Farmakoterapija gojaznosti: danas i sutra
Sažetak
Gojaznost je hronična, progresivna i recidivirajuća bolest. Prevalencija gojaznosti dostiže pandemijske razmere, baš kao i komorbiditeti povezani sa gojaznošću poput dijabetesa, kardiovaskularnih bolesti i izvesnih karcinoma. Glavni cilj lečenja gojaznosti je smanjenje rezidualnog morbiditeta. Farmakoterapija je namenjena pacijentima koji nisu odgovarajuće reagovali na izmenu životnog stila. Trenutno je šest lekova odobreno za dugoročno lečenje gojaznosti (orlistat, fentermin/topiramat, naltrekson/bupropion, liraglutid, semaglutid i tirzepatid). Većina njih, osim orlistata, pretežno deluje centralno povećanjem osećaja sitosti, kao i smanjenjem apetita i hranom izazvanog „nagrađivanja”. Najveću efikasnost u redukciji povišene telesne mase (preko 10%) ostvaruju semaglutid i tirzepatid. Iako su svi lekovi za lečenje gojaznosti pokazali povoljan uticaj na kardiometaboličke faktore rizika, samo je za liraglutid i semaglutid pokazano da smanjuju rizik od velikih kardiovaskularnih događaja kod pacijenata sa ili bez potvrđene kardiovaskularne bolesti. Personalizovani pristup, koji uzima u obzir karakteristike leka (efikasnost u smanjenju telesne mase i bezbednost leka) i karakteristike pacijenta (komorbiditeti, starost i preferencije), garantuje najbolje rezultate. U ovom radu ćemo se kritički osvrnuti na efikasnost i bezbednost trenutno odobrenih lekova za lečenje gojaznosti i onih koji su u finalnoj fazi kliničkog ispitivanja.
Reference
Chakhtoura M, Haber R, Ghezzawi M, Rhayem C, Tcheroyan R, Mantzoros CS. Pharmacotherapy of obesity: an update on the available medications and drugs under investigation. EClinicalMedicine. 2023;58:101882.
Jin X, Qiu T, Li L, Yu R, Chen X, Li C, et al. Pathophysiology of obesity and its associated diseases. Acta Pharm Sin B. 2023;13(6):2403-24.
Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403.
le Roux CW, Astrup A, Fujioka K, Greenway F, Lau DCW, Van Gaal L, et al. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet. 2017;389:1399–409.
Davies MJ, Bergenstal R, Bode B, Kushner RF, Lewin A, Skjøth TV, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. JAMA. 2015;314:687–99.
Obesity and overweight [Internet]. World Health Organization [cited 2024 Apr 12]. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15(5):288-298.
Cooper AJ, Gupta SR, Moustafa AF, Chao AM. Sex/Gender Differences in Obesity Prevalence, Comorbidities, and Treatment. Curr Obes Rep. 2021 Dec;10(4):458-466.
Burki T. European Commission classifies obesity as a chronic disease. Lancet Diabetes Endocrinol. 2021;9(7):418.
Caterson ID, Alfadda AA, Auerbach P, Coutinho W, Cuevas A, Dicker D, et al. Gaps to bridge: Misalignment between perception, reality and actions in obesity. Diabetes Obes Metab. 2019;21(8):1914-24.
Bray MS, Loos RJ, McCaffery JM, Ling C, Franks PW, Weinstock GM, et al. NIH working group report-using genomic information to guide weight management: From universal to precision treatment. Obesity (Silver Spring). 2016;24(1):14-22.
Katzmarzyk PT, Perusse L, Rice T, Gagnon J, Skinner JS, Wilmore JH, et al. Familial resemblance for coronary heart disease risk: the HERITAGE Family Study. Ethn Dis. 2000;10(2):138-47.
Czene K, Lichtenstein P, Hemminki K. Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database. Int J Cancer. 2002;99(2):260-6.
Müller TD, Blüher M, Tschöp MH, DiMarchi RD. Anti-obesity drug discovery: advances and challenges. Nat Rev Drug Discov. 2022;21(3):201-23.
Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014;129(25 Suppl 2):S102-38.
van der Klaauw AA. Neuropeptides in Obesity and Metabolic Disease. Clin Chem. 2018;64(1):173-182.
Suzuki K, Jayasena CN, Bloom SR. Obesity and appetite control. Exp Diabetes Res. 2012;2012:824305.
Busetto L, Bettini S, Makaronidis J, Roberts CA, Halford JCG, Batterham RL. Mechanisms of weight regain. Eur J Intern Med. 2021;93:3-7.
ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. 8. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S128-S139.
EMA Clinical evaluation of medicinal products used in weight control - Scientific guideline (2017) [Internet]. [cited 2024 Apr 12]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-evaluation-medicinal-products-used-weight-management-revision-1_en.pdf
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) [Internet]. Guidance for Industry Developing Products for Weight Management revision 1; 2018 [cited 2024 Apr 12]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/developing-products-weight-management-revision-1.
Verhaegen AA, Van Gaal LF. Drugs Affecting Body Weight, Body Fat Distribution, and Metabolic Function-Mechanisms and Possible Therapeutic or Preventive Measures: an Update. Curr Obes Rep. 2021;10(1):1-13.
Webb VL, Wadden TA. Intensive Lifestyle Intervention for Obesity: Principles, Practices, and Results. Gastroenterology. 2017;152(7):1752-64.
Mann T, Tomiyama AJ, Westling E, Lew AM, Samuels B, Chatman J. Medicare's search for effective obesity treatments: diets are not the answer. Am Psychol. 2007;62(3):220-33.
Fujioka K, O'Neil PM, Davies M, Greenway F, C W Lau D, Claudius B, et al. Early Weight Loss with Liraglutide 3.0 mg Predicts 1-Year Weight Loss and is Associated with Improvements in Clinical Markers. Obesity (Silver Spring). 2016;24(11):2278-88.
Electronic Medicines Compendium (eMC) [Internet]. Datapharm Ltd; c2024 [cited 2024 Apr 12]. Available from: https://www.medicines.org.uk/emc/.
Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014;311(1):74-86.
Finer N, James WP, Kopelman PG, Lean ME, Williams G. One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Int J Obes Relat Metab Disord. 2000;24(3):306-13.
Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27(1):155-61.
Patel DK, Stanford FC. Safety and tolerability of new-generation anti-obesity medications: a narrative review. Postgrad Med. 2018;130(2):173-82.
Cosentino G, Conrad AO, Uwaifo GI. Phentermine and topiramate for the management of obesity: a review. Drug Des Devel Ther. 2011;7:267-78.
Wajid I, Vega A, Thornhill K, Jenkins J, Merriman C, Chandler D, et al. Topiramate (Topamax): Evolving Role in Weight Reduction Management: A Narrative Review. Life (Basel). 2023;13(9):1845.
Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341-52.
Aronne LJ, Wadden TA, Peterson C, Winslow D, Odeh S, Gadde KM. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity (Silver Spring). 2013;21(11):2163-71.
Garvey WT, Ryan DH, Henry R, Bohannon NJ, Toplak H, Schwiers M, et al. Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome treated with phentermine and topiramate extended release. Diabetes Care. 2014;37(4):912-21.
Nourredine M, Jurek L, Angerville B, Longuet Y, de Ternay J, Derveaux A, et al. Use of Topiramate in the Spectrum of Addictive and Eating Disorders: A Systematic Review Comparing Treatment Schemes, Efficacy, and Safety Features. CNS Drugs. 2021;35(2):177-213.
Bialer M, Doose DR, Murthy B, Curtin C, Wang SS, Twyman RE, Schwabe S. Pharmacokinetic interactions of topiramate. Clin Pharmacokinet. 2004;43(12):763-80.
Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376(9741):595-605.
Grilo CM, Lydecker JA, Fineberg SK, Moreno JO, Ivezaj V, Gueorguieva R. Naltrexone-Bupropion and Behavior Therapy, Alone and Combined, for Binge-Eating Disorder: Randomized Double-Blind Placebo-Controlled Trial. Am J Psychiatry. 2022;179(12):927-37.
Nissen SE, Wolski KE, Prcela L, Wadden T, Buse JB, Bakris G, et al. Effect of Naltrexone-Bupropion on Major Adverse Cardiovascular Events in Overweight and Obese Patients With Cardiovascular Risk Factors: A Randomized Clinical Trial. JAMA. 2016;315(10):990-1004.
Pi-Sunyer X, Apovian CM, McElroy SL, Dunayevich E, Acevedo LM, Greenway FL. Psychiatric adverse events and effects on mood with prolonged-release naltrexone/bupropion combination therapy: a pooled analysis. Int J Obes (Lond). 2019;43(10):2085-94.
van Can J, Sloth B, Jensen CB, Flint A, Blaak EE, Saris WH. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes (Lond). 2014;38(6):784-93.
Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015;373(1):11-22.
Verma S, Poulter NR, Bhatt DL, Bain SC, Buse JB, Leiter LA, et al. Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke. Circulation. 2018;138(25):2884-94.
Espinosa De Ycaza AE, Brito JP, McCoy RG, Shao H, Singh Ospina N. Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review. Thyroid. 2024;34(4):403-18.
Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002.
Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-32.
Capone F, Nambiar N, Schiattarella GG. Beyond Weight Loss: the Emerging Role of Incretin-Based Treatments in Cardiometabolic HFpEF. Curr Opin Cardiol. 2024;39(3):148-53.
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-16.
Sardar MB, Nadeem ZA, Babar M. Tirzepatide: A novel cardiovascular protective agent in type 2 diabetes mellitus and obesity. Curr Probl Cardiol. 2024;49(5):102489.
Wang W, Volkow ND, Berger NA, Davis PB, Kaelber DC, Xu R. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Nat Med. 2024;30(1):168-76.
Guirguis A, Chiappini S, Papanti P GD, Vickers-Smith R, Harris D, Corkery JM, et al. Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis. Eur Neuropsychopharmacol. 2024;82:82-91.
Chen X, Zhao P, Wang W, Guo L, Pan Q. The Antidepressant Effects of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis. Am J Geriatr Psychiatry. 2024;32(1):117-27.
Melson E, Ashraf U, Papamargaritis D, Davies MJ. What is the pipeline for future medications for obesity? Int J Obes (Lond). 2024. doi: 10.1038/s41366-024-01473-y.
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