Obezitenin Medikal Tedavisi
Özet
Fazla kilolu (VKI ≥25 kg/m2) tüm hastalara diyet ve yaşam tarzı değişikliği önerilmelidir. İlaç tedavisi, VKI ≥30 kg/m2 ve diyet ve yaşam tarzı değişikliği ile kilo verme hedeflerini karşılayamamış kişilere önerilmektedir. Ayrıca VKI 27-29,9 kg/m2 olup obeziteyle ilişkili en az bir ek komorbiditesi bulunan (tip 2 diyabetes mellitus, koroner arter hastalığı, serebrovasküler hastalık, hipertansiyon, dislipidemi, uyku apnesi vb.) kişilere de önerilmektedir. Dünya çapında medikal tedavide birinci basamak olarak GLP-1 reseptör agonistleri önerilmektedir. Ülkemizde liraglutid 3 mg obezite tedavisi için onay almıştır. Bulantı ve kusma sık görülen fakat geçici yan etkidir. Akut pankreatit ve tiroid medüller kanser öyküsü olanlarda kullanımı kontrendikedir. Orlistat, pankreatik lipazları inhibe ederek yağ sindirimini azaltır ve tedavisi sırasında gastrointestinal yan etkiler oluşabilir. Diğer ilaçların obezite tedavisinde ülkemizde ruhsatı bulunmamaktadır. GLP-1 reseptör agonisti olan semaglutid, tip 2 diyabeti olan veya olmayan obezite hastalarında FDA onayı vardır. Sempatomimetik ilaçlar (fentermin, dietilpropion, benzfetamin ve fendimetrazin) ve kombine ilaçlar (fentermin-topiramat ve bupropion-naltrekson), GLP-1 tedavisine uygun olmayan obeziteye sahip bireyler için FDA tarafından onaylanmıştır. Medikal tedavinin etkinliği ilk 3 aydan sonra değerlendirilmelidir. Obeziteli bireylerde diyabeti olmayanlarda >%5, diyabet olanlarda ise >%3 kilo kaybı varsa tedaviye devam edilmelidir. Aksi takdirde tedavi durdurulmalıdır. Liraglutid 3 yıl ve orlistat 4 yıl boyunca güvenle kullanılabilir.
Referanslar
Garvey Wt, Mechanick Jı, Brett Em, Et Al. Amerıcan Assocıatıon Of Clınıcal Endocrınologısts And Amerıcan College Of Endocrınology Comprehensıve Clınıcal Practıce Guıdelınes For Medıcal Care Of Patıents Wıth Obesıtyexecutıve Summary complete Guidelines . Endocr Pract. 2016;22(7):842-884.
Jensen MD, Ryan DH, Apovian CM, 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 [published correction appears in Circulation. 2014 Jun 24;129(25 Suppl 2):S139-40]. Circulation. 2014;129(25 Suppl 2):S102-S138.
Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014;311(1):74-86.
Bray GA, Ryan DH. Medical therapy for the patient with obesity. Circulation. 2012;125(13):1695-1703.
Yumuk V, Tsigos C, Fried M, et al. European Guidelines for Obesity Management in Adults [published correction appears in Obes Facts. 2016;9(1):64]. Obes Facts. 2015;8(6):402-424.
Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an endocrine Society clinical practice guideline [published correction appears in J Clin Endocrinol Metab. 2015 May;100(5):2135-6]. J Clin Endocrinol Metab. 2015;100(2):342-362.
Kaplan LM, Golden A, Jinnett K, et al. Perceptions of Barriers to Effective Obesity Care: Results from the National ACTION Study. Obesity (Silver Spring). 2018;26(1):61-69.
Khera R, Murad MH, Chandar AK, et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis [published correction appears in JAMA. 2016 Sep 6;316(9):995]. JAMA. 2016;315(22):2424-2434.
Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002.
Rubino DM, Greenway FL, Khalid U, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022;327(2):138-150.
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216.
Rosenbaum M, Hirsch J, Gallagher DA, Leibel RL. Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Am J Clin Nutr. 2008;88(4):906-912.
Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365(17):1597-1604.
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 [published correction appears in Diabetes Care. 2004 Mar;27(3):856]. Diabetes Care. 2004;27(1):155-161.
Le Roux CW, Astrup A, Fujioka K, 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 [published correction appears in Lancet. 2017 Apr 8;389(10077):1398]. Lancet. 2017;389(10077):1399-1409.
Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. 2012;95(2):297-308.
Siebenhofer A, Jeitler K, Horvath K, et al. Long-term effects of weight-reducing drugs in people with hypertension. Cochrane Database Syst Rev. 2016;3:CD007654. Published 2016 Mar 2. doi:10.1002/14651858.CD007654.pub4
Douketis JD, Macie C, Thabane L, Williamson DF. Systematic review of long-term weight loss studies in obese adults: clinical significance and applicability to clinical practice. Int J Obes (Lond). 2005;29(10):1153-1167.
Avenell A, Broom J, Brown TJ, et al. Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement. Health Technol Assess. 2004;8(21):iii-182.
Li Z, Maglione M, Tu W, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med. 2005;142(7):532-546.
Sjöström L, Rissanen A, Andersen T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet. 1998;352(9123):167-172.
Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial [published correction appears in JAMA 1999 Apr 7;281(13):1174]. JAMA. 1999;281(3):235-242.
Hauptman J, Lucas C, Boldrin MN, Collins H, Segal KR. Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med. 2000;9(2):160-167.
Rössner S, Sjöström L, Noack R, Meinders AE, Noseda G. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Obes Res. 2000;8(1):49-61.
Kelley DE, Bray GA, Pi-Sunyer FX, et al. Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: A 1-year randomized controlled trial [published correction appears in Diabetes Care. 2003 Mar;26(3):971.]. Diabetes Care. 2002;25(6):1033-1041.
Miles JM, Leiter L, Hollander P, et al. Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin [published correction appears in Diabetes Care. 2002 Sep;25(9):1671.]. Diabetes Care. 2002;25(7):1123-1128.
Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study. Diabetes Care. 1998;21(8):1288-1294.
Osei-Assibey G, Adi Y, Kyrou I, Kumar S, Matyka K. Pharmacotherapy for overweight/obesity in ethnic minorities and White Caucasians: a systematic review and meta-analysis. Diabetes Obes Metab. 2011;13(5):385-393.
Leblanc ES, O'Connor E, Whitlock EP, Patnode CD, Kapka T. Effectiveness of primary care-relevant treatments for obesity in adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155(7):434-447.
Yancy WS Jr, Westman EC, McDuffie JR, et al. A randomized trial of a low-carbohydrate diet vs orlistat plus a low-fat diet for weight loss [published correction appears in JAMA Intern Med. 2015 Mar;175(3):470]. Arch Intern Med. 2010;170(2):136-145.
Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev. 2004;2003(3):CD004094.
Douglas IJ, Langham J, Bhaskaran K, Brauer R, Smeeth L. Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink. BMJ. 2013;346:f1936. Published 2013 Apr 12.
Courtney AE, O'Rourke DM, Maxwell AP. Rapidly progressive renal failure associated with successful pharmacotherapy for obesity. Nephrol Dial Transplant. 2007;22(2):621-623.
Singh A, Sarkar SR, Gaber LW, Perazella MA. Acute oxalate nephropathy associated with orlistat, a gastrointestinal lipase inhibitor. Am J Kidney Dis. 2007;49(1):153-157.
Weir MA, Beyea MM, Gomes T, et al. Orlistat and acute kidney injury: an analysis of 953 patients. Arch Intern Med. 2011;171(7):703-704.
MacWalter RS, Fraser HW, Armstrong KM. Orlistat enhances warfarin effect. Ann Pharmacother. 2003;37(4):510-512.
Bansal AB, Al Khalili Y. Orlistat. In: StatPearls. Treasure Island (FL): StatPearls Publishing; December 11, 2022.
Ladenheim EE. Liraglutide and obesity: a review of the data so far. Drug Des Devel Ther. 2015;9:1867-1875.
Lin CH, Shao L, Zhang YM, et al. An evaluation of liraglutide including its efficacy and safety for the treatment of obesity. Expert Opin Pharmacother. 2020;21(3):275-285.
Drucker DJ. GLP-1 physiology informs the pharmacotherapy of obesity. Mol Metab. 2022;57:101351.
Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016;375(4):311-322.
Pi-Sunyer X, Astrup A, Fujioka K, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015;373(1):11-22.
Davies MJ, Bergenstal R, Bode B, et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial [published correction appears in JAMA. 2016 Jan 5;315(1):90]. JAMA. 2015;314(7):687-699.
Le Roux CW, Astrup A, Fujioka K, 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 [published correction appears in Lancet. 2017 Apr 8;389(10077):1398]. Lancet. 2017;389(10077):1399-1409.
Wadden TA, Hollander P, Klein S, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study [published correction appears in Int J Obes (Lond). 2013 Nov;37(11):1514] [published correction appears in Int J Obes (Lond). 2015 Jan;39(1):187]. Int J Obes (Lond). 2013;37(11):1443-1451.
Astrup A, Rössner S, Van Gaal L, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study [published correction appears in Lancet. 2010 Mar 20;375(9719):984]. Lancet. 2009;374(9701):1606-1616.
Trujillo J. Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes. J Clin Pharm Ther. 2020;45 Suppl 1(Suppl 1):43-60.
Wharton S, Kuk JL, Luszczynski M, Kamran E, Christensen RAG. Liraglutide 3.0 mg for the management of insufficient weight loss or excessive weight regain post-bariatric surgery [published correction appears in Clin Obes. 2019 Dec;9(6):e12338]. Clin Obes. 2019;9(4):e12323.
Rosenstock J, Allison D, Birkenfeld AL, et al. Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial. JAMA. 2019;321(15):1466-1480.
Davies M, Færch L, Jeppesen OK, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021;397(10278):971-984.
Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375(19):1834-1844.
Bray GA, Greenway FL. Pharmacological treatment of the overweight patient. Pharmacol Rev. 2007;59(2):151-184.
Kim GW, Lin JE, Blomain ES, Waldman SA. Antiobesity pharmacotherapy: new drugs and emerging targets. Clin Pharmacol Ther. 2014;95(1):53-66.
Kim KK, Cho HJ, Kang HC, Youn BB, Lee KR. Effects on weight reduction and safety of short-term phentermine administration in Korean obese people. Yonsei Med J. 2006;47(5):614-625.
Kang JG, Park CY, Kang JH, Park YW, Park SW. Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity. Diabetes Obes Metab. 2010;12(10):876-882.
Bray GA. Use and abuse of appetite-suppressant drugs in the treatment of obesity. Ann Intern Med. 1993;119(7 Pt 2):707-713.
McMahon FG, Fujioka K, Singh BN, et al. Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial. Arch Intern Med. 2000;160(14):2185-2191.
Caterson I, Coutinho W, Finer N, et al. Early response to sibutramine in patients not meeting current label criteria: preliminary analysis of SCOUT lead-in period [published correction appears in Obesity (Silver Spring). 2010 May;18(5):1063]. Obesity (Silver Spring). 2010;18(5):987-994.
James WP, Caterson ID, Coutinho W, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010;363(10):905-917.
Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med. 2000;343(25):1826-1832.
Gadde KM, Allison DB, Ryan DH, 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 [published correction appears in Lancet. 2011 Apr 30;377(9776):1494]. Lancet. 2011;377(9774):1341-1352.
Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20(2):330-342.
2 new drugs for weight loss [published correction appears in Med Lett Drugs Ther. 2012 Sep 17;54(1399):76]. Med Lett Drugs Ther. 2012;54(1398):69-71.
Smith SM, Meyer M, Trinkley KE. Phentermine/topiramate for the treatment of obesity. Ann Pharmacother. 2013;47(3):340-349.
Sherman MM, Ungureanu S, Rey JA. Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults. P T. 2016;41(3):164-172.
Greenway FL, Whitehouse MJ, Guttadauria M, et al. Rational design of a combination medication for the treatment of obesity. Obesity (Silver Spring). 2009;17(1):30-39.
Sharfstein JM, Psaty BM. Evaluation of the Cardiovascular Risk of Naltrexone-Bupropion: A Study Interrupted. JAMA. 2016;315(10):984-986.
Nissen SE, Wolski KE, Prcela L, 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.
Caixàs A, Albert L, Capel I, Rigla M. Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date. Drug Des Devel Ther. 2014;8:1419-1427. Published 2014 Sep 18.
Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013;21(5):935-943.
Greenway FL, Fujioka K, Plodkowski RA, 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 [published correction appears in Lancet. 2010 Aug 21;376(9741):594] [published correction appears in Lancet. 2010 Oct 23;376(9750):1392]. Lancet. 2010;376(9741):595-605.
Srivastava G, Apovian C. Future Pharmacotherapy for Obesity: New Anti-obesity Drugs on the Horizon. Curr Obes Rep. 2018;7(2):147-161.
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216.
