Obesity nowadays affects an increasing number of people. We can talk about it when the patient's BMI is ≥ 30.0 kg/m² (BMI 25.0-29.9 kg/m² - overweight). While obesity in itself may not be a problem for people suffering from it, its complications can be global and sometimes pose a serious threat to health or even life. Its main complications in the cardiovascular system include: hypercholesterolaemia, arterial hypertension, left ventricular hypertrophy, early atherosclerotic changes, heart and cerebral infarction. Treatment of obesity is based mainly on changing the patient's lifestyle - diet and physical activity, which can sometimes be problematic and difficult to apply.
However, there is a new group of hypoglycaemic drugs - glucagon-like peptide-1 (GLP-1) agonists, which can make obesity treatment easier. These drugs use the incretin effect in the body to increase insulin secretion in response to a meal containing carbohydrates and prevent postprandial hyperglycemia. In this article, we will analyze the latest studies on the effects of GLP-1 receptor agonists, using semaglutide as an example, on the cardiovascular system and on weight loss in patients

Bielewicz, Krzysztof

Chmura, Anna

Karaś, Anna

Kawałko, Kinga

Pondel, Kamil

English

Akademicka Platforma Czasopism

55Pondel Kamil, Kawałko Kinga, Bielewicz Krzysztof, Chmura Anna, Karaś Anna. Effect of glucagon-like peptide-1 (GLP-1) agonistson the example of semaglutide on the cardiovascular system and their role in the treatment of obesity. Journal of Education, Healthand Sport. 2022;12(9):55-60. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2022.12.09.007https://apcz.umk.pl/JEHS/article/view/JEHS.2022.12.09.007https://zenodo.org/record/7029272The journal has had 40 points in Ministry of Education and Science of Poland parametric evaluation. Annex to the announcement of the Minister of Education and Science of December 21, 2021. No. 32343.Has a Journal's Unique Identifier: 201159. Scientific disciplines assigned: Physical Culture Sciences (Field of Medical sciences and health sciences); Health Sciences (Field of Medical Sciences and Health Sciences).Punkty Ministerialne z 2019 - aktualny rok 40 punktów. Załącznik do komunikatu Ministra Edukacji i Nauki z dnia 21 grudnia 2021 r. Lp. 32343. Posiada Unikatowy Identyfikator Czasopisma: 201159.Przypisane dyscypliny naukowe: Nauki o kulturze fizycznej (Dziedzina nauk medycznych i nauk o zdrowiu); Nauki o zdrowiu (Dziedzina nauk medycznych i nauk o zdrowiu).© The Authors 2022;This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, PolandOpen Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium,provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike.(http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited.The authors declare that there is no conflict of interests regarding the publication of this paper.Received: 07.08.2022. Revised: 10.08.2022. Accepted: 28.08.2022.Effect of glucagon-like peptide-1 (GLP-1) agonists on the example ofsemaglutide on the cardiovascular system and their role in the treatment ofobesityKamil Pondel, Kinga Kawałko, Krzysztof Bielewicz, Anna Chmura, Anna KaraśKamil Pondel, pondelkml@gmail.com, Faculty of Medicine, University of Rzeszow, PigoniaStreet 6, 35-310 Rzeszow, PolandKinga Kawałko, kingakawalko@gmail.com, Faculty of Medicine, University of Rzeszow,Pigonia Street 6, 35-310 Rzeszow, PolandKrzysztof Bielewicz, krzysztofbielewicz1@wp.pl, Faculty of Medicine, University ofRzeszow, Pigonia Street 6, 35-310 Rzeszow, PolandAnna Chmura, chmura.anna96@gmail.com, Faculty of Medicine, University of Rzeszow,Pigonia Street 6, 35-310 Rzeszow, PolandAnna Karaś, annamariakaras12@gmail.com, Faculty of Medicine, University of Rzeszow,Pigonia Street 6, 35-310 Rzeszow, PolandAbstract.Obesity nowadays affects an increasing number of people. We can talk about it when thepatient's BMI is ≥ 30.0 kg/m² (BMI 25.0-29.9 kg/m² - overweight). While obesity in itselfmay not be a problem for people suffering from it, its complications can be global andsometimes pose a serious threat to health or even life. Its main complications in thecardiovascular system include: hypercholesterolaemia, arterial hypertension, left ventricularhypertrophy, early atherosclerotic changes, heart and cerebral infarction. Treatment of obesityis based mainly on changing the patient's lifestyle - diet and physical activity, which cansometimes be problematic and difficult to apply.However, there is a new group of hypoglycaemic drugs - glucagon-like peptide-1 (GLP-1)agonists, which can make obesity treatment easier. These drugs use the incretin effect in thebody to increase insulin secretion in response to a meal containing carbohydrates and preventpostprandial hyperglycemia. In this article, we will analyze the latest studies on the effects ofGLP-1 receptor agonists, using semaglutide as an example, on the cardiovascular system andon weight loss in patients.56Key words: obesity, weight loss, GLP-1 agonists, cardiovascular riskIntroduction and purpose.Cardiovascular risk is an estimate of the likelihood of a patient developing cardiovascularcomplications such as a stroke or heart attack over the next 10 years. In Poland, currently thebest tool to assess this risk in adults is the SCORE (Systematic Coronary Risk Evaluation)scale. It allows the estimation of the 10-year risk of a fatal cardiovascular event, taking intoaccount factors such as gender, age, systolic blood pressure, total cholesterol in the blood andnicotinism [12]. The coexistence of diabetes and obesity has a significant impact on thecardiovascular system. Diabetes mellitus is a disease that accelerates the formation ofatherosclerotic processes - it intensifies inflammatory processes that have a significant impacton the growth of atherosclerotic plaque. These, in turn, narrow the diameter of the coronaryvessels, which hinders blood flow and the supply of nutrients necessary for the properfunctioning of the heart muscle, leading to the development of ischemic heart disease.According to the World Health Organization (WHO), about 1.9 billion people suffer fromexcess kilograms. About 650 million people are affected by the problem of obesity (BMI ≥30.0 kg / m²) (data for 2016). [1] We can often hear that obesity is taking epidemicproportions. This is because nowadays obesity affects increasingly younger people. In the past,obesity mainly concerned adults, but nowadays it is also more common in children. Less andless movement, more and more time spent at the computer or smartphone, and dietarymistakes, most often resulting from rush, comfort or modern trends, have a huge impact onour body weight. Such bad habits learned from childhood are fixed in adulthood, and thiscauses an increase in the number of people struggling with the problem of obesity.While obesity in itself is for many (or sometimes it is not - feeders) an aesthetic problem,its complications for the body are multidirectional and serious.Early complications of obesity: Hypertension, Insulin resistance, Type 2 diabetes, Dyslipidemia, Metabolic syndrome, NAFLD (non-alcoholic fatty liverdisease), Hypertransaminasemia (mainlyALT) Follicular calculi, Glazing of the glomeruli, Obstructive sleep apnea, bronchial asthma, Diseases of the skeletal system, Emotional disturbances (low self-esteem), Early puberty, hyperandrogenism, PCOS (polycystic ovary syndrome)Complications of obesity in adulthood: Presence of cardiovascular risk factors (hypercholesterolaemia, hypertension, type 2diabetes), The occurrence of cardiovascular events, Left ventricular hypertrophy, Shortening the life expectancy. [2]57Treating obesity is difficult. It mainly consists in changing the lifestyle by the patient andusing a diet to ensure a caloric deficit. In order to achieve a long-term treatment effect, it isimportant to slowly and steadily lose weight and to stabilize it. During conservative treatment,lasting 6 months, it is recommended that the maximum weight loss be approx. 5-10% inrelation to the initial body weight. A decrease of more than 10% in 6 months may result in adefensive reaction of the body, the effect of which is a slower metabolism and a reboundeffect (the so-called yo-yo effect). In patients with a BMI> 35 kg / m², the reduction in bodyweight may be greater, up to 20%. Then the patient learns new eating and behavioral habits,which allows you to maintain the achieved body weight as long as possible. [3] [4]In the case of grade II obesity (BMI 35-39.9 kg / m²) and the presence of comorbiditiesand grade III obesity (BMI ≥40 kg / m²), surgery (bariatric surgery) may be considered.State of knowledge.GLP-1 Agonists - Semaglutide (and Liraglutide)Semaglutide and liraglutide are analogs of glucagon-like peptide-1 (GLP-1).Semaglutide is characterized by the presence of 94% sequences homologous to human GLP-1and, as its analog, selectively binds and activates it, similar to human GLP-1.Glucagon-like peptide-1 (GLP-1) is a hormone produced by the human body that has amultidirectional effect in the regulation of appetite and glucose concentration, and also has asignificant effect on the function of the cardiovascular system. Through GLP-1 receptors,which are present in the pancreas and brain, it affects the appetite and causes a decrease inblood glucose levels by stimulating insulin secretion and reducing glucagon secretion. Thereduction in blood glucose is also caused by delaying gastric emptying after eating. Inhypoglycaemia, semaglutide reduces insulin secretion without affecting glucagon secretion. Italso inhibits the desire to reach for foods high in fat. Due to the inhibition of appetite, andthus reduced caloric supply, semaglutide reduces body fat and lowers body weight.GLP-1 receptors are also present in the heart, circulatory system, kidneys and theimmune system. In clinical trials, semaglutide reduced inflammation, had a beneficial effecton plasma lipids, and also lowered systolic blood pressure. In animal studies, it inhibited thedevelopment of atherosclerosis in the process of reducing inflammation, which prevented thedevelopment of atherosclerotic plaque. [5]Ping Zhong and colleagues conducted four studies with 3,447 patients, during whichpatients were given a weekly subcutaneous injection of semaglutide and their body weightwas monitored. Taking into account the percentage and absolute weight loss, drugadministration significantly exceeded placebo. It also showed a greater effect in reducingwaist circumference and BMI compared to placebo. The use of the drug also had a significanteffect on the improvement of cardiac and metabolic risk factors related to health. [6]Glucagon-like peptide-1 (GLP-1) receptor analogs promote weight reduction in peoplewith diabetes and were originally used to control the disease. This effect sparked the interestof scientists and explored their effects at higher doses in the treatment of obesity. For peoplewith obesity, weight loss and improved glycemia aren't the only potential benefits. It has beenestablished in clinical trials that long-acting GLP-1 is cardioprotective by lowering blood58pressure and cholesterol levels. Therefore, the use of GLP-1 receptor agonists in people atincreased risk of cardiovascular events may bring significant benefits.The first drug to be approved by the FDA for the treatment of obesity was liraglutide,manufactured by Novo Nordisk under the name Saxenda. Based on the results of efficacy andsafety studies, on June 4, 2021. Semaglutide has also been approved by the FDA for long-term weight management in people with at least one obesity-related medical condition, suchas high blood pressure, diabetes, and hypercholesterolaemia. [7]In a study that compared the effects of semaglutide to liraglutide, the reduction incaloric intake compared to placebo was greater with semaglutide (35%) than with liraglutide(approximately 16%). Semaglutide also has a greater reduction in appetite, which is lessapparent with liraglutide. This may suggest various mechanisms of caloric intake regulation,however, in order to understand the wider effects of these mechanisms, further research isneeded. [8]In the pre-registration phase III trial SUSTAIN-6 (Trial to Evaluate Cardiovascularand Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes), 3,297patients with type 2 diabetes, additionally at high cardiovascular risk, were examined. Theywere randomly matched to the study group that took either 0.5 mg or 1 mg semaglutide /week. or to the placebo group. After a 2-year follow-up period, it was found that semaglutidesignificantly (by 26%) reduced the risk of cardiovascular deaths [10].Another pre-approval phase III study - PIONEER-6 (Peptide Innovation for EarlyDiabetes Treatment) in patients with type 2 diabetes at high cardiovascular risk investigatedthe effect of oral semaglutide 14 mg / day on cardiovascular events compared to placebo .After a follow-up period of 16 months, the benefits of semaglutide over placebo wereconfirmed. Semaglutide reduced the risk of cardiovascular death and all-cause death [11].The half-life of liraglutide is approximately 13 hours, so it must be used daily in orderto maintain the therapeutic dose. The half-life of semaglutide is approximately 1 week, whichmeans that its use is limited to one dose per week. This feature of semaglutide has asignificant influence on the control of drug administration by patients. Less frequent dosing ismore comfortable for the patient, which translates into an increase in the effectiveness of thetreatment - the patient does not have to remember to take the drug every day and is less likelyto miss a dose.Conclusions.Obesity - is a disease that takes the hallmarks of an epidemic, having amultidirectional impact on human health, causing not only organic but also psychologicaldisorders - lack of acceptance, lowered self-esteem, it is also so difficult to cure. It requires alot of determination, dedication and hard work to achieve any results. Until recently, therewere no effective drugs on the market to help fight obesity. Various companies advertisedpreparations, most often herbal, of unconfirmed effectiveness, which were supposed tomiraculously make the problem of excess kilos disappear. They work mainly through adiuretic or laxative effect, which allows you to notice a slight loss of body weight, but it isassociated with the loss of water from the body, but does not reduce the amount of body fat.Recently, there is a new group of hypoglycemic drugs on the market - glucagon-likepeptide-1 (GLP-1) agonists, thanks to which the treatment of obesity may be easier. They takeadvantage of the incretin effect in the body, increase insulin secretion in response to a mealcontaining carbohydrates, and prevent postprandial hyperglycemia. Additionally, they inhibitglucagon secretion by pancreatic β cells, reduce hepatic glucose production and delay gastric59emptying. In the hypothalamic mechanism, they also reduce appetite. Their primary use in thetreatment of diabetes may be extended to support the treatment of obesity. In addition,according to the research, apart from the effect on weight loss, they have a positive effect onthe cardiovascular system and metabolism. They lower blood pressure and cholesterol, reducethe risk of cardiovascular events by preventing the development of atherosclerotic plaque andinflammation.According to the researchers, a healthy, negative-calorie diet in obese people has agreater impact on weight loss than increased physical activity. [9] The reduction of appetiteby GLP-1 agonists and their effect on reducing the desire to reach for high-fat products maysignificantly contribute to maintaining a caloric deficit and effective slimming therapy.It should not be forgotten that healthy and effective weight loss is about changing yourlifestyle and previous habits. The most beneficial is a combination of a balanced diet andexercise, which allows you to achieve a caloric deficit, and at the same time increase thecondition of the body and physical fitness. The drugs in question can be used as an effectivesupplement, not as an alternative to weight loss therapy. Due to their multidirectional effecton the body's metabolism, these products should only be used under medical supervision.60References:1. Obesity and overweight, www.who.int [accessed 13.08.2022]2. Complications of obesity in children and adolescents. Aneta Gawlik, AgnieszkaZachurzok-Buczyńska, Ewa Małecka-Tendera Department of Pediatrics,Endocrinology and Pediatric Diabetology, Medical University of Silesia in Katowice3. Volkan Yumuk i inni, European Guidelines for Obesity Management in Adults,„Obesity Facts”, 8 (6), 2015, s. 402–4244. Ewa Szczepańska, Progress in obesity treatment, "Postępy Nauk Medycznych", 28January 2008 [accessed on August 13, 2022]5. Characteristics of the medicinal product – Ozempic, INN-semaglutide6. Efficacy and safety of once-weekly semaglutide in adults with overweight or obesity:a meta-analysis. Ping Zhong, Hai Zeng, Miaochun Huang, Wenbin Fu & Zhixia Chen,Endocrine volume 75, pages 718–724 (2022)7. Clinical review of subcutaneous semaglutide for obesity. Anna Phillips PharmDCandidate, Jennifer N. Clements PharmD, FCCP, FADCES, BCPS, CDCES, BCACP,BC-ADM8. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight inAdults With Overweight or Obesity Without Diabetes. The STEP 8 RandomizedClinical Trial. Domenica M. Rubino, MD; Frank L. Greenway, MD; Usman Khalid,MD, PhD9. Aaron E. Carroll, To Lose Weight, Eating Less Is Far More Important ThanExercising More, „The New York Times”, 15 June 2015, ISSN 0362-433110. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes Steven P.Marso, M.D., Stephen C. Bain, M.D., Agostino Consoli, M.D., Freddy G.Eliaschewitz, M.D., Esteban Jódar, M.D., Lawrence A. Leiter, M.D., Ildiko Lingvay,M.D., M.P.H., M.S.C.S., Julio Rosenstock, M.D., Jochen Seufert, M.D., Ph.D., MarkL. Warren, M.D., Vincent Woo, M.D., Oluf Hansen, M.Sc., et al., for the SUSTAIN-6Investigators11. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 DiabetesMansoor Husain, M.D., Andreas L. Birkenfeld, M.D., Morten Donsmark, Ph.D.,Kathleen Dungan, M.D., M.P.H., Freddy G. Eliaschewitz, M.D., Denise R. Franco,M.D., Ole K. Jeppesen, M.Sc., Ildiko Lingvay, M.D., M.P.H., M.S.C.S., OfriMosenzon, M.D., Sue D. Pedersen, M.D., Cees J. Tack, M.D., Mette Thomsen, M.D.,D.M.Sc., et al., for the PIONEER 6 Investigators12. Conroy R.M., Pyörälä K., Fitzgerald A.P. i wsp. Estimation of ten-year risk of fatalcardiovascular disease in Europe: the SCORE project. Eur. Heart J. 2003; 24: 987–1003

Effect of glucagon-like peptide-1 (GLP-1) agonists on the example of semaglutide on the cardiovascular system and their role in the treatment of obesity.

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Effect of glucagon-like peptide-1 (GLP-1) agonists on the example of semaglutide on the cardiovascular system and their role in the treatment of obesity.

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