Semaglutide in the Treatment of Diabetes and Associated Obesity
DOI:
https://doi.org/10.12775/JEHS.2024.73.51699Keywords
GLP-1 analogs, semaglutide, diabetes, obesityAbstract
Introduction and objective: Diabetes represents one of the most significant healthcare challenges of the 21st century. The disease is frequently asymptomatic, with patients often remaining undiagnosed for extended periods and failing to seek assistance from healthcare professionals. A sedentary lifestyle, excessive caloric intake, and a lack of physical activity contribute to the development of obesity, which in turn leads to carbohydrate metabolism disorders. In this study, we will examine the relationship between diabetes and obesity, and discuss the drug semaglutide, which is used to treat type 2 diabetes and also promotes weight loss.
Review methods: Review and summary of research studies available in open-source format on Google Scholar, PubMed.
Abbreviated description of the state of knowledge: Numerous clinical studies have demonstrated the efficacy of semaglutide in improving lipid profiles and promoting weight loss. This effect is believed to be mediated by the drug's ability to slow gastric emptying. It is evident that semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, exerts a beneficial effect on carbohydrate parameters and helps to delay the occurrence of complications associated with diabetes.
Summary: A review of clinical reports and conducted studies indicates that semaglutide has the potential to enhance parameters that directly or indirectly impact the quality of life of patients with diabetes. However, the utilisation of the aforementioned pharmaceutical is associated with adverse effects, which may impede patient-physician collaboration and potentially precipitate the development of new health complications in patients. One of the effects of semaglutide treatment is a reduction in appetite, which contributes to weight loss. This property of the drug makes it suitable for use in patients with excessive body weight.
References
NFZ o zdrowiu. Cukrzyca - ezdrowie.gov.pl. (n.d.). Gov.pl. Retrieved May 23, 2024, from https://ezdrowie.gov.pl/portal/home/badania-i-dane/zdrowe-dane/raporty/nfz-o-zdrowiu-cukrzyca
Zakaźne, C. R., Ciąży, Z. P. U., & We, o. K. we i. (n.d.). Proporcjonalna umieralność (% wszystkich zgonów, Trendy rozpowszechnienia cukrzycy standaryzowane we wszystkich grupach wiekowych), według wieku. Gov.Pl. Retrieved May 23, 2024, from https://archiwum.mz.gov.pl/wp-content/uploads/2016/04/krajowy-profil-cukrzycy-wykresy.pdf
https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5345a2.htm
Chao AM, Tronieri JS, Amaro A, Wadden TA. Semaglutide for the treatment of obesity. Trends Cardiovasc Med. 2023 Apr;33(3):159-166. doi: 10.1016/j.tcm.2021.12.008. Epub 2021 Dec 21. PMID: 34942372; PMCID: PMC9209591. https://doi.org/10.1016/j.tcm.2021.12.008
Wang J-Y, Wang Q-W, Yang X-Y, Yang W, Li D-R, Jin J-Y, Zhang H-C and Zhang X-F (2023) GLP−1 receptor agonists for the treatment of obesity: Role as a promising approach. Front. Endocrinol. 14:1085799. doi: 10.3389/fendo.2023.1085799
Pandey, S.; Mangmool, S.; Parichatikanond, W. Multifaceted Roles of GLP-1 and Its Analogs: A Review on Molecular Mechanisms with a Cardiotherapeutic Perspective. Pharmaceuticals 2023, 16, 836. https://doi.org/10.3390/ph16060836
Yao H, Zhang A, Li D, Wu Y, Wang C, Wan J et al. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis BMJ 2024; 384 :e076410 doi:10.1136/bmj-2023-076410
Arastu N, Cummins O, Uribe W, et al.: Efficacy of subcutaneous semaglutide compared to placebo for weight loss in obese, non-diabetic adults: a systematic review & meta-analysis. Int J Clin Pharm, 2022
Christou GA, Katsiki N, Blundell J, et al.: Semaglutide as a promising antiobesity drug. Obes Rev, 2019;20(6):805-815
Sorli, C., Harashima, S.-I., Tsoukas, G. M., Unger, J., Karsbøl, J. D., Hansen, T., & Bain, S. C. (2017). Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. The Lancet. Diabetes & Endocrinology, 5(4), 251–260. https://doi.org/10.1016/s2213-8587(17)30013-x
Ahrén, B., Masmiquel, L., Kumar, H., Sargin, M., Karsbøl, J. D., Jacobsen, S. H., & Chow, F. (2017). Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. The Lancet. Diabetes & Endocrinology, 5(5), 341–354. https://doi.org/10.1016/s2213-8587(17)30092-x
Ahmann, A. J., Capehorn, M., Charpentier, G., Dotta, F., Henkel, E., Lingvay, I., Holst, A. G., Annett, M. P., & Aroda, V. R. (2018). Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): A 56-week, open-label, randomized clinical trial. Diabetes Care, 41(2), 258–266. https://doi.org/10.2337/dc17-0417
Aroda, V. R., Bain, S. C., Cariou, B., Piletič, M., Rose, L., Axelsen, M., Rowe, E., & DeVries, J. H. (2017). Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. The Lancet. Diabetes & Endocrinology, 5(5), 355–366. https://doi.org/10.1016/s2213-8587(17)30085-2
Rodbard, H. W., Lingvay, I., Reed, J., de la Rosa, R., Rose, L., Sugimoto, D., Araki, E., Chu, P.-L., Wijayasinghe, N., & Norwood, P. (2018). Semaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): A randomized, controlled trial. The Journal of Clinical Endocrinology and Metabolism, 103(6), 2291–2301. https://doi.org/10.1210/jc.2018-00070
Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M. L., Woo, V., Hansen, O., Holst, A. G., Pettersson, J., & Vilsbøll, T. (2016). Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. The New England Journal of Medicine, 375(19), 1834–1844. https://doi.org/10.1056/nejmoa1607141
Pratley, R. E., Aroda, V. R., Lingvay, I., Lüdemann, J., Andreassen, C., Navarria, A., & Viljoen, A. (2018). Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. The Lancet. Diabetes & Endocrinology, 6(4), 275–286. https://doi.org/10.1016/s2213-8587(18)30024-x
Lingvay, I., Catarig, A.-M., Frias, J. P., Kumar, H., Lausvig, N. L., le Roux, C. W., Thielke, D., Viljoen, A., & McCrimmon, R. J. (2019). Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trial. The Lancet. Diabetes & Endocrinology, 7(11), 834–844. https://doi.org/10.1016/s2213-8587(19)30311-0
Capehorn, M. S., Catarig, A.-M., Furberg, J. K., Janez, A., Price, H. C., Tadayon, S., Vergès, B., & Marre, M. (2020). Efficacy and safety of once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg as add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10). Diabetes & Metabolism, 46(2), 100–109. https://doi.org/10.1016/j.diabet.2019.101117
Aroda VR, Rosenstock J, Terauchi Y, Altuntas Y, Lalic NM, Morales Villegas EC, Jeppesen OK, Christiansen E, Hertz CL, Haluzík M; PIONEER 1 Investigators. PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes. Diabetes Care. 2019 Sep;42(9):1724-1732. doi: 10.2337/dc19-0749. Epub 2019 Jun 11. PMID: 31186300.
Helena W. Rodbard, Julio Rosenstock, Luis H. Canani, Chaicharn Deerochanawong, Janusz Gumprecht, Søren Østergaard Lindberg, Ildiko Lingvay, Anette Luther Søndergaard, Marianne Bach Treppendahl, Eduard Montanya, PIONEER 2 Investigators; Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial. Diabetes Care 1 December 2019; 42 (12): 2272–2281. https://doi.org/10.2337/dc19-0883
Rosenstock J, Allison D, Birkenfeld AL, Blicher TM, Deenadayalan S, Jacobsen JB, Serusclat P, Violante R, Watada H, Davies M; PIONEER 3 Investigators. 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 Apr 16;321(15):1466-1480. doi:10.1001/jama.2019.2942
Pratley R, Amod A, Tetens S, et al., on behalf of the PIONEER 4 Investigators. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet 2019;394:39-50. https://doi.org/10.1016/S0140-6736(19)31271-1
Mosenzon O, Blicher TM, Rosenlund S, Eriksson JW, Heller S, Hels OH, Pratley R, Sathyapalan T, Desouza C; PIONEER 5 Investigators. Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019 Jul;7(7):515-527. https://doi.org/10.1016/S2213-8587(19)30192-5
Zinman B, Aroda VR, Buse JB, Cariou B, Harris SB, Hoff ST, Pedersen KB, Tarp-Johansen MJ, Araki E; PIONEER 8 Investigators. Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. Diabetes Care. 2019 Dec;42(12):2262-2271. https://doi.org/10.2337/dc19-0898
Yabe D, Nakamura J, Kaneto H, Deenadayalan S, Navarria A, Gislum M, Inagaki N; PIONEER 10 Investigators. Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2020 May;8(5):392-406. https://doi.org/10.1016/S2213-8587(20)30074-7
Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., & Kushner, R. F. (2021). Once-weekly semaglutide in adults with overweight or obesity. The New England Journal of Medicine, 384(11), 989–1002. https://doi.org/10.1056/nejmoa2032183
Davies, M., Færch, L., Jeppesen, O. K., Pakseresht, A., Pedersen, S. D., Perreault, L., Rosenstock, J., Shimomura, I., Viljoen, A., Wadden, T. A., & Lingvay, I. (2021). 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, 397(10278), 971–984. https://doi.org/10.1016/s0140-6736(21)00213-0
Rubino, D., Abrahamsson, N., Davies, M., Hesse, D., Greenway, F. L., Jensen, C., Lingvay, I., Mosenzon, O., Rosenstock, J., Rubio, M. A., Rudofsky, G., Tadayon, S., Wadden, T. A., Dicker, D., Friberg, M., Sjödin, A., Dicker, D., Segal, G., Mosenzon, O., … STEP 4 Investigators. (2021). 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: The Journal of the American Medical Association, 325(14), 1414. https://doi.org/10.1001/jama.2021.3224
Garvey, W. T., Batterham, R. L., Bhatta, M., Buscemi, S., Christensen, L. N., Frias, J. P., Jódar, E., Kandler, K., Rigas, G., Wadden, T. A., Wharton, S., & the STEP 5 Study Group. (2022). Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine, 28(10), 2083–2091. https://doi.org/10.1038/s41591-022-02026-4
Kadowaki, T., Isendahl, J., Khalid, U., Lee, S. Y., Nishida, T., Ogawa, W., Tobe, K., Yamauchi, T., & Lim, S. (2022). Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial. The Lancet. Diabetes & Endocrinology, 10(3), 193–206. https://doi.org/10.1016/s2213-8587(22)00008-0
Sorli C, Harashima S, Tsoukas GM, Unger J, Karsbøl JD, Hansen T, et al. Efficacy and Safety of Once-Weekly Semaglutide Monotherapy Versus Placebo in Patients With Type 2 Diabetes (SUSTAIN 1): A Double-Blind, Randomised, Placebo-Controlled, Parallel-Group, Multinational, Multicentre Phase 3a Trial. Lancet Diabetes Endocrinol (2017) 5:251–60. doi: 10.1016/S2213-8587(17)30013-X
Smits MM, Van Raalte DH.: Safety of Semaglutide. Front Endocrinol (Lausanne), 2021;12:645563.
Wharton S, Calanna S, Davies M, Dicker D, Goldman B, Lingvay I, Mosenzon O, Rubino DM, Thomsen M, Wadden TA, Pedersen SD. Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Diabetes Obes Metab. 2022 Jan;24(1):94-105. doi: 10.1111/dom.14551. Epub 2021 Oct 4. PMID: 34514682; PMCID: PMC9293236.
Shomali M. Optimizing the Care of Patients With Type 2 Diabetes Using Incretin-Based Therapy: Focus on GLP-1 Receptor Agonists. Clin Diabetes. 2014 Jan;32(1):32-43. doi: 10.2337/diaclin.32.1.32. PMID: 26246677; PMCID: PMC4521427.
Rodbard HW, Lingvay I, Reed J, de la Rosa R, Rose L, Sugimoto D, et al. Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Tria. J Clin Endocrinol Metab (2018) 103:2291–301. doi: 10.1210/jc.2018-00070
Zinman B, Bhosekar V, Busch R, Holst I, Ludvik B, Thielke D, et al. Semaglutide Once Weekly as Add-on to SGLT-2 Inhibitor Therapy in Type 2 Diabetes (SUSTAIN 9): A Randomised, Placebo-Controlled Trial. Lancet Diabetes Endocrinol (2019) 7:356–67. doi: 10.1016/S2213-8587(19)30066-X
Davies M, Pieber TR, Hartoft-Nielsen M-L, Hansen OKH, Jabbour S, Rosenstock J. Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabete. JAMA (2017) 318:1460. doi: 10.1001/jama.2017.14752
Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, et al. Semaglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes. N Engl J Med (2016) 375:1834–44. doi: 10.1056/NEJMoa1607141
Romera I, Cebrián-Cuenca A, Álvarez-Guisasola F, Gomez-Peralta F. Reviriego J. A Review of Practical Issues on the Use of Glucagon-Like Peptide-1 Receptor Agonists for the Management of Type 2 Diabete. Diabetes Ther (2019) 10:5–19. doi: 10.1007/s13300-018-0535-9
Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC. Pancreatitis, Pancreatic, and Thyroid Cancer With Glucagon-Like Peptide-1-Based Therapies. Gastroenterology (2011) 141:150–6. doi: 10.1053/j.gastro.2011.02.018
Lando HM, Alattar M, Dua AP. Elevated Amylase and Lipase Levels in Patients Using Glucagonlike Peptide-1 Receptor Agonists or Dipeptidyl-Peptidase-4 Inhibitors in the Outpatient Setting. Endocr Pract (2012) 18:472–7. doi: 10.4158/EP11290.OR
Tokuyama H, Kawamura H, Fujimoto M, Kobayashi K, Nieda M, Okazawa T, et al. A Low-Grade Increase of Serum Pancreatic Exocrine Enzyme Levels by Dipeptidyl Peptidase-4 Inhibitor in Patients With Type 2 Diabetes. Diabetes Res Clin Pract (2013) 100:e66–9. doi: 10.1016/j.diabres.2013.03.034
Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, et al. Oral Semaglutide and Cardiovascular Outcomes in Patients With Type 2 Diabete. N Engl J Med (2019) 381:841–51. doi: 10.1056/NEJMoa1901118
Masson W, Lobo M, Barbagelata L, Lavalle-Cobo A, Nogueira JP. Acute pancreatitis due to different semaglutide regimens: An updated meta-analysis. Endocrinol Diabetes Nutr (Engl Ed). 2024 Mar;71(3):124-132. doi: 10.1016/j.endien.2024.03.012. PMID: 38555109.
Buse JB, Bode BW, Mertens A, et al. Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52- week, randomized, open-label extension of the PIONEER 7 trial. BMJ Open Diab Res Care 2020;8:e001649. doi:10.1136/ bmjdrc-2020-001649
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Copyright (c) 2024 Rafal Makuch, Alicja Chrościcka , Kamil Gała, Andrzej Czajka, Paweł Lenard, Adam Kucharski, Sara Michalska, Konrad Pilarski, Martyna Dewicka, Alicja Maria Wawrzyniak
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