Therapeutic roadmap for sitagliptin Review article
Article Sidebar
Published:
Mar 1, 2026
Keywords:
type 2 diabetes, sitagliptin, metformin
Main Article Content
Abstract
Sitagliptin is a selective inhibitor of the DPP-4 peptidase enzyme, whose natural role in the body is the rapid breakdown of incretin hormones (GLP-1 and GIP). By blocking the DPP-4 enzyme, incretin hormones remain in the body longer. It has a moderately potent glucose-lowering effect and has a neutral effect on body weight. Sitagliptin’s advantage is its safety; there is no risk of hypoglycemia when used with sitagliptin. It is the most thoroughly studied gliptin in terms of its effectiveness in various drug combinations, drug tolerability, and safety in various patient groups, particularly in the elderly. It is the drug of choice for elderly people with diabetes at high risk of hypoglycemia and drug intolerance. Sitagliptin is firmly established in guidelines as a second- or third-line treatment. This article discusses the place of sitagliptin in current treatment recommendations for type 2 diabetes.
Article Details
How to Cite
Cyganek, K. (2026). Therapeutic roadmap for sitagliptin. Medycyna Faktow (J EBM), 19(4(69), 499-503. https://doi.org/10.24292/01.MF.0425.03
Issue
Section
Articles
Copyright by Medical Education. All rights reserved.
References
1. Davies MJ, Aroda VR, Collins BS et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022; 65(12): 1925-66. https://doi.org/10.1007/s00125-022-05787-2.
2. American Diabetes Association Position Statement. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes – 2026 Diabetes Care. 2026; 45(Suppl. 48): S52-76. https://doi.org/10.2337/dc24-S004.
3. Araszkiewicz A, Bandurska-Stankiewicz E, Borys S et al. Standards of Care in Diabetes. The position of Diabetes Poland – 2025. Current Topics in Diabetes. 2025; 5(1): 1-158. https://doi.org/10.5114/ctd/203685.
4. Nauck MA. Unraveling the science of incretin biology. Am J Med. 2009; 122(6 Suppl): S3-S10. https://doi.org/10.1016/j.amjmed.2009.03.012.
5. Esposito K, Chiodini P, Maiorino MI et al. Glycaemic durability with dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of long-term randomised controlled trials. BMJ. 2014; 4: e005442.
6. Sharma M, Beckley N, Nazareth I et al. Effectiveness of sitagliptin compared to sulfonylureas for type 2 diabetes mellitus inadequately controlled on metformin: a systematic review and meta-analysis. BMJ Open. 2017; 7: e017260. https://doi.org/10.1136/bmjopen-2017-017260.
7. Deng Y, Polley EC, Wallach JD et al. Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial. BMJMED. 2023; 2: e000419. https://doi.org/10.1136/ bmjmed-2022-000419.
8. Goossen K, Graber S. Longer term safety of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab. 2012; 14: 1061-72.
9. Janani L, Bamehr H, Tanha K et al. Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Drug Res. 2021; 71: 477-88.
10. Haddad F, Dokmak G, Bader M et al. A Comprehensive Review on Weight Loss Associated with Anti-Diabetic Medications. Life. 2023; 13: 1012. https://doi.org/10.3390/life13041012.
11. Kubota A, Maeda H, Kanamori A et al. Pleiotropic effects of sitagliptin in the treatment of type 2 diabetes mellitus patients. J Clin Med Res. 2012; 4: 309-13.
12. Shigematsu E, Yamakawa T, Kadonosono K et al. Effect of Sitagliptin on Lipid Profile in Patients With Type 2 Diabetes Mellitus. J Clin Med Res. 2014; 6(5): 327-35.
13. Monami M, Lamanna C, Desideri CM et al. DPP-4 inhibitors and lipids: systematic review and meta-analysis. Adv Ther. 2012; 29(1): 14-25.
14. Engel SS, Williams-Herman DE, Golm GT et al. Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis. Int J Clin Pract. 2010; 64(7): 984-90.
15. Eurich D, Simpson S, Senthilselvan A et al. Comparative safety and effectiveness of sitagliptin in patients with type 2 diabetes: retrospective population based cohort study. BMJ. 2013; 346: f2267.
16. Arjona Ferreira JC, Marre M, Barzilai N et al. Efficacy and safety of sitagliptin versus glipizide in patients with type 2 diabetes and moderate-tosevere chronic renal insufficiency. Diabetes Care. 2013; 36(5): 1067-73.
17. Roussel R, Duran-Garcia S, Zhang Y at al. Double-blind, randomized clinical trial comparing the efficacy and safety of continuing or discontinuing the dipeptidyl peptidase-4 inhibitor sitagliptin when initiating insulin glargine therapy in patients with type 2 diabetes: The Compo-SIT-I Study. Diabetes Obes Metab. 2019; 21: 781-90.
18. Mesri Alamdari N, Barghaman M, Roshanravan N et al. Comparison of the effects of empagliflozin and sitagliptin, as an add-on to metformin, on cardio-metabolic and glycemic parameters of patients with type 2 diabetes mellitus: a randomized, double-blind clinical trial. BMC Res Notes. 2025; 18(1): 339. https://doi.org/10.1186/s13104-025-07214-2.
19. Lee KA, Jin HY, Kim YJ et al. Real-world comparison of mono and dual combination therapies of metformin, sulfonylurea, and dipeptidyl peptidase-4 inhibitors using a common data model: a retrospective observational study. Medicine. 2022; 101(8): e28823.
20. Elhini SH, Hussien AK, Omran AA et al. Efficacy and safety profile of sitagliptin, vildagliptin, and metformin in newly diagnosed type 2 diabetic subjects. Clin Exp Pharmacol Physiol. 2021; 48(12): 1589-602.
21. Hong JH, Moon JS, Seong K et al. Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea and metformin: Third agent study. Diabetes Res Clin Pract. 2023; 203: 110872. https://doi.org/10.1016/j.diabres.2023.110872.
22. Zakaraia HG, Salem HF, Mostafa MAA et al. Adding empagliflozin to sitagliptin plus metformin vs. adding sitagliptin to empagliflozin plus metformin as triple therapy in Egyptian patients with type 2 diabetes: a 12-week open trial. Eur Rev Med Pharmacol Sci. 2023; 27(15): 7289-98.
23. Yaribeygi H, Mirmohammadkhani M, Rashidy-Pour A et al. Addition of sitagliptin to ongoing metformin improved metabolic profile and pancreatic function via normalizing inflammatory cytokines’ levels in patients with type 2 diabetes, a randomized double-blinded clinical trial. Expert Rev Endocrinol Metab. 2025; 20(6): 623-31. https://doi.org/10.1080/17446651.2025.2539252.
24. Park Y-H, Sohn M, Lee SY et al. Two-Year Therapeutic Efficacy and Safety of Initial Triple Combination of Metformin, Sitagliptin, and Empagliflozin in Drug-Naïve Type 2 Diabetes Mellitus Patients. Diabetes Metab J. 2024; 48: 253-64. https://doi.org/10.4093/dmj.2023.0128.
25. De Luca M, Arcopinto M, Bosco G et al. Patterns and Clinical Outcomes of Sitagliptin/Metformin Extended-Release in Internal Medicine: A Real-World Multicenter Italian Study. J Clin Med. 2026; 15: 927. https://doi.org/10.3390/jcm15030927.
2. American Diabetes Association Position Statement. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes – 2026 Diabetes Care. 2026; 45(Suppl. 48): S52-76. https://doi.org/10.2337/dc24-S004.
3. Araszkiewicz A, Bandurska-Stankiewicz E, Borys S et al. Standards of Care in Diabetes. The position of Diabetes Poland – 2025. Current Topics in Diabetes. 2025; 5(1): 1-158. https://doi.org/10.5114/ctd/203685.
4. Nauck MA. Unraveling the science of incretin biology. Am J Med. 2009; 122(6 Suppl): S3-S10. https://doi.org/10.1016/j.amjmed.2009.03.012.
5. Esposito K, Chiodini P, Maiorino MI et al. Glycaemic durability with dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of long-term randomised controlled trials. BMJ. 2014; 4: e005442.
6. Sharma M, Beckley N, Nazareth I et al. Effectiveness of sitagliptin compared to sulfonylureas for type 2 diabetes mellitus inadequately controlled on metformin: a systematic review and meta-analysis. BMJ Open. 2017; 7: e017260. https://doi.org/10.1136/bmjopen-2017-017260.
7. Deng Y, Polley EC, Wallach JD et al. Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial. BMJMED. 2023; 2: e000419. https://doi.org/10.1136/ bmjmed-2022-000419.
8. Goossen K, Graber S. Longer term safety of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab. 2012; 14: 1061-72.
9. Janani L, Bamehr H, Tanha K et al. Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Drug Res. 2021; 71: 477-88.
10. Haddad F, Dokmak G, Bader M et al. A Comprehensive Review on Weight Loss Associated with Anti-Diabetic Medications. Life. 2023; 13: 1012. https://doi.org/10.3390/life13041012.
11. Kubota A, Maeda H, Kanamori A et al. Pleiotropic effects of sitagliptin in the treatment of type 2 diabetes mellitus patients. J Clin Med Res. 2012; 4: 309-13.
12. Shigematsu E, Yamakawa T, Kadonosono K et al. Effect of Sitagliptin on Lipid Profile in Patients With Type 2 Diabetes Mellitus. J Clin Med Res. 2014; 6(5): 327-35.
13. Monami M, Lamanna C, Desideri CM et al. DPP-4 inhibitors and lipids: systematic review and meta-analysis. Adv Ther. 2012; 29(1): 14-25.
14. Engel SS, Williams-Herman DE, Golm GT et al. Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis. Int J Clin Pract. 2010; 64(7): 984-90.
15. Eurich D, Simpson S, Senthilselvan A et al. Comparative safety and effectiveness of sitagliptin in patients with type 2 diabetes: retrospective population based cohort study. BMJ. 2013; 346: f2267.
16. Arjona Ferreira JC, Marre M, Barzilai N et al. Efficacy and safety of sitagliptin versus glipizide in patients with type 2 diabetes and moderate-tosevere chronic renal insufficiency. Diabetes Care. 2013; 36(5): 1067-73.
17. Roussel R, Duran-Garcia S, Zhang Y at al. Double-blind, randomized clinical trial comparing the efficacy and safety of continuing or discontinuing the dipeptidyl peptidase-4 inhibitor sitagliptin when initiating insulin glargine therapy in patients with type 2 diabetes: The Compo-SIT-I Study. Diabetes Obes Metab. 2019; 21: 781-90.
18. Mesri Alamdari N, Barghaman M, Roshanravan N et al. Comparison of the effects of empagliflozin and sitagliptin, as an add-on to metformin, on cardio-metabolic and glycemic parameters of patients with type 2 diabetes mellitus: a randomized, double-blind clinical trial. BMC Res Notes. 2025; 18(1): 339. https://doi.org/10.1186/s13104-025-07214-2.
19. Lee KA, Jin HY, Kim YJ et al. Real-world comparison of mono and dual combination therapies of metformin, sulfonylurea, and dipeptidyl peptidase-4 inhibitors using a common data model: a retrospective observational study. Medicine. 2022; 101(8): e28823.
20. Elhini SH, Hussien AK, Omran AA et al. Efficacy and safety profile of sitagliptin, vildagliptin, and metformin in newly diagnosed type 2 diabetic subjects. Clin Exp Pharmacol Physiol. 2021; 48(12): 1589-602.
21. Hong JH, Moon JS, Seong K et al. Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea and metformin: Third agent study. Diabetes Res Clin Pract. 2023; 203: 110872. https://doi.org/10.1016/j.diabres.2023.110872.
22. Zakaraia HG, Salem HF, Mostafa MAA et al. Adding empagliflozin to sitagliptin plus metformin vs. adding sitagliptin to empagliflozin plus metformin as triple therapy in Egyptian patients with type 2 diabetes: a 12-week open trial. Eur Rev Med Pharmacol Sci. 2023; 27(15): 7289-98.
23. Yaribeygi H, Mirmohammadkhani M, Rashidy-Pour A et al. Addition of sitagliptin to ongoing metformin improved metabolic profile and pancreatic function via normalizing inflammatory cytokines’ levels in patients with type 2 diabetes, a randomized double-blinded clinical trial. Expert Rev Endocrinol Metab. 2025; 20(6): 623-31. https://doi.org/10.1080/17446651.2025.2539252.
24. Park Y-H, Sohn M, Lee SY et al. Two-Year Therapeutic Efficacy and Safety of Initial Triple Combination of Metformin, Sitagliptin, and Empagliflozin in Drug-Naïve Type 2 Diabetes Mellitus Patients. Diabetes Metab J. 2024; 48: 253-64. https://doi.org/10.4093/dmj.2023.0128.
25. De Luca M, Arcopinto M, Bosco G et al. Patterns and Clinical Outcomes of Sitagliptin/Metformin Extended-Release in Internal Medicine: A Real-World Multicenter Italian Study. J Clin Med. 2026; 15: 927. https://doi.org/10.3390/jcm15030927.