Tirzepatide – a new hope for type 2 diabetes mellitus and obesity management. A literature review.
DOI:
https://doi.org/10.12775/JEHS.2024.71.55971Keywords
tirzepatide, obesity, type 2 diabetes, weight reduction, GIP, GLP-1Abstract
INTRODUCTION AND PURPOSE. While obesity and type 2 diabetes mellitus (T2DM) are defined (according to WHO) as civilization diseases we are still searching for the ideal tool to fight them. Recently, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved tirzepatide subcutaneous injections as monotherapy or combination therapy, with diet and physical exercise, to achieve better glycemic blood levels in patients with diabetes and weight reduction among obese and overweighted patients. This review evaluates the efficacy and safety of using tirzepatide based on GIP/GLP-1 agonists clinical trials.
MATERAILS AND METHODS. Literature available in the PubMeb Database and Google Scholar Databases was reviewed using keywords.
RESULTS AND CONCLUSIONS. Tirzepatide is a novel medicine which stands against type 2 diabetes and obesity pandemic. Combining two agonists of GIP and GLP-1 receptors helps decrease glycemic blood levels, HbA1c levels and reducing body weight in more efficient way than the GLP-1 receptor agonists. All these effects have also resulted in minimizing cardiovascular risk which is observed as an improvement in heart failure, hyperlipidemia and hypertension. Beyond that, the recent data present possible positive long-term effect of tirzepatide in such diseases as MAFLD (metabolic associated fatty liver disease) and OSA (obstructive sleep apnea). However, triagonists, achieving a concurrent activation of GLP-1, GIP, and glucagon receptors, normalize body weight in a manner superior to that of monoagonists and dual agonists. Therefore, the triple agonism or other than GIP/GLP-1 combinations could soon represent a new standard for pharmaceutical interventions.
KEYWORDS: tirzepatide; obesity; type 2 diabetes; weight reduction; GIP; GLP-1.
References
I. Forzano, F. Varzideh, R. Avvisato, S. S. Jankauskas, P. Mone, G. Santulli; Tirzepatide: A Systematic Update, Int. J. Mol. Sci. 2022, 23(23), 14631; PMID: 36498958, PMCID: PMC9741068, DOI: 10.3390/ijms232314631
J. P. Frías, M. J. Davies, J. Rosenstock, F. C. Pérez Manghi, L. Fernández Landó, B. K. Bergman, B. Liu, X. Cui, K. Brown; Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes, N. Engl. J. Med. 2021 Aug, 5;385(6):503-515; PMID: 34170647, DOI: 10.1056/NEJMoa2107519
R. Sinha, D. Papamargaritis, J. A. Sargeant, M. J. Davies; Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management, J. Obes. Metab. Syndr. 2023 Mar 30; 32(1):25-45; PMID: 36750526, PMCID: PMC10088547, DOI: 10.7570/jomes22067
N. Javeed, A. V. Matveyenko; Circadian Etiology of Type 2 Diabetes Mellitus, Physiology (Bethesda) 2018 Mar 1; 33(2):138-150; PMID: 29412061, PMCID: PMC5899235, DOI: 10.1152/physiol.00003.2018
M. E. Piché, A. Tchernof, J. P. Després; Obesity Phenotypes, Diabetes, and Cardiovascular Diseases, Circ. Res. 2020 May 22; 126(11):1477-1500; PMID: 32437302, DOI: 10.1161/CIRCRESAHA.120.316101
T. Min, S. Bain; The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials, Diabetes Ther. 2021 Jan; 12(1):143-157; PMID: 33325008, PMCID: PMC7843845, DOI: 10.1007/s13300-020-00981-0
J. Rosenstock, L. Vázquez, S. Del Prato, D. Reis Franco, G. Weerakkody, B. Dai, L. Fernández Landó, B. K. Bergman, A. Rodríguez; Achieving Normoglycemia With Tirzepatide: Analysis of SURPASS 1-4 Trials, Diabetes Care 2023 Nov 1; 46(11):1986-1992; PMID: 37673061, PMCID: PMC10620542, DOI: 10.2337/dc23-0872
S. D. Pedersen, F. Giorgino, G. Umpierrez, V. T. Thieu, A. Rodríguez, C. Nicolay, L. Fernández Landó, C. A. Karanikas, J. Kiljanski; Relationship between body weight change and glycaemic control with tirzepatide treatment in people with type 2 diabetes: A post hoc assessment of the SURPASS clinical trial programme, Diabetes Obes. Metab. 2023 Sep; 25(9):2553-2560; PMID: 37246796, DOI: 10.1111/dom.15140
A. M. Jastreboff, L. J. Aronne, N. N. Ahmad, S. Wharton, L. Connery, B. Alves, A. Kiyosue, S. Zhang, B. Liu, M. C. Bunck, A. Stefanski; Tirzepatide Once Weekly for the Treatment of Obesity, N. Engl. J. Med. 2022 Jul 21; 387(3):205-216; PMID: 35658024, DOI: 10.1056/NEJMoa2206038
D. Dahl, Y. Onishi, P. Norwood, R. Huh, R. Bray, H. Patel, Á. Rodríguez; Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial, JAMA 2022 Feb 8; 327(6):534-545; PMID: 35133415, PMCID: PMC8826179, DOI: 10.1001/jama.2022.0078
M. A. Nauck, D. A. D'Alessio; Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction, Cardiovasc. Diabetol. 2022 Sep 1; 21(1):169; PMID: 36050763, PMCID: PMC9438179, DOI: 10.1186/s12933-022-01604-7
F. S. Willard, J. D. Douros, M. Bn Gabe, A. D. Showalter, D. B. Wainscott, T. M. Suter, M. E. Capozzi, W. Jc van der Velden, C. Stutsman, G. R. Cardona, S. Urva, P. J. Emmerson, J. J. Holst, D. A. D'Alessio, M. P. Coghlan, M. M. Rosenkilde, J. E. Campbell, K. W. Sloop; Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist, JCI Insight 2020 Sep 3; 5(17):e140532; PMID: 32730231, PMCID: PMC7526454, DOI: 10.1172/jci.insight.140532
C. W. le Roux, S. Zhang, L. J. Aronne, R. F. Kushner, A. M. Chao, S. Machineni, J. Dunn, F. B. Chigutsa, N. N. Ahmad, M. C. Bunck; Tirzepatide for the treatment of obesity: Rationale and design of the SURMOUNT clinical development program, Obesity (Silver Spring) 2023 Jan; 31(1):96-110; PMID: 36478180, PMCID: PMC10107501, DOI: 10.1002/oby.23612
S. Del Prato, S. E. Kahn, I. Pavo, G. J. Weerakkody, Z. Yang, J. Doupis, D. Aizenberg, A. G. Wynne, J. S. Riesmeyer, R. J. Heine, R. J. Wiese; Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial, Lancet 2021 Nov 13; 398(10313):1811-1824; PMID: 34672967, DOI: 10.1016/S0140-6736(21)02188-7
L. Gettman; New Drug: Tirzepatide (Mounjaro™), Sr Care Pharm 2023 Feb 1; 38(2):50-62; PMID: 36751934, DOI: 10.4140/TCP.n.2023.50
V. P. Chavda, J. Ajabiya, D. Teli, J. Bojarska, V. Apostolopoulos; Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review, Molecules 2022 Jul 5; 27(13):4315; PMID: 35807558, PMCID: PMC9268041, DOI: 10.3390/molecules27134315
N. Sattar, D. K. McGuire, I. Pavo, G. J. Weerakkody, H. Nishiyama, R. J. Wiese, S. Zoungas; Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis, Nat. Med. 2022 Mar; 28(3):591-598; PMID: 35210595, PMCID: PMC8938269, DOI: 10.1038/s41591-022-01707-4
S. L. Anderson, J. C. Marrs; Tirzepatide for type 2 diabetes, Drugs Context 2023 Aug 22: 12:2023-6-1; PMID: 37664792, PMCID: PMC10470858, DOI: 10.7573/dic.2023-6-1
A. Gastaldelli, K. Cusi, L. Fernández Landó, R. Bray, B. Brouwers, Á. Rodríguez; Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial, Lancet Diabetes Endocrinol. 2022 Jun; 10(6):393-406; PMID: 35468325, DOI: 10.1016/S2213-8587(22)00070-5
P. Dutta, Y. Kumar, A. T. Babu, S. Giri Ravindran, A. Salam, B. Rai, A. Baskar, A. Dhawan, M. Jomy; Tirzepatide: A Promising Drug for Type 2 Diabetes and Beyond, Cureus 2023 May 1; 15(5):e38379; PMID: 37265914, PMCID: PMC10231274, DOI: 10.7759/cureus.38379
Z. Krauss, A. Hintz, R. Fisk; Tirzepatide: Clinical review of the "twincretin" injectable, Am. J. Health Syst. Pharm. 2023 Jul 7; 80(14):879-888; PMID: 37070418, DOI: 10.1093/ajhp/zxad080
H. R. Karrar, M. I. Nouh, Y. I. Nouh, M. I. Nouh, A. S. K. Alhindi, Y. H. Hemeq, A. M. Aljameeli, J. A. Aljuaid, S. J. Alzahrani, A. A. Alsatami, M. A. Alkredees, A. O. Almuqati, S. N. Abanmi, A. M. Alshehri; Tirzepatide-Induced Gastrointestinal Manifestations: A Systematic Review and Meta-Analysis, Cureus 2023 Sep 27; 15(9):e46091; PMID: 37908927; PMCID: PMC10614464, DOI: 10.7759/cureus.46091
J. Andraos, H. Muhar, S. R. Smith; Beyond glycemia: Comparing tirzepatide to GLP-1 analogues, Rev. Endocr. Metab. Disord. 2023 Dec; 24(6):1089-1101; PMID: 37526853, PMCID: PMC10697893, DOI: 10.1007/s11154-023-09825-1
M. B. Sardar, Z. A. Nadeem, M. Babar; Tirzepatide: A novel cardiovascular protective agent in type 2 diabetes mellitus and obesity, Curr. Probl. Cardiol. 2024 May; 49(5):102489; PMID: 38417475, DOI: 10.1016/j.cpcardiol.2024.102489
R. Mishra, R. Raj, G. Elshimy, I. Zapata, L. Kannan, P. Majety, D. Edem, R. Correa; Adverse Events Related to Tirzepatide, J. Endocr. Soc. 2023 Jan 26; 7(4):bvad016; PMID: 36789109, PMCID: PMC9915969, DOI: 10.1210/jendso/bvad016
J. Novograd, J. A. Mullally, W. H. Frishman; Tirzepatide for Weight Loss: Can Medical Therapy "Outweigh" Bariatric Surgery?, Cardiol. Rev. 2023 Sep-Oct;31(5):278-283; PMID: 36688833, DOI: 10.1097/CRD.0000000000000515
T. Karagiannis, I. Avgerinos, A. Liakos, S. Del Prato, D. R. Matthews, A. Tsapas, E. Bekiari; Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis, Diabetologia 2022 Aug;65(8): 1251-1261; PMID: 35579691, PMCID: PMC9112245, DOI: 10.1007/s00125-022-05715-4
M. K. Thomas, A. Nikooienejad, R. Bray, X. Cui, J. Wilson, K. Duffin, Z. Milicevic, A. Haupt, D. A. Robins; Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes, J. Clin. Endocrinol. Metab. 2021 Jan 23; 106(2):388-396; PMID: 33236115, PMCID: PMC7823251, DOI: 10.1210/clinem/dgaa863
I. Lingvay, A. Yy Cheng, J. A. Levine, E. Gomez-Valderas, S. E. Allen, K. Ranta, A. Torcello-Gómez, V. T. Thieu; Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: A post hoc analysis of the SURPASS-1 to -5 studies, Diabetes Obes. Metab. 2023 Apr; 25(4):965-974; PMID: 36514843, DOI: 10.1111/dom.14943
H. Patel, K. Khunti, H. W. Rodbard, H. S. Bajaj, R. Bray, Z. Kindracki, Á. Rodríguez; Gastrointestinal adverse events and weight reduction in people with type 2 diabetes treated with tirzepatide in the SURPASS clinical trials, Diabetes Obes. Metab. 2024 Feb; 26(2):473-481; PMID: 37853960, DOI: 10.1111/dom.15333
S. J. Nicholls, S. Tofé, C. W. le Roux, D. A. D'Alessio, R. J. Wiese, I. Pavo, K. Brown, G. J. Weerakkody, M. Zeytinoglu, I. C. Romera; Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: a post hoc analysis from the SURPASS Clinical Trial Program, Cardiovasc. Diabetol. 2024 Feb 10; 23(1): 63; PMID: 38341541, PMCID: PMC10859014, DOI: 10.1186/s12933-024-02147-9
R. J. Samms, M. P. Coghlan, K. W. Sloop; How May GIP Enhance the Therapeutic Efficacy of GLP-1?, Trends Endocrinol. Metab. 2020 Jun; 31(6):410-421; PMID: 32396843, DOI: 10.1016/j.tem.2020.02.006
R. A. Lafferty, P. R. Flatt, N. Irwin; GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy, Expert Opin. Pharmacother. 2023 Apr; 24(5):587-597; PMID: 36927378, DOI: 10.1080/14656566.2023.2192865
R. Loomba, M. L. Hartman, E. J. Lawitz, R. Vuppalanchi, J. Boursier, E. Bugianesi, M. Yoneda, C. Behling, O. W. Cummings, Y. Tang, B. Brouwers, D. A. Robins, A. Nikooie, M. C. Bunck, A. Haupt, A. J. Sanyal; Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis, N. Engl. J. Med. 2024 Jul 25; 391(4):299-310; PMID: 38856224, DOI: 10.1056/NEJMoa2401943
A. Jakubowska, C. W. le Roux, A. Viljoen; The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update, Endocrinol. Metab. (Seoul) 2024 Feb; 39(1):12-22; PMID: 38356208, PMCID: PMC10901658, DOI: 10.3803/EnM.2024.1942
P. J. Knerr, S. A. Mowery, J. D. Douros, B. Premdjee, K. Rahr Hjøllund, Y. He, A. M. Kruse Hansen, A. K. Olsen, D. Perez-Tilve, R. D. DiMarchi, B. Finan; Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice, Mol. Metab. 2022 Sep: 63:101533; PMID: 35809773, PMCID: PMC9305623, DOI: 10.1016/j.molmet.2022.101533
A. Malhotra, R. R. Grunstein, I. Fietze, T. E. Weaver, S. Redline, A. Azarbarzin, S. A. Sands, R. J. Schwab, J. P. Dunn, S. Chakladar, M. C. Bunck, J. Bednarik; Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity, N. Engl. J. Med. 2024 Jun 21; PMID: 38912654, DOI: 10.1056/NEJMoa2404881
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