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Journal of Endocrinological Investigation

, Volume 30, Issue 7, pp 610–614 | Cite as

Dipeptidyl peptidase 4 (DPP-4) inhibitors and their role in Type 2 diabetes management

  • G. Crepaldi
  • M. Carruba
  • M. Comaschi
  • S. Del Prato
  • G. Frajese
  • G. Paolisso
Short Review

Abstract

Dipeptidyl peptidase 4 (DPP-4) inhibitors are a new pharmacological class of drugs for treating Type 2 diabetes. They improve the capacity of the organism to control glycemia by increasing the levels of active incretins. Their mechanism of action is thus radically different from those of other anti-diabetic drugs currently available. DDP-4 inhibitors use a physiological mechanism to control hyperglycemia, by stimulating the secretion of insulin from β-cells, decreasing the secretion of glucagon from pancreatic α-cells, and at the same time reducing the production of glucose by the liver. DDP-4 inhibitors have shown significant efficacy in maintaining reduced levels of glycosylated hemoglobin for up to 1 year. In vitro and animal studies have shown that they can inhibit apoptosis of β-cells and favor their regeneration and differentiation. The oral DPP-4 inhibitors vildagliptin, sitagliptin, and saxagliptin are efficacious both alone and in association with other oral anti-diabetic agents and may be administered in a single daily dose. Lastly, they have substantial advantages with respect to other anti-diabetic drugs, since they involve a low risk of hypoglycemia and do not affect body weight.

Key-words

Incretins insulin secretion Type 2 diabetes 

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References

  1. 1.
    Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004, 27: 1047–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Ahren B. Type 2 diabetes, insulin secretion and beta-cell mass. Curr Mol Med 2005, 5: 275–86.PubMedCrossRefGoogle Scholar
  3. 3.
    Dunning BE, Foley JE, Ahren B. Alpha cell function in health and disease: influence of glucagon-like peptide-1. Diabetologia 2005, 48: 1700–13.PubMedCrossRefGoogle Scholar
  4. 4.
    Ahren B, Schmitz O. GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. Horm Metab Res 2004, 36: 867–76.PubMedCrossRefGoogle Scholar
  5. 5.
    Deacon CF, Ahrén B, Holst JJ. Inhibitors of dipeptidyl peptidase IV: a novel approach for the prevention and treatment of Type 2 diabetes? Expert Opin Investig Drugs 2004, 13: 1091–102.PubMedCrossRefGoogle Scholar
  6. 6.
    Ahren B. Vildagliptin: an inhibitor of dipeptidyl peptidase-4 with antidiabetic properties. Expert Opin Investig Drugs 2006, 15: 431–42.PubMedCrossRefGoogle Scholar
  7. 7.
    Ahren B, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab 2004, 89: 2078–84.PubMedCrossRefGoogle Scholar
  8. 8.
    Mari A, Sallas WM, He YL, et al. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab 2005, 90: 4888–94.PubMedCrossRefGoogle Scholar
  9. 9.
    Burkey BF, Li X, Bolognese L, et al. Acute and chronic effects of the incretin enhancer vildagliptin in insulin-resistant rats. J Pharmacol Exp Ther 2005, 315: 688–95.PubMedCrossRefGoogle Scholar
  10. 10.
    Rolin B. The novel xanthine-based DPPIV inhibitor NN7201 and LAF237 improve glucose tolerance, but do not prevent progression of diabetes in Zucker diabetic fatty rats. Diabetes 2004, 53 (Suppl 2): A341.Google Scholar
  11. 11.
    Mika A. Acute DPP IV inhibition minimizes glucose and insulin responses to a glucose challenge in a diabetic mouse. Diabetes 2003, 52 (Suppl 1): A350.Google Scholar
  12. 12.
    Sorhede Winzell M, Ahren B. The high-fat fed mouse: a model for studying mechanism and treatment of impaired glucose tolerance and Type 2 diabetes. Diabetes 2004, 53 (Suppl 3): S215–9.CrossRefGoogle Scholar
  13. 13.
    Ahren B, Sorhede Winzell M, Burkey B, Hughes TE. Beta-cell expression of a dominant-negative HNF-1 alpha compromises the ability of inhibition of dipeptidyl peptidase-4 to elicita long-term augmentation of insulin secretion in mice. Eur J Pharmacol 2005, 521: 164–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Dardik B. NVP-LAF237, a dipeptidyl peptidase IV inhibitor, improves glucose tolerance and delays gastric emptying in obese insulin resistant Cynomolgus monkeys. Diabetes 2003, 52 (Suppl 1): A322Google Scholar
  15. 15.
    Duttaroy A, Voelker F, Zhang X, et al. The DPP-4 inhibitor vildagliptin increases β cell mass in rodents. Diabetologia 2005, 48 (Suppl 1): A178.Google Scholar
  16. 16.
    Ristic S, Byiers S, Foley J, Holmes D. Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabetes Obes Metab 2005, 7: 692–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Pratley RE, Jauffret-Kamel S, Galbreath E, Holmes D. Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes. Horm Metab Res 2006, 38: 423–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Ahren B. Gomis R, Standl E, Mills D, Schweizer A. Twelve-and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 2004, 27: 2874–80.Google Scholar
  19. 19.
    Garber A, Camisasca R, Ersham E, et al. Vildagliptin added to metformin improves glycemic control and may mitigate metformin-induced GI side effects in patients with type 2 diabetes (T2DM). Diabetes 2006, 55 (Suppl 1): A29 (abstract 121-OR).Google Scholar
  20. 20.
    Nathwani A. The use of Vildagliptin for treatment of patients with type 2 diabetes. Late breaking clinical study presented at: 66th Annual Scientific Session of the American Diabetes Association, San Diego, CA, 2005 (http://www.diabetesconnect.org/cgi-bin/store/webcasts_speaker).
  21. 21.
    Dejager S, Lebeaut A, Couturier A, Schweizer A. Sustained reduction in HbA1c during one-year treatment with vildagliptin in patients with type 2 diabetes (T2DM). Diabetes 2006, 55 (Suppl 1): A29 (abstract 120-OR).Google Scholar
  22. 22.
    Fonseca V, Dejager S, Albrecht D, Shirt L, Schweizer A. Vildagliptin as add-on to insulin in patients with type 2 diabetes (T2DM). Diabetes 2006, 55 (Suppl 1): A111 (abstract 467-P).Google Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2007

Authors and Affiliations

  • G. Crepaldi
    • 1
  • M. Carruba
    • 2
  • M. Comaschi
    • 3
  • S. Del Prato
    • 4
  • G. Frajese
    • 5
  • G. Paolisso
    • 6
  1. 1.Department of Medical and Surgical SciencesUniversity of PaduaPadovaItaly
  2. 2.Department of PharmacologyChemiotherapy and Medical Toxicology, LITA L. Sacco Hospital, School of Medicine, University of MilanMilan
  3. 3.Department of Internal MedicineWest Genoa HospitalGenoa
  4. 4.Department of Endocrinology and MetabolismUniversity of PisaPisa
  5. 5.Department of Internal MedicineUniversity of Rome Tor VergataRome
  6. 6.Departments of Geriatric and Metabolic Diseases, Experimental Medicine, and Clinical and Preventive MedicineSecond University of NaplesNaplesItaly

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