Strong evidence exists demonstrating the benefits of tight glycemic control in type 1 and type 2 diabetes mellitus patients, but glycemic goals are not adequately achieved for many patients. Advancement in the knowledge surrounding the physiology of endogenous glucoregula- tory peptide hormones, such as glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, has led to new therapeutic targets for the treatment of type 2 diabetes mellitus. Dipeptidyl peptidase-4 (DPP-4) inhibitors provide practitioners with a novel mechanism of action to use for combination therapies for the treatment of type 2 diabetes mellitus. This article, part 3 of a 3-part series, reviews the new class of medications known as DPP-4 inhibitors as well as discusses a future buccal insulin formulation, Oral-Lyn™, on the horizon for the treatment of diabetes mellitus.
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References
1.
Centers for Disease Control and Prevention.National Diabetes Fact Sheet: General Information and National Estimates on Diabetes in the United States, 2005. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2005.
2.
World Health Organization.Diabetes: What Is Diabetes? Available at: http:www.who.int/mediacentre/factsheets/fs312/en/ . Accessed August 24, 2007.
3.
Koro CE, Bowlin SJ, Bourgeois N., Fedder DOGlycemic control from 1988 to 2000 among U.S. adults diagnosed with type 2 diabetes: a preliminary report. Diabetes Care. 2004;27: 17-20.
4.
Diabetes Control and Complications Trial Research Group.The effect of intensive treatment of diabetes on development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986.
5.
UK Prospective Diabetes Study (UKPDS) Group.Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complication in patients with type 2 diabetes (UKPDS 33). Lancet. 1998 ;352:837-853.
6.
Cefalu WTEvaluation of alternative strategies for optimizing glycemia: progress to date. Am J Med. 2002;113:23S-35S.
7.
Januvia pricing information. Available at: http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=00006027731&trx=1Z5006. Accessed August 24, 2007.
8.
Deacon CF, Holst JJDipeptidyl peptidase IV inhibitors: a promising new therapeutic approach for the management of type 2 diabetes. Int J Biochem Cell Biol . 2006;38:831-844.
9.
Kim D., Wang L., Beconi M., et al. (2R)4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-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 Clin Endocrinol Metab. 2006;91:4612-4619.
10.
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;54:2988-2994.
Vincent SH, Reed JR, Bergman AJ, et al. Metabolism and excretion of the DPP-4 inhibitor [14C]sitagliptin in humans. Drug Metab Dispos. In press.
13.
Stevens C., Bergman AJ, Liu Q., et al. Lack of clinically significant effect of moderate hepatic insufficiency on the pharmacokinetics of MK-0431 (sitagliptin), a dipeptidyl-peptidase-IV inhibitor [abstract PII-49]. Clin Pharmacol Ther. 2006;79:P49.
14.
Aschner P., Kipnes M., Lunceford M., Sanchez M., Mickel C., Williams-Herman DEEffect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006;29:2632-2637.
15.
Aschner P., Kipnes M., Lunceford J., et al. Sitagliptin monotherapy improved glycemic control in the fasting and postprandial states and beta-cell function after 24 weeks in patients with type 2 diabetes (T2DM) [abstract]. Diabetes. 2006;55(suppl 1):A462. Abstract PO-1995.
16.
Charbonnel B., Karasik A., Liu J., Wu M., Meininger G.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;29:2638-2643.
17.
Williams-Herman D., Goldstein BJ, Feinglos MN, Lunceford, Johnson J.Initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin provides substantial glycemic improvements and Hba1c goal attainment in patients with type 2 diabetes mellitus (T2DM) [abstract]. Diabetes Med. 2006;23(suppl 4):319.
18.
Nauck M., Meininger G., Sheng D., Terranella L., Stein P.Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared to the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obesity Metab. 2007;9:194-205.
19.
Rosenstock J., Brazg R., Andryuk PJ, Lu K., Stein P.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;28:1556-1568.
20.
Rosenstock J., Brazg R., Andryuk PJ, et al. Addition of sitagliptin to pioglitazone improved glycemic control with neutral weight effect over 24 weeks in inadequately controlled type 2 diabetes (T2DM) [poster 556-P]. Presented at: 66th Annual American Diabetes Association Scientific Sessions Meeting; June 9-13, 2006; Washington, DC.
21.
Karasik A., Charbonnel B., Liu J., et al. Sitagliptin added to ongoing metformin therapy enhanced glycemic control and beta-cell function in patients with type 2 diabetes [poster 501-P] . Presented at: 66th Annual American Diabetes Association Scientific Sessions Meeting; June 9-13, 2006; Washington, DC.
22.
Scott R., Wu M., Sanchez M., et al. Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes . Int J Clin Pract. 2007;61:171-180.
Ahren B., Gomis R., Standl E., et al. Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care. 2004;27:2874-2880.
25.
He YL, Sabo R., Balez S., et al. Absolute bioavailability of vildagliptin in healthy subjects . Clin Pharmacol Ther. 2006;79:38.
26.
He YL, Balch A., Campestrini J., et al. Pharmacokinetics and pharmacodynamics of the DPP-4 inhibitor, LAF237, in patients with type 2 diabetes. Clin Pharmacol Ther. 2005;77:56.
27.
Barilla D., He Y., Balez S., et al. No pharmacokinetic interactions or acute clinical safety issues preclude combination of the DPP-4 inhibitor LAF237 with glyburide. Diabetes. 2004;53(suppl 2):470.
28.
Hughes TE, Mone MD, Russell ME, et al. NVP-DPP728 (1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine), a slow-binding inhibitor of dipeptidyl peptidase IV. Biochemistry (Mosc). 1999;38:11597-11603.
29.
Nathwani A.The use of vildagliptin for treatment of patients with type 2 diabetes mellitus . Presented at: American Diabetes Association 66th Scientific Sessions; June 9-13, 2006; Washington, DC.
30.
He Y-LL , Sabo R., Wang Y., et al. The influence of hepatic impairment on the pharmacokinetics of vildagliptin [abstract 2024-PO]. Diabetes. 2006;55(suppl 1):A4469.
31.
Serra DB, He YL, Wang Y., et al. Combination of the DPP-4 inhibitor vildagliptin (LAF237) with pioglitazone is safe and well tolerated with no pharmacokinetic interaction . Diabetes. 2005; 54(suppl 1):528-529.
32.
He YL, Sabo R., Picard F., et al. Lack of pharmacokinetic interaction between vildagliptin and metformin in patients with type 2 diabetes. Clin Pharmacol Ther. 2006;79:62.
33.
Pratley RE, Jauffret-Kamel S., Galbreath E., et al. Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes. Horm Metab Res. 2006;38:423-428.
34.
Ristic S., Byiers S., Foley J., et al. Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabetes Obes Metab. 2005;7:692-698.
35.
Mimori N., Terao S., Holmes D.Vildagliptin improves glucose control as evidenced by HbA1c after 12 weeks therapy in Japanese patients with type 2 diabetes [abstract 527-P]. Presented at: American Diabetes Association 66th Scientific Sessions ; June 9-13, 2006; Washington, DC.
36.
Baron MA, Rosenstock J., Bassiri B., et al. Efficacy of vildagliptin combined with pioglitazone in patients with type 2 diabetes [abstract 0801]. Diabetologia. 2006;49(suppl 1):A111.
37.
Fonseca V., DeJager S., Albrecht D., et al. Vildagliptin as add-on to insulin in patients with type 2 diabetes (T2DM) [abstract 467-P]. Diabetes. 2006;55(suppl 1):A111.
Ristic S., Byiers S., Foley J., et al. Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabetes Obes Metab. 2005;7:423-428.
40.
Campbell K. , Baker D.Getting past the sticker shock of drugs [guest editorial]. DOC News. June 2006:4.
41.
Cernea S., Kidron M., Wohlgelernter J., Modi P., Raz I.Dose-response relationship of oral insulin spray in healthy subjects. Diabetes Care. 2005;28:1353-1357.
42.
Guevara-Aguirre J., Guevara-Aguirre M., Saavedra J.Oral insulin (Oral-Lyn™) 6-month lunchtime replacement in juvenile type-1 DM [abstract 302]. Presented at: AACE Annual Meeting; April 11-15, 2007; Seattle, WA.
43.
Guevara-Aguirre J., Guevara-Aguirre M., Saavedra J.Regular insulin replacement by oral insulin at mealtime in type-1 DM [abstract 360]. Presented at: AACE Annual Meeting; April 11-15, 2007; Seattle, WA.
