INTRODUCTION:

Obesity is one among the most serious problem prevailing in the present world. It is almost triple since 1975 according to WHO¹. All the types of population and age groups are affected by this problem in one way or the other. The main reason for improper and delayed treatment of obesity is its identification, diagnosis and financial prospect. It’s very difficult to treat obesity because it is misleading with the term healthy. BMI is the main criteria to detect and specify that the patient is obese. However, lack of knowledge about BMI in population is the key factor in identifying obesity. According to WHO; “BMI (body mass index) is defined as a person’s weight (in kilograms) divided by the square of his or her height (in metres)”. A person with a BMI of 30 or more is generally considered obese. A person with a BMI equal to or more than 25 is considered overweight². Many Researchers in the past have work on obesity and its associated comorbidities^3-20. The present review work tries to emphasize on the Economical prospect of obesity medications. The value of BMI through which the obesity is specified is presented in Table 1.

Table 1 Classification of Body Weight Status Based on BMI²¹

Body Weight Status	BMI Value
Underweight	Less than 18.5
Healthy Weight	Between 18.5 and 25
Overweight	Between 25 and 30
Obese	Between 30 and 40
Extremely Obese/Morbidly Obese	Above 40

Economical aspect of obesity is the major hindrance in the proper and appropriate treatment. The treatment of obesity can be done in many ways. Current treatment strategies (Table 2) available for the treatment of obesity are being identified and specified by many researchers all over the world. Some treatments involve removal of lipids by surgery, some includes treatment through hormonal therapy or even electroconvulsive therapy. All these procedures are economically costly which are unbearable by all patients.

Table 2: Details of Different Therapies for Obesity^22-27

Therapies	Working Approach of Therapy
Allopathy	Direct use of the medicine to prevent and dissolve the excess of deposited fats in tissues and muscles.
Ayurvedic	In obese persons, digestive fire may be optimum. To improve its power, herbs chitraka, karanja, neem, rohitaka, shinshipa, apaamarga, brahmi, bilwa are used.
Behavioral therapy/ Psychotherapy	Reduces the peer pressure related to surgery and weight loss diet pattern follow-ups
Chinese therapy	Acupuncture
Electroconvulsive therapy	Often used for depression but in recent years showed significant weight loss in obese patients
Gene therapy	It increases or decreases gene product and restore and maintain energy homeostasis.
Homeopathic	It role is bit similar to Ayurveda, but instead of herbs the crude extracts are used
Naturopathy	It focus less on diet and try to correct underlying imbalance through life style change and proper planning

There are large numbers of drugs which are being used in the treatment of obesity. The mechanism of action of each drug is different including Phentermine, Diethylpropion, Fluoxetine (Reducing food intake); Orlistat (Reducing fat absorption); Lorcaserin (Selective 5‑HT2C receptor agonist); Metformin (Antidiabetic). Many of the drugs under this category of anti-obesity are either withdrawn from the market or are not being approved as anti-obesity agent. The adverse effects of the drugs or patients non-compliance can be one among the prominent reason for the same.

Table 3 Specifies the Current Status of Anti-Obesity Agents Along with Its Mechanism Of Action²⁸.

S. No.	Drugs	Brand Name	Current status	Mechanism of Action
I.	Aminoxaphen	Aminorex	Withdrawn	Indirect sympathomimetic action
II.	Amphetamine	Evekeo Adzenys XR‑ODT Dyanavel XR	Banned as an anti‑obesity drug	Increases the neurotransmitters dopamine, noradrenaline, and serotonin in brain
III.	Bupropion+naltrexone	Contrave	Still under investigation	Bupropion increases the activity of POMC neurons. Naltrexone blocks opioid receptors on the POMC neurons, preventing feedback inhibition and increasing POMC activity
IV.	Cetilistat	Cetislim	Not approved	Lipases inhibitor
V.	Diethylpropion	Tenuate Tepanil	Short‑term use (<12 weeks)	Reducing food intake
VI.	Dinitrophenol	Dinitriso Nitromet Dinitrenal	Withdrawn	Uncouples oxidative phosphorylation in mitochondria
VII.	Fenfluramine, dexfenfluramine	Pondimin Redux	Withdrawn	Selective serotonin reuptake inhibitor
VIII.	Fluoxetine	Prozac Sarafem	Short‑term use (<12 weeks)	Reducing food intake: Selective serotonin reuptake inhibitor
IX.	Lorcaserin	Belviq	Recently approved	Selective 5‑HT2C receptor agonist
X.	Orlistat	Xenical	Marketed	Reducing fat absorption: Lipase inhibitor
XI.	Phentermine	Adipex‑P Lonamin	Short‑term use (<12 weeks)	Reducing food intake: Sympathomimetic amine
XII.	Phenylpropanolamine	Accutrim Dexatrim	Banned in the USA	Central α₁‑adrenergic receptor agonist
XIII.	Rimonabant	Acomplia	Withdrawn	Reducing food intake: Selective CB1 receptor blocker
XIV.	Sibutramine	Meridia	Withdrawn	Reducing food intake: Combined norepinephrine and serotonin reuptake inhibitor
XV.	Tesofensine	‑	Not approved	Norepinephrine, dopamine and serotonin reuptake inhibition
XVI.	Topiramate+phentermine	Qsymia	Recently approved	Topiramate blocks voltage‑dependent sodium channels, glutamate receptors and carbonic anhydrase, and augments GABA activity; phentermine is sympathomimetic

Economical Aspect of Anti-obesity Medication:

Economically the anti-obesity medication is very heavy on the pockets of the patients. Most of the anti-obesity formulations have to be utilized by the patients over the long period. Also the cost of almost each drug is quite high. Since, this heavy cost and long therapy scheduled sometimes resulted in non-compliances among the patients. Moreover, the sedentary lifestyle and inappropriate eating schedule boost the obesity and prolongs the treatment schedule. Some drugs with cost are being specified in Figure 1 which supports the prospects that it is very difficult for economically weaker section to procure the same.

Figure 1: Approximate Prices (per 30 tabs/caps) in INR²⁹

There are large numbers of side effects with anti-obesity medication in association to its pharmacological role. These side effects have lead to the withdrawal of many drugs under this category. This resulted in limited numbers of marketed availability of anti-obesity preparations. Higher side effects and discontinuation of some drugs have pilot the prices of other available drugs.

Table 4: specifies the side effects of drugs which are being withdrawn or not approved.

S. No.	Drug	Side Effects
	Aminorex³⁰	Insomnia Restlessness Proteinuria Seizures Hyperreflexia Respiratory Depression Mydriasis Tachycardia Hypertension Hyperpnea
1.	Amphetamine³¹	Low Or High Blood Pressure Raynaud’s Phenomenon, Where There Is Reduced Blood Flow to The Extremities Erectile Dysfunction, And Especially Frequent or Persistent Erections Rapid Heart Rate Abdominal Pain Loss of Appetite, Nausea, And Weight Loss Acne, Rash, Hives Blurred Vision and Dry Mouth Teeth Grinding Nosebleed Profuse Sweating Nasal Congestion Increased Likelihood of Seizures for Susceptible Individuals Tics Faster, Deeper Breaths, Especially in Those with Other Lung Conditions Difficulty Urinating Increased Alertness and Focus Apprehension, Anxiety, Irritability, And Restlessness Mood Swings Insomnia Changes in Libido Grandiosity, Or an Exaggerated Sense of One’s Own Importance Obsessive Behaviors Effects on Child Growth
2.	Contrave³²	Nausea, Headache, Vomiting, Constipation, Diarrhea, Dizziness, Trouble Sleeping (Insomnia), Dry Mouth, Anxiety, Hot Flashes, Fatigue, Tremor, Abdominal Pain, Flu Symptoms, Ringing in The Ears, Urinary Tract Infection, High Blood Pressure, Increased Sweating, Changes in Taste, Rash, Muscle Strain, Palpitations, Problems with Attention, Lightheadedness/ Fainting.
3.	Cetilistat³³	Headache Nausea or Vomiting Unusual Tiredness or Weakness Tooth Problems Trouble with Sleeping Itching and Skin Rash Yellow Colored Eyes or Skin Abdominal Pain and Discomfort Abnormal Bowel Movements Difficulty in Breathing Dark Colored Urine Loss of Appetite
4.	Nitromet³⁴	Bluish-Colored Lips, Fingernails, Or Palms Blurred or Loss of Vision Bulging Soft Spot on The Head of An Infant Change in Consciousness Change in The Ability to See Colors, Especially Blue or Yellow Cold, Clammy Skin Dark Urine Difficulty Breathing Disturbed Color Perception Dizziness or Lightheadedness Double Vision Fever Flushed Skin Halos Around Lights Headache, Severe and Throbbing Increased Sweating Loss of Appetite Loss of Consciousness Night Blindness Overbright Appearance of Lights Pale Skin Paralysis Slow Or Irregular Heartbeat Sore Throat Tunnel Vision Unusual Bleeding or Bruising Unusual Tiredness or Weakness
5.	Redux³⁵	Taste Abnormalities and Amblyopia Abnormal Vision, Conjunctivitis, Eye Disorder, Glaucoma, Dry Eyes, And Mydriasis Alopecia, Sweating, Urticaria, And Pruritus. Lymphadenopathy, Polycythemia And Thrombocytopenia Hypoglycemia And Hypokalemia Pharyngitis
6.	Dexatrim³⁶	Hemorrhagic Stroke Tremor, Anxiety, Insomnia, Dizziness Bipolar Disorder Interstitial Nephritis
7.	Acomplia³⁷	Psychological Adverse Effects Suicidality Depression
8.	Meridia³⁸	Tourette's Syndrome Hypesthesia Decreased Libido Increased Libido Mood Changes Nightmares Short Term Memory Loss Speech Disorder Transient Ischemic Attack Tremor Twitch Vertigo Seizures

CONCLUSION:

The present work suggested that there are numbers of anti-obesity drugs which are being withdrawn from the market in the past. Some drugs promises to be better anti-obesity apart from its other counterparts. Numerous sides’ effects of many anti-obesity agents are the major reason of its withdrawal. However, the high prices of the drugs along with long term therapy with medication have further boosted the cause of withdrawal. Hence it is suggested that the economical aspect of the drugs needs to be monitored for better further prospect of anti-obesity medications.

CONFLICT OF INTEREST:

There are no conflicts of interest.

REFERENCES:

1. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

2. https://www.who.int/topics/obesity/en/

3. Segula D. Complications of obesity in adults: A short review of the literature. Malawi Med J. 2014; 26(1): 20–24.

4. Oh T.J. The Role of Anti-Obesity Medication in Prevention of Diabetes and Its Complications. J Obes Metab Syndr. 2019; 28(3):158-166

5. Sahu R.K, Prashar D. Current Treatment Strategies for Obesity Including Indian Scenario. Asian J Pharm. 2016 (Suppl); 10 (3): S342-S349.

6. Sahu R.K, Prashar D. Efficacy of Metformin in Obese young people In Secondary care: A Systematic Review and Meta-Analysis from Randomized Controlled Trials. Int J Chemtech Res. 2017;10(10): 356-360.

7. Theodoulou A, Krishnan J, Aromataris E. Risk of complications in patients who are obese following upper limb arthroplasty: A systematic review and meta-analysis. Obes Res Clin Pract. 2020;14(1): 9-26.

8. Prashar D, Sahu R.K. A Methodological Analysis on Obesity. Int J Life Sci Scienti Res 2015; 1(1): 12-14.

9. Kumar DB, Chand S, Parashar B, Sharma D, Dhamija H. Effect of Obesity on Fertility in Women with Polycystic Ovary Syndrome. Asian J Res Pharm Sci. 2011; 1(4): 127-130.

10. Chandrakala M. Lifestyle Modification to Combat Adolescent Obesity. Asian J Nur Edu Res 2011; 1(3): 82-84.

11. Anilkumar B, Jarali G, Radhakrishnan. Stress, Obesity and Selected Health Problems among Professionals. Asian J Nur Edu Res 2013; 3(3): 154-163.

12. Edna Sweenie J. A New Approach to Assess the Health Benefits of Obesity Prevention Interventions among School Children in Chennai, Tamilnadu. Asian J Nur Edu Res 2013; 3(4): 216-218.

13. Balakrishnan P, Sharma S, Chandrakar R. A Descriptive Survey to Assess the Knowledge of School Children Regarding Obesity and its Complication in selected School at Raipur. Asian J Nur Edu Res 2013; 3(4): 237-239.

14. Thressia P.A, Kumar R. Effect of Sleep Duration on Obesity and the Glycemic level in Patients with Type 2 Diabetes. Asian J Nur Edu Res 2014; 4(4): 502-507.

15. Khan M.Y, Gupta P, Bihari B, Verma V.K. A Review on Diabetes and Its Management. Asian J Pharm Res 2013; 3(1): 27-32.

16. Mewada P.S, Patel C.K, Rami C.S, Patel H.U, Patel C.N. New Emerging Targets for Obesity. Asian J Res Chem 2010; 3(2): 278-287.

17. Radhakrishnan S.A. Advanced Maternal Weight. Int J Adv Nur Management 2016; 4(2): 153-160.

18. Tripathi K. Herbs for Obesity: A Review. Res J Pharmaco Phytochem 2009; 1(2): 103-108.

19. Prashar D, Saklani S. Pharmaceutical and Economical Aspects of Medicinal Herbs: An Overview. Res J Pharmaco Phytochem 2011; 3(5):187-190.

20. Vyasa B. Obesity in India – The Omnipresent Influence. Res J Pharmaco Pharmacodyn 2013; 5(4). 220-226.

21. National Heart, Lung, and Blood Institute. Guidelines on over-weight and obesity: the electronic textbook. Assessment of weight and body fat.

22. Fujioka K, Lee M.W. Pharmacologic Treatment Options for Obesity: Current and Potential Medications. Nutr Clin Prac 2007; 22(1):50–54.

23. Kaplan L.M. Pharmacological Therapies for Obesity. Gastroent Clin North Am 2005; 34(1): 91–104.

24. Koithan M, Sutherland E. Naturopathic Treatment of Obesity. J Nur Practi 2009; 5(9): 693-694.

25. Eldor J, Kotlovker V, Kotlovker S. Electroconvulsive Therapy for Obesity Treatment. Open J Anesth 2014; 4:68-71.

26. Jacob J.J, Isaac R. Behavioral Therapy for Management of Obesity. Ind J Endo Met 2012; 16(1):28-32.

27. Gao M. Gene Therapy for Obesity: Progress and Prospect. Dis Med 2014; 17(96); 319-328.

28. Li M, Cheung B.M. Pharmacotherapy for Obesity. Br J Clin Pharmacol 2009; 68:804-810.

29. https://www.medindia.net/drug-price/brand

30. Hadler A.J. Studies of Aminorex, A New Anorexigenic Agent. J Clin Pharmacol J New Drugs 1967; 7(5):296–302.

31. https://www.medicalnewstoday.com/articles/221211#risks

32. https://www.rxlist.com/contrave-side-effects-drug-center.htm

33. https://www.practo.com/medicine-info/cetilistat-2139-api#side-effects

34. https://www.drugs.com/sfx/nitro-par-side-effects.html

35. https://www.drugs.com/sfx/redux-side-effects.html

36. https://www.drugs.com/sfx/dexatrim-side-effects.html

37. https://www.drugs.com/sfx/acomplia-side-effects.html

https://www.drugs.com/sfx/meridia-side-effects.html