Tirzepatide - a novel dual GLP-1 and GIP receptor agonist used in pharmacotherapy of obesity: A literature review
DOI:
https://doi.org/10.12775/JEHS.2023.18.01.003Keywords
tirzepatide, obesity, obesity treatment, anti-obesity drug, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1Abstract
Background: Obesity is a chronic disease, which along with its complications, poses a huge threat to both our health as individuals and our healthcare as a community.
Objective: The aim of this work is to review efficacy and safety of Tirzepatide, a novel dual GIP/GLP-1 receptor agonist in the treatment of obesity
Method: A literature review was conducted on databases such as PubMed and Google Scholar using terms “obesity”, “obesity treatment”, “glucagon-like peptide 1”, “Glucose-dependent insulinotropic polypeptide”, “Tirzepatide” as keywords. The review was performed in accordance with the PRISMA guidelines.
Results: Administration of tirzepatide once weekly provides a substantial and sustained reduction in bodyweight with little side effects.
Conclusions: Clinical trials showed both high efficacy and safety of Tirzepatide in management of obesity. Due to its novel, broadened mechanism of action it seems to be the most effective drug for reducing bodyweight available on the market. Tirzepatide could be our answer to tackling the problem of world-wide obesity epidemic.
References
Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253. PMID: 11234459.
Katta N, Loethen T, Lavie CJ, Alpert MA. Obesity and Coronary Heart Disease: Epidemiology, Pathology, and Coronary Artery Imaging. Curr Probl Cardiol. 2021 Mar;46(3):100655. doi: 10.1016/j.cpcardiol.2020.100655. Epub 2020 Jul 22. PMID: 32843206.
Schnurr TM, Jakupović H, Carrasquilla GD, Ängquist L, Grarup N, Sørensen TIA, Tjønneland A, Overvad K, Pedersen O, Hansen T, Kilpeläinen TO. Obesity, unfavourable lifestyle and genetic risk of type 2 diabetes: a case-cohort study. Diabetologia. 2020 Jul;63(7):1324-1332. doi: 10.1007/s00125-020-05140-5. Epub 2020 Apr 15. PMID: 32291466.
Chrysant SG. Pathophysiology and treatment of obesity-related hypertension. J Clin Hypertens (Greenwich). 2019 May;21(5):555-559. doi: 10.1111/jch.13518. Epub 2019 Mar 24. PMID: 30907058; PMCID: PMC8030569.
Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Metabolism. 2019 Mar;92:82-97. doi: 10.1016/j.metabol.2018.11.014. Epub 2018 Nov 29. PMID: 30502373.
Selman A, Burns S, Reddy AP, Culberson J, Reddy PH. The Role of Obesity and Diabetes in Dementia. Int J Mol Sci. 2022 Aug 17;23(16):9267. doi: 10.3390/ijms23169267. PMID: 36012526; PMCID: PMC9408882.
Grzegorz Andrzej Buzuk, *Badanie związku nadwagi i otyłości z obrazem klinicznym wybranych rodzajów depresji.*, Poznań: Katedra i Klinika Endokrynologii, Przemiany Materii i Chorób Wewnętrznych Uniwersytetu Medycznego w Poznaniu, 2014.
GBD 2015 Obesity Collaborators; Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, Marczak L, Mokdad AH, Moradi-Lakeh M, Naghavi M, Salama JS, Vos T, Abate KH, Abbafati C, Ahmed MB, Al-Aly Z, Alkerwi A, Al-Raddadi R, Amare AT, Amberbir A, Amegah AK, Amini E, Amrock SM, Anjana RM, Ärnlöv J, Asayesh H, Banerjee A, Barac A, Baye E, Bennett DA, Beyene AS, Biadgilign S, Biryukov S, Bjertness E, Boneya DJ, Campos-Nonato I, Carrero JJ, Cecilio P, Cercy K, Ciobanu LG, Cornaby L, Damtew SA, Dandona L, Dandona R, Dharmaratne SD, Duncan BB, Eshrati B, Esteghamati A, Feigin VL, Fernandes JC, Fürst T, Gebrehiwot TT, Gold A, Gona PN, Goto A, Habtewold TD, Hadush KT, Hafezi-Nejad N, Hay SI, Horino M, Islami F, Kamal R, Kasaeian A, Katikireddi SV, Kengne AP, Kesavachandran CN, Khader YS, Khang YH, Khubchandani J, Kim D, Kim YJ, Kinfu Y, Kosen S, Ku T, Defo BK, Kumar GA, Larson HJ, Leinsalu M, Liang X, Lim SS, Liu P, Lopez AD, Lozano R, Majeed A, Malekzadeh R, Malta DC, Mazidi M, McAlinden C, McGarvey ST, Mengistu DT, Mensah GA, Mensink GBM, Mezgebe HB, Mirrakhimov EM, Mueller UO, Noubiap JJ, Obermeyer CM, Ogbo FA, Owolabi MO, Patton GC, Pourmalek F, Qorbani M, Rafay A, Rai RK, Ranabhat CL, Reinig N, Safiri S, Salomon JA, Sanabria JR, Santos IS, Sartorius B, Sawhney M, Schmidhuber J, Schutte AE, Schmidt MI, Sepanlou SG, Shamsizadeh M, Sheikhbahaei S, Shin MJ, Shiri R, Shiue I, Roba HS, Silva DAS, Silverberg JI, Singh JA, Stranges S, Swaminathan S, Tabarés-Seisdedos R, Tadese F, Tedla BA, Tegegne BS, Terkawi AS, Thakur JS, Tonelli M, Topor-Madry R, Tyrovolas S, Ukwaja KN, Uthman OA, Vaezghasemi M, Vasankari T, Vlassov VV, Vollset SE, Weiderpass E, Werdecker A, Wesana J, Westerman R, Yano Y, Yonemoto N, Yonga G, Zaidi Z, Zenebe ZM, Zipkin B, Murray CJL. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med. 2017 Jul 6;377(1):13-27. doi: 10.1056/NEJMoa1614362. Epub 2017 Jun 12. PMID: 28604169; PMCID: PMC5477817.
Strona internetowa World Health Organisation [https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight](https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight) (dostęp 09.02.2023).
Strona internetowa World Obesity Federation [https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2022](https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2022) (dostęp 09.02.2023).
Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet. 2011 Aug 27;378(9793):815-25. doi: 10.1016/S0140-6736(11)60814-3. Erratum in: Lancet. 2011 Nov 19;378(9805):1778. PMID: 21872750.
[https://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight](https://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight) ( dostęp 11.02.2023).
Michał Wąsowski, Magdalena Walicka, Ewa Marcinowska-Suchowierska, *Otyłość – definicja, epidemiologia, patogeneza*, „Postępy Nauk Medycznych”, XXVI (4), 2013.
Purnell JQ. Definitions, Classification, and Epidemiology of Obesity. 2018 Apr 12. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Hofland J, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): [MDText.com](http://mdtext.com/), Inc.; 2000–. PMID: 25905390.
1998 Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults--The Evidence Report. National Institutes of Health. Obes Res 6 Suppl 2:51S-209S
Foster G. The behavioral approach to treating obesity. Am Heart J. 2006 Mar;151(3):625-7. doi: 10.1016/j.ahj.2005.03.003. PMID: 16504623.
Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, Hu FB, Hubbard VS, Jakicic JM, Kushner RF, Loria CM, Millen BE, Nonas CA, Pi-Sunyer FX, Stevens J, Stevens VJ, Wadden TA, Wolfe BM, Yanovski SZ, Jordan HS, Kendall KA, Lux LJ, Mentor-Marcel R, Morgan LC, Trisolini MG, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Obesity Society. 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 Jun 24;129(25 Suppl 2):S102-38. doi: 10.1161/01.cir.0000437739.71477.ee. Epub 2013 Nov 12. Erratum in: Circulation. 2014 Jun 24;129(25 Suppl 2):S139-40. PMID: 24222017; PMCID: PMC5819889.
Bray GA, Heisel WE, Afshin A, Jensen MD, Dietz WH, Long M, Kushner RF, Daniels SR, Wadden TA, Tsai AG, Hu FB, Jakicic JM, Ryan DH, Wolfe BM, Inge TH. The Science of Obesity Management: An Endocrine Society Scientific Statement. Endocr Rev. 2018 Apr 1;39(2):79-132. doi: 10.1210/er.2017-00253. PMID: 29518206; PMCID: PMC5888222.
Korner J, Aronne LJ. The emerging science of body weight regulation and its impact on obesity treatment. J Clin Invest. 2003 Mar;111(5):565-70. doi: 10.1172/JCI17953. PMID: 12618507; PMCID: PMC151906.
Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011 Oct 27;365(17):1597-604. doi: 10.1056/NEJMoa1105816. PMID: 22029981.
Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, Nadolsky K, Pessah-Pollack R, Plodkowski R; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY. Endocr Pract. 2016 Jul;22 Suppl 3:1-203. doi: 10.4158/EP161365.GL. Epub 2016 May 24. PMID: 27219496.
Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. Mol Metab. 2021 Apr;46:101102. doi: 10.1016/j.molmet.2020.101102. Epub 2020 Oct 14. PMID: 33068776; PMCID: PMC8085572.
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 Feb;9(2):160-7. doi: 10.1001/archfami.9.2.160. PMID: 10693734.
Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, Day WW. 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 Apr 16;377(9774):1341-52. doi: 10.1016/S0140-6736(11)60205-5. Epub 2011 Apr 8. Erratum in: Lancet. 2011 Apr 30;377(9776):1494. PMID: 21481449.
Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, Kim DD, Dunayevich E; COR-I Study Group. 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 Aug 21;376(9741):595-605. doi: 10.1016/S0140-6736(10)60888-4. Epub 2010 Jul 29. Erratum in: Lancet. 2010 Aug 21;376(9741):594. Erratum in: Lancet. 2010 Oct 23;376(9750):1392. PMID: 20673995
Pressley H, Cornelio CK, Adams EN. Setmelanotide: A Novel Targeted Treatment for Monogenic Obesity. J Pharm Technol. 2022 Dec;38(6):368-373. doi: 10.1177/87551225221116010. Epub 2022 Aug 30. PMID: 36311304; PMCID: PMC9608104.
Tchang BG, Aras M, Kumar RB, Aronne LJ. Pharmacologic Treatment of Overweight and Obesity in Adults. 2021 Aug 2. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Hofland J, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): [MDText.com](http://mdtext.com/), Inc.; 2000–. PMID: 25905267.
Kim KS, Seeley RJ, Sandoval DA. Signalling from the periphery to the brain that regulates energy homeostasis. Nat Rev Neurosci. 2018 Apr;19(4):185-196. doi: 10.1038/nrn.2018.8. Epub 2018 Feb 22. PMID: 29467468; PMCID: PMC9190118.
Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. Cell Metab. 2018 Apr 3;27(4):740-756. doi: 10.1016/j.cmet.2018.03.001. PMID: 29617641. ****
Skibicka KP. The central GLP-1: implications for food and drug reward. Front Neurosci. 2013 Oct 14;7:181. doi: 10.3389/fnins.2013.00181. PMID: 24133407; PMCID: PMC3796262.
Samms RJ, Coghlan MP, Sloop KW. How May GIP Enhance the Therapeutic Efficacy of GLP-1? Trends Endocrinol Metab. 2020 Jun;31(6):410-421. doi: 10.1016/j.tem.2020.02.006. Epub 2020 Mar 16. PMID: 32396843.
Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3. PMID: 30473097; PMCID: PMC6308032.
Ryan DH, Yockey SR. Weight Loss and Improvement in Comorbidity: Differences at 5%, 10%, 15%, and Over. Curr Obes Rep. 2017 Jun;6(2):187-194. doi: 10.1007/s13679-017-0262-y. PMID: 28455679; PMCID: PMC5497590.
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4. PMID: 35658024.
Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C, Urva S, Gimeno RE, Milicevic Z, Robins D, Haupt A. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018 Nov 17;392(10160):2180-2193. doi: 10.1016/S0140-6736(18)32260-8. Epub 2018 Oct 4. PMID: 30293770.
Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25. PMID: 34170647.
Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DC, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JP; SCALE Obesity and Prediabetes NN8022-1839 Study Group. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015 Jul 2;373(1):11-22. doi: 10.1056/NEJMoa1411892. PMID: 26132939.
Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10. PMID: 33567185.
Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I; STEP 2 Study Group. 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 Mar 13;397(10278):971-984. doi: 10.1016/S0140-6736(21)00213-0. Epub 2021 Mar 2. PMID: 33667417.
Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, Lingvay I, Mosenzon O, Rosenstock J, Rubio MA, Rudofsky G, Tadayon S, Wadden TA, Dicker D; STEP 4 Investigators. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1414-1425. doi: 10.1001/jama.2021.3224. PMID: 33755728; PMCID: PMC7988425.
Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, Mao H, Cui X, Karanikas CA, Thieu VT. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021 Jul 10;398(10295):143-155. doi: 10.1016/S0140-6736(21)01324-6. Epub 2021 Jun 27. Erratum in: Lancet. 2021 Jul 17;398(10296):212. PMID: 34186022.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Bartłomiej Stachyra; Marta Wolanin, Cezary Stawikowski, Bartłomiej Zielonka, Aleksandra Osińska, Izabela Wolanin, Karolina Madej, Barbara Dengler, Ilona Kowalczyk, Paulina Krawiec
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 986
Number of citations: 0