A comprehensive review of semaglutide in treating Type 2 diabetes and obesity

Abstract

Type 2 diabetes (T2D) and obesity are closely interlinked metabolic disorders contributing significantly to global health challenges and economic burdens. Effective treatment strategies are crucial for improving patient outcomes and reducing healthcare costs. This review was conducted by selecting published articles that evaluate therapeutic options for individuals with T2D and obesity. A bibliographic search was performed, with a focus on the effectiveness and financial viability of semaglutide compared to other antidiabetic treatments. Obesity is a major risk factor for T2D. Global healthcare costs for T2D management are expected to reach $1.05 trillion by 2045, with obesity-related complications further escalating the economic burdens. The financial impacts of obesity-related comorbidities have been extensively documented. It has been demonstrated that a 5 - 10% weight loss can improve metabolic outcomes and reduce healthcare expenditures. Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated superior efficacy in weight reduction and glycemic control compared to other treatments. This medication also significantly reduced waist circumference and cardiovascular risks while improving lipid profiles. Cost-effectiveness analyses suggest that semaglutide offers long-term financial benefits by reducing T2D-related complications and hospitalizations. The evaluations by the Health Technology Assessment on semaglutide lend credence for including this medication in the national healthcare policies due to its potential to improve public health outcomes and aid in ensuring financial sustainability in healthcare systems. Semaglutide emerges as a highly effective therapeutic option for patients with T2D and obesity, providing both clinical and economic benefits. In summary, prioritizing access to effective weight management treatments like semaglutide can mitigate obesity-related complications, enhance quality of life, and generate substantial cost savings for healthcare providers worldwide.

Keywords

Type 2 diabetes / Obesity / Semaglutide / Healthcare systems / Health technology assessment

Funding

None.

Conflict of interest

The authors declare that there are no competing interests.

References

[1] Aldawsari, M., Almadani, F.A., Almuhammadi, N., Algabsani, S., Alamro, Y., & Aldhwayan, M. (2023). The efficacy of GLP-1 analogues on appetite parameters, gastric emptying, food preference and taste among adults with obesity: Systematic review of randomized controlled trials. Diabetes, Metabolic Syndrome and Obesity, 16:575-595. https://doi.org/10.2147/DMSO.S387116

[2] Alkhatib, N.S., Almutairi, A.R., Alkhezi, O.S., Alfayez, O.M., Al Yami, M.S., & Almohammed, O.A. (2022). Economic analysis of glucagon like peptide-1 receptor agonists from the Saudi Arabia payer perspective. Saudi Pharmaceutical Journal, 30(4):433-439. https://doi.org/10.1016/j.jsps.2022.01.018

[3] Alqahtani, S.A., Al-Omar, H.A., Alshehri, A., Abanumay, A., Alabdulkarim, H., Alrumaih, A., et al. (2023). Obesity burden and impact of weight loss in Saudi Arabia: A modelling study. Advances in Therapy, 40(3):1114-1128. https://doi.org/10.1007/s12325-022-02415-8

[4] Al-Sabah, S., ElShamy, A., Jois, S., Low, K., Gras, A., & Gulnar, E.P. (2023). The economic impact of obesity in Kuwait: A micro-costing study evaluating the burden of obesity-related comorbidities. Journal of Medical Economics, 26(1):1368-1376. https://doi.org/10.1080/13696998.2023.2265721

[5] American Diabetes Association Professional Practice Committee. (2025a). 2. Diagnosis and classification of diabetes: Standards of care in diabetes-2025. Diabetes Care, 48(Suppl 1):S27-S49. https://doi.org/10.2337/dc25-S002

[6] American Diabetes Association Professional Practice Committee. (2025b). 8. Obesity and weight management for the prevention and treatment of type 2 diabetes: Standards of care in diabetes-2025. Diabetes Care, 48(Suppl 1):S167-S180. https://doi.org/10.2337/dc25-S008

[7] Anam, M., Maharjan, S., Amjad, Z., Abaza, A., Vasavada, A.M., Sadhu, A., et al. (2022). Efficacy of semaglutide in treating obesity: A systematic review of randomized controlled trials (RCTs). Cureus, 14(12):e32610. https://doi.org/10.7759/cureus.32610

[8] Angelis, A., Lange, A., & Kanavos, P. (2018). Using health technology assessment to assess the value of new medicines: Results of a systematic review and expert consultation across eight European countries. The European Journal of Health Economics, 19(1):123-152. https://doi.org/10.1007/s10198-017-0871-0

[9] Benney, T., & Cohen, B. (2022). The international currency system revisited. Review of Keynesian Economics, 10(4):443-461.

[10] Chantzaras, A.E., & Yfantopoulos, J.N. (2018). Financial protection of households against health shocks in Greece during the economic crisis. Social Science and Medicine, 211:338-351. https://doi.org/10.1016/j.socscimed.2018.06.024

[11] Choi, J.G., Winn, A.N., Skandari, M.R., Franco, M.I., Staab, E.M., Alexander, J., et al. (2022). First-line therapy for type 2 diabetes with sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: A cost-effectiveness study. Annals of Internal Medicine, 175(10):1392-1400. https://doi.org/10.7326/M21-2941

[12] Ciardullo, S., Savare, L., Rea, F., Perseghin, G., & Corrao, G. (2024). Adherence to GLP1-RA and SGLT2-I affects clinical outcomes and costs in patients with type 2 diabetes. Diabetes/Metabolism Research and Reviews, 40(4):e3791. https://doi.org/10.1002/dmrr.3791

[13] D’Andrea, E., Wexler, D.J., Kim, S.C., Paik, J.M., Alt, E., & Patorno, E. (2023). Comparing effectiveness and safety of SGLT2 inhibitors vs DPP-4 inhibitors in patients with type 2 diabetes and varying baseline HbA1c levels. JAMA Internal Medicine, 183(3):242-254. https://doi.org/10.1001/jamainternmed.2022.6664

[14] De Bromhead, A., Jordan, D., Kennedy, F., & Seddon, J. (2023). Sterling’s farewell symphony: The end of the Sterling Area revisited. The Economic History Review, 76(2):415-444. https://doi.org/10.1111/ehr.13175

[15] Durden, E., Liang, M., Fowler, R., Panton, U.H., & Mocevic, E. (2019). The effect of early response to GLP-1 RA therapy on long-term adherence and persistence among type 2 diabetes patients in the United States. Journal of Managed Care and Specialty Pharmacy, 25(6):669-680. https://doi.org/10.18553/jmcp.2019.18429

[16] Evans, M., Engberg, S., Faurby, M., Fernandes, J., Hudson, P., & Polonsky, W. (2022). Adherence to and persistence with antidiabetic medications and associations with clinical and economic outcomes in people with type 2 diabetes mellitus: A systematic literature review. Diabetes, Obesity and Metabolism, 24(3):377-390. https://doi.org/10.1111/dom.14603

[17] Filippatos, T.D., Panagiotopoulou, T.V., & Elisaf, M.S. (2014). Adverse effects of GLP-1 receptor agonists. The Review of Diabetic Studies, 11(3-4):202-230. https://doi.org/10.1900/RDS.2014.11.202

[18] Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K.B., et al. (2020). Pathophysiology of type 2 diabetes mellitus. International Journal of Molecular Sciences, 21(17):6275. https://doi.org/10.3390/ijms21176275

[19] Gallwitz, B. (2019). Clinical use of DPP-4 inhibitors. Frontiers in Endocrinology (Lausanne), 10:389. https://doi.org/10.3389/fendo.2019.00389

[20] Gao, X., Hua, X., Wang, X., Xu, W., Zhang, Y., Shi, C., et al. (2022). Efficacy and safety of semaglutide on weight loss in obese or overweight patients without diabetes: A systematic review and meta-analysis of randomized controlled trials. Frontiers in Pharmacology, 13:935823. https://doi.org/10.3389/fphar.2022.935823

[21] Garcia-Casares, N., Gonzalez-Gonzalez, G., de la Cruz-Cosme, C., Garzon-Maldonado, F.J., de Rojas-Leal, C., Ariza, M.J., et al. (2023). Effects of GLP-1 receptor agonists on neurological complications of diabetes. Reviews in Endocrine and Metabolic Disorders, 24(4):655-672. https://doi.org/10.1007/s11154-023-09807-3

[22] Global Health & Population Project on Access to Care for Cardiometabolic Diseases (HPACC). (2021). Expanding access to newer medicines for people with type 2 diabetes in low-income and middle-income countries: A cost-effectiveness and price target analysis. Lancet Diabetes Endocrinology, 9(12):825-836. https://doi.org/10.1016/S2213-8587(21)00240-0

[23] Gu, Y., Sun, L., Zhang, W., Kong, T., Zhou, R., He, Y., et al. (2023). Comparative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor and 4 glucagon-like peptide-1 (GLP-1) receptor agonist drugs in non-alcoholic fatty liver disease: A GRADE-assessed systematic review and network meta-analysis of randomized controlled trials. Frontiers in Pharmacology, 14:1102792. https://doi.org/10.3389/fphar.2023.1102792

[24] Guan, R., Yang, Q., Yang, X., Du, W., Li, X., & Ma, G. (2022). Efficacy and safety of tirzepatide in patients with type 2 diabetes mellitus: A Bayesian network meta-analysis. Frontiers in Pharmacology, 13:998816. https://doi.org/10.3389/fphar.2022.998816

[25] Haddad, F., Dokmak, G., Bader, M., & Karaman, R. (2023). A comprehensive review on weight loss associated with anti-diabetic medications. Life (Basel), 13(4):1012. https://doi.org/10.3390/life13041012

[26] Hu, K., Huang, H., Li, H., Wei, Y., & Yao, C. (2023). Legume-derived bioactive peptides in type 2 diabetes: Opportunities and challenges. Nutrients, 15(5):1096. https://doi.org/10.3390/nu15051096

[27] Karagiannis, T., Bekiari, E., & Tsapas, A. (2023). Socioeconomic aspects of incretin-based therapy. Diabetologia, 66(10):1859-1868. https://doi.org/10.1007/s00125-023-05962-z

[28] Kennedy, C., Hayes, P., Salama, S., Hennessy, M., & Fogacci, F. (2023). The effect of semaglutide on blood pressure in patients without diabetes: A systematic review and meta-analysis. Journal of Clinical Medicine, 12(3):772. https://doi.org/10.3390/jcm12030772

[29] Lane, P., & Milesi-Ferretti, G.M. (2018). The External Wealth of Nations Revisited: International Financial Integration in the Aftermath of the Global Financial Crisis. IMF Economic Review. Vol. 66. Palgrave Macmillan: International Monetary Fund, p. 189-222. https://doi.org/10.1057/s41308-017-0048-y

[30] Laursen, H.V.B., Jorgensen, E.P., Vestergaard, P., & Ehlers, L.H. (2023). A systematic review of cost-effectiveness studies of newer non-insulin antidiabetic drugs: Trends in decision-analytical models for modelling of type 2 diabetes mellitus. Pharmacoeconomics, 41(11):1469-1514. https://doi.org/10.1007/s40273-023-01268-5

[31] Lee, D.S.U., & Lee, H. (2022). Adherence and persistence rates of major antidiabetic medications: A review. Diabetology and Metabolic Syndrome, 14(1):12. https://doi.org/10.1186/s13098-022-00785-1

[32] Ling, J., Chen, S., Zahry, N.R., & Kao, T.A. (2023). Economic burden of childhood overweight and obesity: A systematic review and meta-analysis. Obesity Reviews, 24(2):e13535. https://doi.org/10.1111/obr.13535

[33] Lv, L., Brady, B.L., Xie, L., Guevarra, M., & Turchin, A. (2024). Adherence and persistence among people with type 2 diabetes newly initiating oral semaglutide versus DPP-4is in a US real-world setting. Primary Care Diabetes, 18(5):511-517. https://doi.org/10.1016/j.pcd.2024.06.013

[34] Ma, H., Lin, Y.H., Dai, L.Z., Lin, C.S., Huang, Y., & Liu, S.Y. (2023). Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: A systematic review and network meta-analysis. BMJ Open, 13(3):e061807. https://doi.org/10.1136/bmjopen-2022-061807

[35] McCoy, R.G., Van Houten, H.K., Deng, Y., Mandic, P.K., Ross, J.S., Montori, V.M., et al. (2021). Comparison of diabetes medications used by adults with commercial insurance vs medicare advantage, 2016 to 2019. JAMA Network Open, 4(2):e2035792. https://doi.org/10.1001/jamanetworkopen.2020.35792

[36] Mentis, I. (2022). Impact of health indicators and socio-economic inequalities on Greek population’s health level in relation to causes. Acta Scientific Medical Sciences, 6(4):3-12.

[37] Mentis, Ι. (2021). The market of generic drugs in Southern Europe with the contribution of health technology assessment and competition. Arch Hellenic Medicine, 38:89-94.

[38] Mentis, Ι. (2022). The introduction of health technology assessment (HTA) in Greece and comparison with the European experience. Archives of Hellenic Medicine/ ArheiaEllenikesIatrikes, 39(3):313-321.

[39] Mentis, Ι. (2023). Correlation between the Greek gross domestic product and health expenditure during the financial crisis, with emphasis on reimbursement of the cost of diabetic health materials by the National Organization for Healthcare Services Provision. Archives of Hellenic Medicine, 40(2):260-269.

[40] Mishra, R., Raj, R., Elshimy, G., Zapata, I., Kannan, L., Majety, P., et al. (2023). Adverse events related to tirzepatide. Journal of the Endocrine Society, 7(4):bvad016. https://doi.org/10.1210/jendso/bvad016

[41] Morfonios, A., Kaitelidou, D., Baltopoulos, G., & Myrianthefs, P. (2013). The international practice of health technology assessment. Archives of Hellenic Medicine/ ArheiaEllenikesIatrikes, 30(1):19-34.

[42] Morton, J.I., Marquina, C., Shaw, J.E., Liew, D., Polkinghorne, K.R., Ademi, Z., et al. (2023). Projecting the incidence and costs of major cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: A cost-effectiveness analysis. Diabetologia, 66(4):642-656. https://doi.org/10.1007/s00125-022-05832-0

[43] Mossialos, E., & Le Grand, J. (Eds.). (2019). Health Care and Cost Containment in the European Union. London: Routledge.

[44] Nauck, M.A., & Dietrich, J.W. (2022). Understanding the restrictions in the prescription and use of potentially beneficial diabetes medications associated with low socio-economic status. The Lancet Regional Health, 14:100318. https://doi.org/10.1016/j.lanepe.2022.100318

[45] Ofori-Asenso, R., Ilomaki, J., Chin, K.L., Mazidi, M., Zomer, E., Bell, J.S., et al. (2019). Dynamics of switching, adherence, and persistence of dipeptidyl peptidase-4 inhibitors use: A nationwide cohort study. Diabetes Research and Clinical Practice, 158:107909. https://doi.org/10.1016/j.diabres.2019.107909

[46] Ofori-Asenso, R., Sahle, B.W., Chin, K.L., Mazidi, M., Ademi, Z., De Bruin, M.L., et al. (2021). Poor adherence and persistence to sodium glucose cotransporter 2 inhibitors in real-world settings: Evidence from a systematic review and meta-analysis. Diabetes Metabolism Research and Reviews, 37(1):e3350. https://doi.org/10.1002/dmrr.3350

[47] Ogundipe, O., Mazidi, M., Chin, K.L., Gor, D., McGovern, A., Sahle, B.W., et al. (2021). Real-world adherence, persistence, and in-class switching during use of dipeptidyl peptidase-4 inhibitors: A systematic review and meta-analysis involving 594,138 patients with type 2 diabetes. Acta Diabetologica, 58(1):39-46. https://doi.org/10.1007/s00592-020-01590-w

[48] Pantanetti, P., Cangelosi, G., Alberti, S., Di Marco, S., Michetti, G., Cerasoli, G., et al. (2024). Changes in body weight and composition, metabolic parameters, and quality of life in patients with type 2 diabetes treated with subcutaneous semaglutide in real-world clinical practice. Frontiers in Endocrinology (Lausanne), 15:1394506. https://doi.org/10.3389/fendo.2024.1394506

[49] Patel, T., Nageeta, F., Sohail, R., Butt, T.S., Ganesan, S., Madhurita, F., et al. (2023). Comparative efficacy and safety profile of once-weekly Semaglutide versus once-daily Sitagliptin as an add-on to metformin in patients with type 2 diabetes: A systematic review and meta-analysis. Annals of Medicine, 55(2):2239830. https://doi.org/10.1080/07853890.2023.2239830

[50] Pantanetti, P., Ronconi, V., Sguanci, M., Palomares, S. M., Mancin, S., Tartaglia, F. C. et al. (2024). Oral semaglutide in type 2 diabetes: Clinical-metabolic outcomes and quality of life in real-world practice. J Clin Med, 13(16):4752. https://doi:10.3390/jcm13164752

[51] Rea, F., Savare, L., Valsassina, V., Ciardullo, S., Perseghin, G., Corrao, G., et al. (2023). Adherence to antidiabetic drug therapy and reduction of fatal events in elderly frail patients. Cardiovascular Diabetology, 22(1):53. https://doi.org/10.1186/s12933-023-01786-8

[52] Savarese, G., Sharma, A., Pang, C., Wood, R., & Soleymanlou, N. (2023). Patient preferences for newer oral therapies in type 2 diabetes. International Journal of Cardiology, 371:526-532. https://doi.org/10.1016/j.ijcard.2022.09.009

[53] Seidu, S., Cos, X., Brunton, S., Harris, S.B., Jansson, S.P.O., Mata- Cases, M., et al. (2022). 2022 update to the position statement by Primary Care Diabetes Europe: A disease state approach to the pharmacological management of type 2 diabetes in primary care. Primary Care Diabetes, 16(2):223-244. https://doi.org/10.1016/j.pcd.2022.02.002

[54] Smith, I., Hardy, E., Mitchell, S., & Batson, S. (2022). Semaglutide 2.4 Mg for the management of overweight and obesity: Systematic literature review and meta-analysis. Diabetes Metabolic Syndrome and Obesity, 15:3961-3987. https://doi.org/10.2147/DMSO.S392952

[55] Solar, O., & Irwin, A. (2010). A Conceptual Framework for Action on the Social Determinants of Health. WHO Document Production Services. Switzerland: WHO.

[56] Tamhane, S., Rodriguez-Gutierrez, R., Hargraves, I., & Montori, V.M. (2015). Shared decision-making in diabetes care. Current Diabetes Reports, 15(12):112. https://doi.org/10.1007/s11892-015-0688-0

[57] Tentolouris, A., Vlachakis, P., Tzeravini, E., Eleftheriadou, I., & Tentolouris, N. (2019). SGLT2 Inhibitors: A review of their antidiabetic and cardioprotective effects. International Journal of Environmental Research and Public Health, 16(16):2965. https://doi.org/10.3390/ijerph16162965

[58] Turchetti, G., Spadoni, E., & Geisler, E. (2010). Health Technology Assessment. Available from: https://ieeexplore.ieee.org/abstract/document/5463009 [Last accessed on 2018 Apr 11].

[59] Uzoigwe, C., Liang, Y., Whitmire, S., & Paprocki, Y. (2021). Semaglutide once-weekly persistence and adherence versus other GLP-1 RAs in patients with type 2 diabetes in a US real-world setting. Diabetes Therapy, 12(5):1475-1489. https://doi.org/10.1007/s13300-021-01053-7

[60] Vosoughi, K., Atieh, J., Khanna, L., Khoshbin, K., Prokop, L.J., Davitkov, P., et al. (2021). Association of glucagon-like peptide 1 analogs and agonists administered for obesity with weight loss and adverse events: A systematic review and network meta-analysis. EClinicalMedicine, 42:101213. https://doi.org/10.1016/j.eclinm.2021.101213

[61] Weeda, E.R., Muraoka, A.K., Brock, M.D., & Cannon, J.M. (2021). Medication adherence to injectable glucagon-like peptide-1 (GLP-1) receptor agonists dosed once weekly vs once daily in patients with type 2 diabetes: A meta-analysis. International Journal of Clinical Practice, 75(9):e14060. https://doi.org/10.1111/ijcp.14060

[62] Weiss, T., Carr, R.D., Pal, S., Yang, L., Sawhney, B., Boggs, R., et al. (2020). Real-world adherence and discontinuation of glucagon-like peptide-1 receptor agonists therapy in type 2 diabetes mellitus patients in the United States. Patient Prefer Adherence, 14:2337-2345. https://doi.org/10.2147/PPA.S277676

[63] Wilson, R.B., Lathigara, D., & Kaushal, D. (2023). Systematic review and meta-analysis of the impact of bariatric surgery on future cancer risk. International Journal of Molecular Sciences, 24(7):6192. https://doi.org/10.3390/ijms24076192

[64] Wu, S., Lu, W., Chen, Z., Dai, Y., Chen, K., & Zhang, S. (2022). Association of glucagon-like peptide-1 receptor agonists with cardiac arrhythmias in patients with type 2 diabetes or obesity: A systematic review and meta-analysis of randomized controlled trials. Diabetology and Metabolic Syndrome, 14(1):195. https://doi.org/10.1186/s13098-022-00970-2

[65] Xie, Z., Li, J., Yang, S., Deng, W., & Chen, J. (2022). A health technology assessment based on Chinese guidelines: glucagon-like peptide-1 receptor agonist in the treatment of type 2 diabetes complicated with cardiovascular disease. Therapeutics and Clinical Risk Management, 18:889-900. https://doi.org/10.2147/TCRM.S375067

[66] Xie, Z., Yang, S., Deng, W., Li, J., & Chen, J. (2022). Efficacy and safety of liraglutide and semaglutide on weight loss in people with obesity or overweight: A systematic review. Clinical Epidemiology, 14:1463-1476. https://doi.org/10.2147/CLEP.S391819

[67] Yuan, X., Gao, Z., Yang, C., Duan, K., Ren, L., & Song, G. (2023). Comparing the effectiveness of long-term use of daily and weekly glucagon-like peptide-1 receptor agonists treatments in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus: A network meta-analysis. Frontiers in Endocrinology (Lausanne), 14:1170881. https://doi.org/10.3389/fendo.2023.1170881

[68] Zhang, Z., Zhang, Q., Tan, Y., Chen, Y., Zhou, X., Liu, S., et al. (2023). GLP-1RAs caused gastrointestinal adverse reactions of drug withdrawal: A system review and network meta-analysis. Frontiers in Endocrinology (Lausanne), 14:1149328. https://doi.org/10.3389/fendo.2023.1149328

[69] Zhu, J., Zhou, Y., Li, Q., & Wang, G. (2023). Cost-effectiveness of newer antidiabetic drugs as second-line treatment for type 2 diabetes: A systematic review. Advances in Therapy, 40(10):4216-4235. https://doi.org/10.1007/s12325-023-02612-z

[70] World Obesity Federation. Obesity: Missing the 2025 global targets. Trends, Costs and CountryReports. (2020). Available from: https://s3-eu-west-1.amazonaws.com/wof-files/970_-_WOF_Missing_the_2025_Global_Targets_Report_ART.pdf [Last accessed on 2025 Mar 18].