The Current Market of Pharmacological Drugs for the Prevention and Treatment of Obesity in Ukraine: A Review

ABSTRACT

https://jbcpm.com/ others rehabilitation programs, methods and techniques of therapy of patients of different ages, genders and profiles are presented.A large number of scientists in their publications focus on the problematic aspects of modern prevention and treatment of obesity at different ages (Wolfe et al., 2016;Rooney et al., 2014;Ianosi et al., 2015;Arrebola et al., 2011;Armstrong, Bolling, Michalsky et al., 2019).Experts in the field of obesity and overweight have conducted numerous studies.With the help of drugs that meet the requirements of evidence-based medicine (EM), there is a constant search for promising methods of reducing body weight and methods of obesity treatment.Mostly in review publications, medicines are considered only from the standpoint of means that can help the patient to improve quality of life (Manouchehri et al. 2022;Oboodiat et al., 2021;Manouchehri, 2023).They act as objects of the pharmacotherapeutic process.The analysis of the modern market of pharmacological drugs for the prevention and treatment of obesity from the standpoint of evidence-based medicine and the impact on quality of life was conducted only in separate publications.This is the relevance of this publication.The purpose of the study was to analyze the availability of developed anti-obesity drugs on the pharmaceutical market of Ukraine, their availability to a wide range of consumers, and therapeutic effectiveness.

Methods
The research materials published data from various sources of information on the availability of drugs and methods of treatment of obese patients and used the analytical search method of modern information systems.We conducted an analysis of the modern market of drugs for the treatment and prevention of obesity.The objects of the study were search databases of evidence-based medicine, the website of the Ministry of Health of Ukraine and others.Information about the real state of registration and a certain level of evidence of therapeutic effectiveness, pharmacological safety of drugs for the treatment and prevention of obesity was of particular interest.The basis of modern evidence-based medicine is the Cochrane collaboration; PubMed database (MEDLINE); database of abstracts of effects (DARE); Medscape.An analysis of the State Register of Medicinal Products of Ukraine was also conducted.

Results and Discussion
The analysis showed that in the 1930s, laxatives were actively used for weight loss: Medilax (Purgen) (the active substance is Phenolphthalein).As stated in the publication of Andriychuk, Smetanina et al. (2022), the implementation and use of Purgen is currently suspended and prohibited.
In the 1950s, Ethylamphetamine (Adiparthrol, Apetinil, Ethamphetamine) was preferred in the treatment of obesity.It is currently not approved for use in the US, EU due to confirmed extreme toxicity (Bluher 2019, Garvey et al., 2014).On the pages of Evidence-based Medicine Sites, information is provided that in the 1970s, drugs included in the group "A08 Drugs for the treatment of obesity (except dietary products)" and those with separate ATC codes were used to treat obesity: Katyn (Alvalin, Anti-adiposit X112T, ReliSlim) -prohibited in the EU, USA, CIS countries; Clobenzorex (Asenlix, Dinintel, Finedal, Itravil, Obeclox, Rexigen) -prohibited in the EU, USA, CIS countries, permitted for use in Mexico and Latin America; Mefenorex (Pondinil, Rondimen) is prohibited in the EU, the USA, the CIS countries due to a large number of side effects up to the development of a fatal outcome.The publication of Klymyshina and Smetanina (2018) and Andriychuk et al., (2021) also considers these issues.In the protocols of the pharmacist (2014), it is noted that modern drugs for the treatment of obesity belong to groups А08АА (drugs of central action), А08АВ (peripheral action), and А08АН (others) according to the ATS classification (Table 1).According to Safaei et al., 2021, Smetanina (2009), and other, there are many other groups, but they are mainly auxiliary or supportive therapy.It is worth noting that most drugs intended for the prevention and treatment of various stages of obesity show the effect of tolerance and the possible development of dependence on them.In addition, almost all drugs for weight loss, except for Xenical, are included in the list of "regulated substances".Slimming drugs have side effects, most of which are minor (some may be unpleasant) and usually disappear over time as the body adapts to pharmacotherapy.In some cases, serious complications with the development of fatal outcome are possible.There are restrictions on the use of all weight loss drugs, especially for the elderly and children.Therefore, the use of such drugs is controlled, prescribed by a doctor and self-medication without consulting a family doctor is prohibited.Ukraine has a legally approved EU integration strategy, which provides for measures to harmonize the regulatory framework, in particular the system of standardization and certification of medicines in Ukraine, with EU standards and directives.In the pharmaceutical industry, such harmonization makes it possible to increase the level of quality assurance of drugs, to unify requirements for registration and licensing.The main requirements for drugs are quality, efficiency, safety.This fact is shown in the publications of the author of this post in different years (Smetanina 2010(Smetanina , 2019)).All medicinal products (drugs) in circulation in Ukraine must meet the requirements of global quality indicators: Pharmaceutical Development, Standards of Good Practice (GLP, GCP, GRP, GMP, GSP, GDP, and GPP), Good Practices of the pharmacological supervision of safety and efficacy.Recently, a medical approach to the tactics of managing patients, built on the principles of evidence-based medicine, has become widespread.The Pharmaceutical Encyclopedia and the pages of the Pharmaceutical Wikipedia call EBM medicine that is based on available evidence of the effectiveness and safety of drugs that have undergone a pharmacoepidemiological study using mathematical estimates of the probability of success and risk.A number of authors emphasize this in their publications: Finer et al., 2000, Ball et al., 2009, Hung et al., 2015, Bauer et al., 2020 and others.The analysis of published experiments on the internet are presented https://jbcpm.com/ in Table 2.We conducted an analysis of sources of evidence, which revealed that for the treatment and prevention of obesity at the present stage, the following drugs are used: -Orlistat (Xenical, Alli): Proven effectiveness of the drug in weight loss by 2% more than placebo in the period from 4 to 24 months of use.In 2010, the Food and Drug Administration (FDA) conducted a safety review of Orlistat for reports of liver dysfunction in a small number of people taking it.In order to prevent disorders that may indicate liver damage, it is recommended to use Xenical or Alli as a substitute for Orlistat.Available over-the-counter in small doses in the United States.Not registered in Ukraine.
-Lorcaserin (Belvik): It is a drug for complex therapy, blocks the urge to starve, allowing patients to feel full with minimal food intake.Registered in the United States in 2012.Recommended by the FDA for longterm use.Belvik was rejected by the FDA at the beginning of the implementation (fears were based on the fact that its principle is similar to Fenfluraminewhich was withdrawn from the market due to adverse effects on heart valves), but later manufacturers provided additional research data permission to sell.There is no reliable evidence that Belvik worsens the condition of the heart valve.The FDA requires manufacturers to develop medical strategies for risk assessment and response strategies (REMS).Prescription drug (USA).Subject to control under the Controlled Substances Act.Federal law prohibits unauthorized sale or transfer to third parties.There is no registration in Russia.Not registered in Ukraine.
-Phentermine (Adipex): It is a drug of short-term use (not more than 12 months).The pharmacological action of the drug is the release of norepinephrine, which suppresses appetite.According to the All-Ukrainian Gastroenterological Organization (UGO) it is established that the use of Phentermine increases the patient's weight loss by 3-4% compared with placebo.Proven risk of Phentermine dependence (classified by the Drug Enforcement Agency, USA, as a controlled substance under Scheme IV).FDA-approved Phentermine brands: Adipex-P, Oby-Cap, Suprenza, T-Diet, Zantryl.In the United States, it is a prescription drug.It's circulation is regulated by the Federal Controlled Substances Act.It is not allowed to be used in many European countries.Included in the "List of narcotic drugs, psychotropic substances and their precursors subject to control."Subject to subjectquantitative accounting in Russia.Not registered in Ukraine.
-Topiramate: It is an antiepileptic drug used in obesity in patients with bipolar disorder.The UGO has been studied for a long time.The following Topiramate brands are represented in the United States: Topamax, Topamax Sprinkle, Topiragen.In February 2012, the drug Qsymia (Xymia) with the complex active ingredient Phentermine + Topiramate was registered in the United States.Xymia increases the risk of birth defects in the fetus of the patient who took this drug.In this regard, the FDA requires manufacturers to develop risk assessment and response strategies.Ximia is a prescription drug for the United States.In Russia, there is no drug with the active substance Phentermine (single drug or complex drug).Prohibited for use since 2009.Since February 2013, Xymia has been denied registration by the European Medicines Agency due to the possibility of developing heart attack during treatment.The drug has been banned from use in the EU and Ukraine since 2013.-Sibutramine (Meridia): It is an inhibitor of the reversal of serotonin and norepinephrine, the only drug that physiologically neutralizes the root cause of fat deposits.
-increases energy expenditure and gives a feeling of satiety.According to the UGO, taking 1 capsule a day helps to lose 5% or more weight than placebo.Sibutramine was approved in 1997 as a drug for weight loss, but in 2010, its sale on the market was limited, as studies have shown an increased risk of serious heart complications, including of myocardial infarction and stroke.In the United States, Sibutramine is subject to control under the Controlled Substances Act.In late 2010, the Meridia brand was recalled at the request of the FDA.In Russia, drugs that contain Sibutramine as an active substance (Goldline, Lindaxa, Meridia, Slimia, Reduxin) are subject to subjectquantitative accounting.In 2011, it was banned in most EU countries.Not registered in Ukraine.
- In studies conducted by the FDA, it was shown that the background of the drug significantly reduces the incidence of psychogenic overeating compared with placebo.In 2015, Lisdexamphetamine in the form of Lisdexamphetamine dimesilate was officially registered with the FDA under the name Vyvanse for the treatment of bulimia (psychogenic overeating).When analyzing treatment schemes for patients with various manifestations of obesity according to the Pharmacist's Protocol, it was established that a wide range of over-the-counter drugs, including diuretics, can be dispensed for the treatment of obesity.But the latter should be used with caution and only in case of swelling, because their overdose can provoke kidney failure.There are data on the use of Thyroxine for weight loss in patients with normal thyroid function.However, the use of the latter is potentially dangerous, especially with heart disease.Therefore, it is prescribed only when hypothyroidism and obesity are concomitant pathologies.Dalle Grave et al., 2013, Hruby and Hu 2015, Nuttall 2015, Vasendin 2015, De Lorenzo et al., 2019, Davoudi 2021 and many other authors confirm that there is a wide range of drugs that can be offered to a patient to prevent obesity.However, when using overthe-counter drugs, in order to avoid the consequences of self-medication, you should consult a specialist who will help you understand the advantages and disadvantages of individual drugs, taking into account the individualization of pharmacotherapy.Using the experience of colleagues (Heber, 2003;De Lorenzo et al., 2019;Apovian, 2016;Safaei et al., 2021), we analyzed the herbal medicine market in order to study the existing dosage forms and types of drugs for prevention and treatment of obesity (Shapovalova 2018), but they are the subject of another publication.

Conclusions
We conducted an analysis and studied the main range of modern drugs, analyzed their evidence base, trade synonyms and the state of use in different countries.The study can be used to further develop modern drugs for weight loss with a wide therapeutic range, easy tolerability, and high efficiency and availability groups of overweight patients.

Conflict of interest
There are no conflicts of interest.

Table 1 .
ATC classification of drugs for the treatment of obesity ATC

Table 2 .
The main sources of evidence-based medicine (EBM)

Institute for Health and Clinical Excellence Baseline
Clinical Guidelines of the National Institutes of Health and Quality of Care in the United Kingdom According to the UGO, daily single use of Diethylpropion at a dose of 75 mg increases the patient's weight loss by 3-4% compared with placebo.FDA approved for short-term use only -up to 12 weeks.Brands and generics of Amfepramon approved in the United States: Tepanil, Diethylpropion hydrochloride.In the United States -a prescription drug.The Controlled Substances Act regulates the circulation of the drug.In Russia, it belongs to the II list of narcotic drugs and psychotropic substances with restricted circulation and state control of circulation.Not allowed sale.It is banned in the EU.Not registered in Ukraine.
period of dynamic monitoring after treatment.-Fenfluramine(Pondimin): It increases the feeling of satiety due to increased levels of serotonin in the brain.In the late 1990s, it was discovered that even small doses of Fenfluramine, especially in combination with Phentermine, could cause pulmonary hypertension and heart valve disease.Therefore, in the United States, the Controlled Substances Act is included in the CIV list and its sale or federal law governs transfer to third parties.Not registered in Ukraine.
anxiety, nausea, diarrhea, suicidal ideation and suicide).Brand names: Zimulti, Acomplia, Bethin, Monaslim, Remonabent, Riobant, Slimona, Rimoslim, Riomont.In Russia, the drug with the active substance Rimonabant (Zimulti) was approved for use until 2009.Not registered in Ukraine.The drug is in new stages of research.Requires a number of qualitative studies with a long