PDF
ePub
Citation
Print
Abstract
Dipeptidylpeptidase-4 (DPP-4) inhibitors are new glucose-lowering agents with mechanisms that differ from those of previous oral hypoglycemic agents (OHAs). DPP-4 inhibitors have shown a continuous glucose lowering effect (＞ 0.5%) when used in monotherapy as well as when used in combination with metformin, sulfonylurea, thiazolidinedione (TZD), insulin, and any other drug. In addition to improving glucose control, DPP-4 inhibitors have also shown a neutral effect on weight gain, improved β-cell function, and lowered the risk of hypoglycemia. Because of these advantages, DPP-4 inhibitors are widely used in the treatment of all patients with type 2 diabetes mellitus, but especially elderly patients. Therefore, more information regarding these strengths of DPP-4 inhibitors will lead to better treatment of patients with T2DM.
References
1. Drucker DJ. The role of gut hormones in glucose homeostasis. J Clin Invest. 2007; 117:24–32.
2. Russell-Jones D, Gough S. Recent advances in incretin-based therapies. Clin Endocrinol (Oxf). 2012; 77:489–99.
3. Scheen AJ. A review of gliptins in 2011. Expert Opin Pharmacother. 2012; 13:81–99.
4. Chia CW, Egan JM. Incretin-based therapies in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2008; 93:3703–16.
5. Monami M, Iacomelli I, Marchionni N, Mannucci E. Dipeptydil peptidase-4 inhibitors in type 2 diabetes: a metaanalysis of randomized clinical trials. Nutr Metab Cardiovasc Dis. 2010; 20:224–35.
6. Esposito K, Chiodini P, Bellastella G, Maiorino MI, Giugliano D. Proportion of patients at hba1c target ＜ 7% with eight classes of antidiabetic drugs in type 2 diabetes: systematic review of 218 randomized controlled trials with 78945 patients. Diabetes Obes Metab. 2012; 14:228–33.
7. Park H, Park C, Kim Y, Rascati KL. Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes: metaanalysis. Ann Pharmacother. 2012; 46:1453–69.
8. Bergman RN, Phillips LS, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest. 1981; 68:1456–67.
9. Blonde L, Dagogo-Jack S, Banerji MA, Pratley RE, Marcellari A, Braceras R, Purkayastha D, Baron M. Comparison of vildagliptin and thiazolidinedione as add-on therapy in patients inadequately controlled with metformin: results of the galiant trial–a primary care, type 2 diabetes study. Diabetes Obes Metab. 2009; 11:978–86.
10. McIntosh B, Cameron C, Singh SR, Yu C, Ahuja T, Welton NJ, Dahl M. Second-line therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a systematic review and mixed-treatment comparison metaanalysis. Open Med. 2011; 5:e35–48.
11. Scheen AJ. Dpp-4 inhibitors in the management of type 2 diabetes: a critical review of head-to-head trials. Diabetes Metab. 2012; 38:89–101.
12. Bonora E. Antidiabetic medications in overweight/obese patients with type 2 diabetes: drawbacks of current drugs and potential advantages of incretin-based treatment on body weight. Int J Clin Pract Suppl. 2007; 154:19–28.
13. Scheen AJ. Current management strategies for coexisting diabetes mellitus and obesity. Drugs. 2003; 63:1165–84.
14. Foley JE, Jordan J. Weight neutrality with the dpp-4 inhibitor, vildagliptin: mechanistic basis and clinical experience. Vasc Health Risk Manag. 2010; 6:541–8.
15. Cornell S. Differentiating among incretin therapies: a multiple-target approach to type 2 diabetes. J Clin Pharm Ther. 2012; 37:510–24.
16. Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP, Porte D Jr. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes. 1993; 42:1663–72.
17. Montanya E, Nacher V, Biarnes M, Soler J. Linear correlation between beta-cell mass and body weight throughout the lifespan in lewis rats: role of beta-cell hyperplasia and hypertrophy. Diabetes. 2000; 49:1341–6.
18. Pospisilik JA, Martin J, Doty T, Ehses JA, Pamir N, Lynn FC, Piteau S, Demuth HU, McIntosh CH, Pederson RA. Dipeptidyl peptidase iv inhibitor treatment stimulates beta-cell survival and islet neogenesis in streptozotocin-induced diabetic rats. Diabetes. 2003; 52:741–50.
19. Mu J, Woods J, Zhou YP, Roy RS, Li Z, Zycband E, Feng Y, Zhu L, Li C, Howard AD, Moller DE, Thornberry NA, Zhang BB. Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic beta-cell mass and function in a rodent model of type 2 diabetes. Diabetes. 2006; 55:1695–704.
20. Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2007; 9:194–205.
21. Seck T, Nauck M, Sheng D, Sunga S, Davies MJ, Stein PP, Kaufman KD, Amatruda JM. 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; 64:562–76.
22. van Genugten RE, van Raalte DH, Diamant M. Dipeptidyl peptidase-4 inhibitors and preservation of pancreatic islet-cell function: a critical appraisal of the evidence. Diabetes Obes Metab. 2012; 14:101–11.
23. Scherbaum WA, Schweizer A, Mari A, Nilsson PM, Lalanne G, Jauffret S, Foley JE. Efficacy and tolerability of vildagliptin in drug-naive patients with type 2 diabetes and mild hyperglycaemia. Diabetes Obes Metab. 2008; 10:675–82.
24. Kirby M, Yu DM, O'Connor S, Gorrell MD. Inhibitor selectivity in the clinical application of dipeptidyl peptidase-4 inhibition. Clin Sci (Lond). 2010; 118:31–41.
25. Richard KR, Shelburne JS, Kirk JK. Tolerability of dipeptidyl peptidase-4 inhibitors: a review. Clin Ther.
26. Chan JC, Scott R, Arjona Ferreira JC, Sheng D, Gonzalez E, Davies MJ, Stein PP, Kaufman KD, Amatruda JM, Williams-Herman D. Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency. Diabetes Obes Metab. 2008; 10:545–55.
27. Scheen AJ. Linagliptin for the treatment of type 2 diabetes (pharmacokinetic evaluation). Expert Opin Drug Metab Toxicol. 2011; 7:1561–76. 28. SSchweizer A, Dejager S, Foley JE, Shao Q, Kothny W. Clinical experience with vildagliptin in the management of type 2 diabetes in a patient population ＞/=75 years: a pooled analysis from a database of clinical trials. Diabetes Obes Metab. 2011; 13:55–64.
29. Barzilai N, Guo H, Mahoney EM, Caporossi S, Golm GT, Langdon RB, Williams-Herman D, Kaufman KD, Amatruda JM, Goldstein BJ, Steinberg H. Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Curr Med Res Opin. 2011; 27:1049–58.
30. Monami M, Ahren B, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and cardiovascular risk: a metaanalysis of randomized clinical trials. Diabetes Obes Metab. 2013; 15:112–20.
31. Monami M, Dicembrini I, Martelli D, Mannucci E. Safety of dipeptidyl peptidase-4 inhibitors: a metaanalysis of randomized clinical trials. Curr Med Res Opin. 2011; 27(Suppl 3):57–64.
32. Paolisso G, Monami M, Marfella R, Rizzo MR, Mannucci E. Dipeptidyl peptidase-4 inhibitors in the elderly: more benefits or risks? Adv Ther. 2012; 29:218–33.
XML Download