. O., et al. (2024). Recent advances and therapeutic benefits of glucagon-like peptide-1 (GLP-1) agonists in the management of type 2 diabetes and associated metabolic disorders. *Cureus*, *16*, e72080.
https://doi.org/10.7759/cureus.72080

Onakpoya, I. J., Lee, J. J., Mahtani, K. R., Aronson, J. K., & Heneghan, C. J. (2020). Naltrexone-bupropion (Mysimba) in management of obesity: A systematic review and meta-analysis of unpublished clinical study reports. *British Journal of Clinical Pharmacology*, *86*(4), 646–667.
https://doi.org/10.1111/bcp.14210

Pirtle, J. L., Hickman, M. D., Boinpelly, V. C., Surineni, K., Thakur, H. K., & Grasing, K. W. (2019). The serotonin-2C agonist lorcaserin delays intravenous choice and modifies the subjective and cardiovascular effects of cocaine: A randomized, controlled human laboratory study. *Pharmacology Biochemistry and Behavior*, *180*, 52–59.
https://doi.org/10.1016/j.pbb.2019.02.010

Pi-Sunyer, X., Apovian, C. M., McElroy, S. L., Dunayevich, E., Acevedo, L. M., & Greenway, F. L. (2019). Psychiatric adverse events and effects on mood with prolonged-release naltrexone/bupropion combination therapy: A pooled analysis. *International Journal of Obesity*, *43*(10), 2085–2094.
https://doi.org/10.1038/s41366-018-0302-z

Reddy, V., Grogan, D., Ahluwalia, M., et al. (2020). Targeting the endocannabinoid system: A predictive, preventive, and personalized medicine-directed approach to the management of brain pathologies. *EPMA Journal*, *11*(2), 217–250.
https://doi.org/10.1007/s13167-020-00203-4

Roudbaraki, S. N., Salimi, M., Esmailpour, S., & Mohammadi, F. (2025). Efficacy of naltrexone and bupropion combination in patients with binge eating disorder: A systematic review and meta-analysis. *Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity*, *30*, Article 75.
https://doi.org/10.1007/s40519-025-01786-5

Ryan, D. H., & Yockey, S. R. (2017). Weight loss and improvement in comorbidity: Differences at 5%, 10%, 15%, and over. *Current Obesity Reports*, *6*, 187–194.
https://doi.org/10.1007/s13679-017-0262-y

Samms, R. J., & Sloop, K. W. (2025). A contemporary rationale for agonism of the GIP receptor in the treatment of obesity. *Diabetes*, *74*(8), 1326–1333.
https://doi.org/10.2337/dbi24-0026

Serefko, A., Lachowicz-Radulska, J., Jach, M. E., Świąder, K., & Szopa, A. (2025). The endocannabinoid system in the development and treatment of obesity: Searching for new ideas. *International Journal of Molecular Sciences*, *26*(19), Article 9549.
https://doi.org/10.3390/ijms26199549

Tak, Y. J., & Lee, S. Y. (2021). Anti-obesity drugs: Long-term efficacy and safety—An updated review. *World Journal of Men's Health*, *39*, 208–221.
https://doi.org/10.5534/wjmh.200010

Vijayashankar, U., Ramashetty, R., Rajeshekara, M., et al. (2024). Leptin and ghrelin dynamics: Unraveling their influence on food intake, energy balance, and the pathophysiology of type 2 diabetes mellitus. *Journal of Diabetes and Metabolic Disorders*, *23*, 427–440.
https://doi.org/10.1007/s40200-024-01418-2

Wang, L., Wang, Q., Xiong, Y., Shi, W., & Qi, X. (2025). Obesity and its comorbidities: Current treatment options, emerging biological mechanisms, future perspectives and challenges. *Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy*, *18*, 3427–3445.
https://doi.org/10.2147/DMSO.S540103

Westbury, S., Oyebode, O., van Rens, T., & Barber, T. M. (2023). Obesity stigma: Causes, consequences, and potential solutions. *Current Obesity Reports*, *12*, 10–23.
https://doi.org/10.1007/s13679-023-00495-3

Zehra, S., Saeed, M. A., Zaman, M., & Hassan, S. (2024). High-performance liquid chromatography-based analytical techniques for simultaneous determination of naltrexone hydrochloride and bupropion hydrochloride: A comprehensive review. *Discover Applied Sciences*, *6*, Article 229.
Zile, M. R., Borlaug, B. A., Kramer, C. M., et al. (2025). Effects of tirzepatide on the clinical trajectory of patients with heart failure, preserved ejection

fraction, and obesity. *Circulation*, **151**(9), 656–668.

https://doi.org/10.1161/CIRCULATIONAHA.124.072679

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