Sitagliptin – is there a place for it in modern treatment of type 2 diabetes? Review article
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Published:
Jun 30, 2023
Keywords:
type 2 diabetes, DPP-4 inhibitor, sitagliptin, incretins
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Abstract
Type 2 diabetes (DM2) is a growing clinical problem and inadequate metabolic control of the disease in many patients leads to the search for new therapy methods. In recent years, new drugs have been introduced to the therapy, the mechanism of action of which is based on the use of the incretin axis to optimize the treatment of diabetes. Among the drugs that use the potential of the incretin effect, there are dipeptidyl peptidase 4 (DPP-4) inhibitors.
This article covers the basics of the concept of using the incretin effect in the treatment of DM, the basic pharmacological profile of sitagliptin, and important clinical studies on the effectiveness and safety of the drug. This review is intended to summarize sitagliptin’s position as a well-tolerated, relatively effective, safe drug, also for patients with moderate renal and hepatic impairment and a drug with a low risk of causing hypoglycemia.
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How to Cite
KosińskiM. (2023). Sitagliptin – is there a place for it in modern treatment of type 2 diabetes?. Medycyna Faktow (J EBM), 16(2(59), 219-224. https://doi.org/10.24292/01.MF.0223.14
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References
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8. Vilsbøll T, Holst JJ. Incretins, insulin secretion and Type 2 diabetes mellitus. Diabetologia. 2004; 47(3): 357-66. http://doi.org/10.1007/s00125-004-1342-6.
9.Nauck MA, Heimesaat MM, Orskov C et al. Preserved incretin activity of glucagon-like peptide 1 7-36 amide but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993; 91(1): 301-7. http://doi.org/10.1172/JCI116186.
10. Vilsbøll T, Krarup T, Deacon CF et al. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001; 50(3): 609-13. http://doi.org/10.2337/diabetes.50.3.609.
11. Lankas GR, Leiting B, Roy RS et al. Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes. 2005; 54(10): 2988-94. http://doi.org/10.2337/diabetes.54.10.2988.
12. Kim D, Wang L, Beconi M et al. (2R)-4-oxo-4-3-(trifluoromethyl)-5,6-dihydro1,2,4triazolo4,3-apyrazin-7(8H)-yl-1-(2,4,5-trifluorophenyl)butan-2- amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem. 2005; 48(1): 141-51. http://doi.org/10.1021/jm0493156.
13. Herman GA, Stein PP, Thornberry NA et al. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: focus on sitagliptin. Clin Pharmacol Ther. 2007; 81(5): 761-7. http://doi.org/10.1038/sj.clpt.6100167.
14. Palalau AI, Tahrani AA, Piya MK et al. DPP-4 inhibitors in clinical practice. Postgrad Med. 2009; 121(6): 70-100. http://doi.org/10.3810/pgm.2009.11.2079.
15. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006; 368(9548): 1696-705. http://doi.org/10.1016/S0140-6736(06)69705-5.
16.Hanefeld M, Herman GA, Wu M et al. Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of patients with type 2 diabetes. Curr Med Res Opin. 2007; 23(6): 1329-39. http://doi.org/10.1185/030079907X188152.
17. Goldstein BJ, Feinglos MN, Lunceford JK et al. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007; 30(8): 1979-87. http://doi.org/10.2337/dc07-0627.
18.Migoya EM, Bergeron R, Miller JL et al. Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. Clin Pharmacol Ther. 2010; 88(6): 801-8. http://doi.org/10.1038/clpt.2010.184.
19.Mohan V, Yang W, Son H-Y et al. Efficacy and safety of sitagliptin in the treatment of patients with type 2 diabetes in China, India, and Korea. Diabetes Res Clin Pract. 2009; 83(1): 106-16. http://doi.org/10.1016/j.diabres.2008.10.009.
20. Raz I, Hanefeld M, Xu L et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia. 2006; 49(11): 2564-71. http://doi.org/10.1007/s00125-006-0416-z.
21. Charbonnel B, Karasik A, Liu J et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006; 29(12): 2638-43. http://doi.org/10.2337/dc06-0706.
22.Bergenstal RM, Wysham C, MacConell L et al. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010; 376(9739): 431-9. http://doi.org/10.1016/S0140-6736(10)60590-9.
23. Hermansen K, Kipnes M, Luo E et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007; 9(5): 733-45. http://doi.org/10.1111/j.1463-1326.2007.00744.x.
24. Rosenstock J, Brazg R, Andryuk PJ et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2006; 28(10): 1556-68. http://doi.org/10.1016/j.clinthera.2006.10.007.
25. Vilsbøll T, Rosenstock J, Yki-Järvinen H et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2010; 12(2): 167-77. http://doi.org/10.1111/j.1463-1326.2009.01173.x.
26. Seck T, Nauck M, Sheng D et al. Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2-year study. Int J Clin Pract. 2010; 64(5): 562-76. http://doi.org/10.1111/j.1742-1241.2010.02353.x.
27. Aschner P, Katzeff HL, Guo H et al. Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes. Diabetes Obes Metab. 2010; 12(3): 252-61. http://doi.org/10.1111/j.1463-1326.2009.01187.x.
28.Arechavaleta R, Seck T, Chen Y et al. Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2011; 13(2): 160-8. http://doi.org/10.1111/j.1463-1326.2010.01334.x.
29. Scheen AJ, Charpentier G, Ostgren CJ et al. Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus. Diabetes Metab Res Rev. 2010; 26(7): 540-9. http://doi.org/10.1002/dmrr.1114.
30. Pratley RE, Nauck M, Bailey T et al. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010; 375(9724): 1447-56. http://doi.org/10.1016/S0140-6736(10)60307-8.
31. DeFronzo RA, Okerson T, Viswanathan P et al. Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study. Curr Med Res Opin. 2008; 24(10): 2943-52. http://doi.org/10.1185/03007990802418851.
32. Green JB, Bethel MA, Armstrong PW et al. 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.
33. Nauck M, Stöckmann F, Ebert R et al. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986; 29(1): 46-52.
2. Perley MJ, Kipnis DM. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. J Clin Invest. 1967; 46(12): 1954-62. http://doi.org/10.1172/JCI105685.
3. Schmidt WE, Siegel EG, Creutzfeldt W. Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets. Diabetologia. 1985; 28(9): 704-7. http://doi.org/10.1007/BF00291980.
4. Ahrén B. Gut peptides and type 2 diabetes mellitus treatment. Curr Diab Rep. 2003; 3(5): 365-72. http://doi.org/10.1007/s11892-003-0079-9.
5. Ehses JA, Casilla VR, Doty T et al. Glucose-dependent insulinotropic polypeptide promotes beta-(INS-1) cell survival via cyclic adenosine monophosphate-mediated caspase-3 inhibition and regulation of p38 mitogen-activated protein kinase. Endocrinology. 2003; 144(10): 4433-45. http://doi.org/10.1210/en.2002-0068.
6. Drucker DJ. Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology. 2002; 122(2): 531-44. http://doi.org/10.1053/gast.2002.31068.
7. Farilla L, Bulotta A, Hirshberg B et al. Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology. 2003; 144(12): 5149-58. http://doi.org/10.1210/en.2003-0323.
8. Vilsbøll T, Holst JJ. Incretins, insulin secretion and Type 2 diabetes mellitus. Diabetologia. 2004; 47(3): 357-66. http://doi.org/10.1007/s00125-004-1342-6.
9.Nauck MA, Heimesaat MM, Orskov C et al. Preserved incretin activity of glucagon-like peptide 1 7-36 amide but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993; 91(1): 301-7. http://doi.org/10.1172/JCI116186.
10. Vilsbøll T, Krarup T, Deacon CF et al. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001; 50(3): 609-13. http://doi.org/10.2337/diabetes.50.3.609.
11. Lankas GR, Leiting B, Roy RS et al. Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes. 2005; 54(10): 2988-94. http://doi.org/10.2337/diabetes.54.10.2988.
12. Kim D, Wang L, Beconi M et al. (2R)-4-oxo-4-3-(trifluoromethyl)-5,6-dihydro1,2,4triazolo4,3-apyrazin-7(8H)-yl-1-(2,4,5-trifluorophenyl)butan-2- amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem. 2005; 48(1): 141-51. http://doi.org/10.1021/jm0493156.
13. Herman GA, Stein PP, Thornberry NA et al. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: focus on sitagliptin. Clin Pharmacol Ther. 2007; 81(5): 761-7. http://doi.org/10.1038/sj.clpt.6100167.
14. Palalau AI, Tahrani AA, Piya MK et al. DPP-4 inhibitors in clinical practice. Postgrad Med. 2009; 121(6): 70-100. http://doi.org/10.3810/pgm.2009.11.2079.
15. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006; 368(9548): 1696-705. http://doi.org/10.1016/S0140-6736(06)69705-5.
16.Hanefeld M, Herman GA, Wu M et al. Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of patients with type 2 diabetes. Curr Med Res Opin. 2007; 23(6): 1329-39. http://doi.org/10.1185/030079907X188152.
17. Goldstein BJ, Feinglos MN, Lunceford JK et al. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007; 30(8): 1979-87. http://doi.org/10.2337/dc07-0627.
18.Migoya EM, Bergeron R, Miller JL et al. Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. Clin Pharmacol Ther. 2010; 88(6): 801-8. http://doi.org/10.1038/clpt.2010.184.
19.Mohan V, Yang W, Son H-Y et al. Efficacy and safety of sitagliptin in the treatment of patients with type 2 diabetes in China, India, and Korea. Diabetes Res Clin Pract. 2009; 83(1): 106-16. http://doi.org/10.1016/j.diabres.2008.10.009.
20. Raz I, Hanefeld M, Xu L et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia. 2006; 49(11): 2564-71. http://doi.org/10.1007/s00125-006-0416-z.
21. Charbonnel B, Karasik A, Liu J et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006; 29(12): 2638-43. http://doi.org/10.2337/dc06-0706.
22.Bergenstal RM, Wysham C, MacConell L et al. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010; 376(9739): 431-9. http://doi.org/10.1016/S0140-6736(10)60590-9.
23. Hermansen K, Kipnes M, Luo E et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007; 9(5): 733-45. http://doi.org/10.1111/j.1463-1326.2007.00744.x.
24. Rosenstock J, Brazg R, Andryuk PJ et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2006; 28(10): 1556-68. http://doi.org/10.1016/j.clinthera.2006.10.007.
25. Vilsbøll T, Rosenstock J, Yki-Järvinen H et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2010; 12(2): 167-77. http://doi.org/10.1111/j.1463-1326.2009.01173.x.
26. Seck T, Nauck M, Sheng D et al. Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2-year study. Int J Clin Pract. 2010; 64(5): 562-76. http://doi.org/10.1111/j.1742-1241.2010.02353.x.
27. Aschner P, Katzeff HL, Guo H et al. Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes. Diabetes Obes Metab. 2010; 12(3): 252-61. http://doi.org/10.1111/j.1463-1326.2009.01187.x.
28.Arechavaleta R, Seck T, Chen Y et al. Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2011; 13(2): 160-8. http://doi.org/10.1111/j.1463-1326.2010.01334.x.
29. Scheen AJ, Charpentier G, Ostgren CJ et al. Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus. Diabetes Metab Res Rev. 2010; 26(7): 540-9. http://doi.org/10.1002/dmrr.1114.
30. Pratley RE, Nauck M, Bailey T et al. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010; 375(9724): 1447-56. http://doi.org/10.1016/S0140-6736(10)60307-8.
31. DeFronzo RA, Okerson T, Viswanathan P et al. Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study. Curr Med Res Opin. 2008; 24(10): 2943-52. http://doi.org/10.1185/03007990802418851.
32. Green JB, Bethel MA, Armstrong PW et al. 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.
33. Nauck M, Stöckmann F, Ebert R et al. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986; 29(1): 46-52.