Comparison of the role of sitagliptin and sulfonylureas in the treatment of type 2 diabetes Review article
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Published:
Nov 30, 2025
Keywords:
dipeptidyl peptidase 4 inhibitors, sitagliptin, sulphonylureas, type 2 diabetes
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Abstract
Sitagliptin and sulfonylureas in the pharmacological management of type 2 diabetes represent a group of secretagogues, that is, drugs that stimulate pancreatic β cells to secrete insulin. In current therapeutic regimens for type 2 diabetes, these agents are primarily used for therapy intensification, enhancing the hypoglycemic effect of previously introduced medications. However, they differ significantly in terms of safety profile and potency: sitagliptin, unlike sulfonylureas, does not carry a risk of hypoglycemia and does not lead to weight gain, though it provides a weaker glucose-lowering effect. Therefore, sitagliptin represents a valuable therapeutic option for overweight patients, not treated with GLP-1 receptor agonists or tirzepatide, and for those with cardiovascular disease or other comorbidities that increase susceptibility to the adverse effects of hypoglycemia.
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How to Cite
Skrzypek, M., & Fałkowska, B. (2025). Comparison of the role of sitagliptin and sulfonylureas in the treatment of type 2 diabetes. Medycyna Faktow (J EBM), 18(3(68), 405-410. https://doi.org/10.24292/01.MF.0325.11
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14. Rosenstock J, Kahn SE, Johansen OE et al.; CAROLINA Investigators. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. JAMA. 2019; 322(12): 1155-66. http://doi.org/10.1001/jama.2019.13772.
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16. Vaccaro O, Masulli M, Riccardi G. Glucose lowering strategies and cardiovascular disease in type 2 diabetes – teachings from the TOSCA.IT study. Nutr Metab Cardiovasc Dis. 2018; 28(7): 722-6. http://doi.org/10.1016/j.numecd.2018.04.008.
17. Khunti K, Chatterjee S, Gerstein HC et al. Do sulphonylureas still have a place in clinical practice? Lancet Diabetes Endocrinol. 2018; 6(10): 821-32. http://doi.org/10.1016/S2213-8587(18)30025-1.
2. Razavi M, Wei YY, Rao XQ et al. DPP-4 inhibitors and GLP-1RAs: cardiovascular safety and benefits. Mil Med Res. 2022; 9(1): 45. http://doi.org/10.1186/s40779-022-00410-2.
3. Zalecenia kliniczne dotyczące postępowania u osób z cukrzycą – 2025. Stanowisko Polskiego Towarzystwa Diabetologicznego. Curr Top Diabetes. 2025; 5(1).
4. Dzida G. Pochodne sulfonylomocznika i glinidy. In: Cukrzyca. Tom 1. Sieradzki J (ed.). Via Medica, Gdańsk 2025: 466-75.
5. Czupryniak L, Kowalska I, Małecki MT. Ogólne zasady leczenia cukrzycy typu 2. In: Cukrzyca. Tom 1. Sieradzki J (ed.). Via Medica, Gdańsk 2025: 489-91.
6. Davies MJ, Aroda VR, Collins BS et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022; 45(11): 2753-86. http://doi.org/10.2337/dci22-0034.
7. Pharmacologic approaches to glycemic treatment: standards of care in diabetes – 2025. American Diabetes Association. Diabetes Care. 2025; 48(Suppl 1): S181-206.
8. Szymańska-Garbacz E, Czupryniak L. Problemy w leczeniu cukrzycy: 93 przypadki kliniczne. Medycyna Praktyczna, Kraków 2018: 104-13.
9. Inzucchi SE, Tunceli K, Qiu Y et al. Progression to insulin therapy among patients with type 2 diabetes treated with sitagliptin or sulphonylurea plus metformin dual therapy. Diabetes Obes Metab. 2015; 17(10): 956-64. http://doi.org/10.1111/dom.12489.
10. Glycemic goals and hypoglycemia: standards of care in diabetes – 2025. American Diabetes Association. Diabetes Care. 2025; 48(Suppl 1): S128-45.
11. Starke P, Thürmann P, Grobe T et al. Real-World Harm Reduction of Metformin Plus DPP4 Inhibitors versus Metformin Plus Sulfonylureas in Older Adults: A Target Trial Emulation Using German Claims Data. Drugs Aging. 2025; 42(7): 655-63. http://doi.org/10.1007/s40266-025-01218-0.
12. Green JB, Bethel MA, Armstrong PW et al.; TECOS Study Group. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015; 373(3): 232-42. http://doi.org/10.1056/NEJMoa1501352.
13. Shih CJ, Chen HT, Kuo SC et al. Cardiovascular Outcomes of Dipeptidyl Peptidase-4 Inhibitors in Elderly Patients With Type 2 Diabetes: A Nationwide Study. J Am Med Dir Assoc. 2016; 17(1): 59-64. http://doi.org/10.1016/j.jamda.2015.10.009.
14. Rosenstock J, Kahn SE, Johansen OE et al.; CAROLINA Investigators. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. JAMA. 2019; 322(12): 1155-66. http://doi.org/10.1001/jama.2019.13772.
15. ADVANCE Collaborative Group; Patel A, MacMahon S, Chalmers J et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008; 358(24): 2560-72. http://doi.org/10.1056/NEJMoa0802987.
16. Vaccaro O, Masulli M, Riccardi G. Glucose lowering strategies and cardiovascular disease in type 2 diabetes – teachings from the TOSCA.IT study. Nutr Metab Cardiovasc Dis. 2018; 28(7): 722-6. http://doi.org/10.1016/j.numecd.2018.04.008.
17. Khunti K, Chatterjee S, Gerstein HC et al. Do sulphonylureas still have a place in clinical practice? Lancet Diabetes Endocrinol. 2018; 6(10): 821-32. http://doi.org/10.1016/S2213-8587(18)30025-1.