Linagliptin as add-on therapy for type 2 diabetes - An overview

Drugs of Today

Volumn 48, Issue 10, 2012, Pages 645-654

  Brown, D X ^a   Choudhury, M ^a   Evans, M ^a  

^a LLANDOUGH HOSPITAL   (United Kingdom)

Author keywords

Diabetes; Dipeptidyl peptidase 4; Glucagon release; Insulin secretion

Indexed keywords

ALOGLIPTIN; DIGOXIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; ETHINYLESTRADIOL; GASTRIC INHIBITORY POLYPEPTIDE; GLIBENCLAMIDE; GLIMEPIRIDE; GLUCAGON LIKE PEPTIDE 1; INCRETIN; KETOCONAZOLE; LEVONORGESTREL; LINAGLIPTIN; METFORMIN; PLACEBO; RIFAMPICIN; RITONAVIR; SAXAGLIPTIN; SIMVASTATIN; SITAGLIPTIN; SULFONYLUREA; VILDAGLIPTIN; WARFARIN;

ADD ON THERAPY; AREA UNDER THE CURVE; DIABETIC PATIENT; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CONTRAINDICATION; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG INDICATION; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENCY; DRUG STRUCTURE; DRUG TOLERABILITY; GLUCAGON RELEASE; GLYCEMIC CONTROL; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; INSULIN RELEASE; INSULIN RESPONSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONHUMAN; PATHOGENESIS; REVIEW; SIDE EFFECT; WEIGHT GAIN;

DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DRUG INTERACTIONS; HUMANS; PURINES; QUINAZOLINES;

EID: 84869210962     PISSN: 16993993     EISSN: 16994019     Source Type: Journal    
DOI: 10.1358/dot.2012.48.10.1860771     Document Type: Review

References (43)

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(5): 1047-53. (Pubitemid 38579764)
2. Knop, F.K., Vilsboll, T., Hojberg, P.V. et al. Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? Diabetes 2007, 56(8): 1951-9. (Pubitemid 47195814)
3. Holst, J.J., Vilsboll, T., Deacon, C.F. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 2009, 297(1-2): 127-36.
4. McIntyre, N., Holdsworth, C.D., Turner, D.S. New interpretation of oral glucose tolerance. Lancet 1964, 2(7349): 20-1.
5. Drucker, D.J., Nauck, M.A. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006, 368(9548): 1696-705. (Pubitemid 46048557)
6. Barnett, A. DPP-4 inhibitors and their potential role in the management of type 2 diabetes. Int J Clin Pract 2006, 60(11): 1454-70. (Pubitemid 44560347)
7. Thornberry, N.A., Gallwitz, B. Mechanism of action of inhibitors of dipeptidyl-peptidase-4 (DPP-4). Best Pract Res Clin Endocrinol Metab 2009, 23(4): 479-86.
8. Barnett, A.H. Linagliptin: a novel dipeptidyl peptidase 4 inhibitor with a unique place in therapy. Adv Ther 2011, 28(6): 447-59.
9. Forst, T., Uhlig-Laske, B., Ring, A., Ritzhaupt, A., Graefe-Mody, U., Dugi, K.A. The oral DPP-4 inhibitor linagliptin significantly lowers HbA1c after 4 weeks of treatment in patients with type 2 diabetes mellitus. Diabetes Obes Metab 2011, 13(6): 542-50.
10. Villhauer, E.B., Brinkman, J.A., Naderi, G.B. et al. 1-[[(3-Hydroxy-1- adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem 2003, 46(13): 2774-89. (Pubitemid 36702545)
11. Augeri, D.J., Robl, J.A., Betebenner, D.A. et al. Discovery and preclinical profile of saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 2005, 48(15): 5025-37. (Pubitemid 41033142)
12. 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 Med Chem 2005, 48(1): 141-51. (Pubitemid 40105255)
13. Jose, T., Inzucchi, S.E. Cardiovascular effects of the DPP-4 inhibitors. Diab Vasc Dis Res 2012, 9(2): 109-16.
14. Deacon, C.F., Holst, J.J. Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes. Expert Opin Investig Drugs 2010, 19(1): 133-40.
15. Stulc, T., Sedo, A. Inhibition of multifunctional dipeptidyl peptidase-IV: is there a risk of oncological and immunological adverse effects? Diabetes Res Clin Pract 2010, 88(2): 125-31.
16. Thomas, L., Eckhardt, M., Langkopf, E., Tadayyon, M., Himmelsbach, F., Mark, M. (R)-8-(3-Amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl- quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J Pharmacol Exp Ther 2008, 325(1): 175-82. (Pubitemid 351439162)
17. 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. (Pubitemid 37476040)
18. Duttaroy, A., Voelker, F., Merriam, K. et al. The DPP-4 inhibitor vildagliptin increases pancreatic beta cell mass in neonatal rats. Eur J Pharmacol 2011, 650(2-3): 703-7.
19. Lim, E.L., Hollingsworth, K.G., Aribisala, B.S., Chen, M.J., Mathers, J.C., Taylor, R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011, 54(10): 2506-14.
20. Schurmann, C., Linke, A., Engelmann-Pilger, K. et al. The dipeptidyl peptidase-4 inhibitor linagliptin attenuates inflammation and accelerates epithelialization in wounds of diabetic ob/ob mice. J Pharmacol Exp Ther 2012, 342(1): 71-80.
21. Kern, M., Kloting, N., Niessen, H.G. et al. Linagliptin improves insulin sensitivity and hepatic steatosis in diet-induced obesity. PLoS One 2012, 7(6): e38744.
22. Patel, C.G., Li, L., Girgis, S., Kornhauser, D.M., Frevert, E.U., Boulton, D.W. Two-way pharmacokinetic interaction studies between saxagliptin and cytochrome P450 substrates or inhibitors: simvastatin, diltiazem extended-release, and ketoconazole. Clin Pharmacol 2011, 3: 13-25.
23. Graefe-Mody, U., Retlich, S., Friedrich, C. Clinical pharmacokinetics and pharmacodynamics of linagliptin. Clin Pharmacokinet 2012, 51(7): 411-27.
24. Blech, S., Ludwig-Schwellinger, E., Grafe-Mody, E.U., Withopf, B., Wagner, K. The metabolism and disposition of the oral dipeptidyl peptidase-4 inhibitor, linagliptin, in humans. Drug Metab Dispos 2010, 38(4): 667-78.
25. European Medicines Agency. Summary of Product Characteristics: Linagliptin. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR--- Product-Information/human/002110/WC500115745.pdf. Accessed September 28, 2012.
26. Barnett, A.H., Harper, R., Toorawa, Dong, H. Linagliptin monotherapy improves glycaemic control in type 2 diabetes patients for whom metformin therapy is inappropriate. 46th EASD (Sept 20-24, Stockholm) 2010, Abst 823.
27. BI 1356 (linagliptin) in combination with metformin and a sulphonylurea in type 2 diabetes (NCT00602472). ClinicalTrials.gov Web site, Accessed September 28, 2012.
28. Taskinen, M.R., Rosenstock, J., Tamminen, I., Kubiak, R., Patel, S., Dugi, K.A., Woerle, H.J. Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab 2011, 13(1): 65-74.
29. Gallwitz, B., Rosenstock, J., Rauch, T. et al. 2-Year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet 2012, 380(9840): 475-83.
30. de Boer, I.H., Rue, T.C., Hall, Y.N., Heagerty, P.J., Weiss, N.S., Himmelfarb, J. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA 2011, 305(24): 2532-9.
31. Graefe-Mody, U., Friedrich, C., Port, A. et al. Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin. Diabetes Obes Metab 2011, 13(10): 939-46.
32. Graefe-Mody, U., Rose, P., Ring, A., Zander, K., Iovino, M., Woerle, H.-J. Assessment of the pharmacokinetic interaction between the novel DPP-4 inhibitor linagliptin and a sulfonylurea, glyburide, in healthy subjects. Drug Metab Pharmacokinet 2011, 26(2): 123-9.
33. Graefe-Mody, U., Huettner, S., Stahle, H., Ring, A., Dugi, K.A. Effect of linagliptin (BI 1356) on the steady-state pharmacokinetics of simvastatin. Int J Clin Pharmacol Ther 2010, 48(6): 367-74.
34. Graefe-Mody, E.U., Brand, T., Ring, A., Withopf, B., Stangier, J., Iovino, M., Woerle, H.J. Effect of linagliptin on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. Int J Clin Pharmacol Ther 2011, 49(5): 300-10.
35. Friedrich, C., Ring, A., Brand, T., Sennewald, R., Graefe-Mody, E.U., Woerle, H.J. Evaluation of the pharmacokinetic interaction after multiple oral doses of linagliptin and digoxin in healthy volunteers. Eur J Drug Metab Pharmacokinet 2011, 36(1): 17-24.
36. Friedrich, C., Port, A., Ring, A., Graefe-Mody, U., Giessmann, T., Iovino, M., Woerle, H.J. Effect of multiple oral doses of linagliptin on the steady-state pharmacokinetics of a combination oral contraceptive in healthy female adults: an open-label, two-period, fixed-sequence, multiple-dose study. Clin Drug Investig 2011, 31(9): 643-53.
37. CAROLINA: Cardiovascular outcome study of linagliptin versus glimepiride in patients with type 2 diabetes (NCT01243424). ClinicalTrials.gov Web site, Accessed September 28, 2012.
38. Horie, Y., Kanada, S., Watada, H. et al. Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor linagliptin: a 4-week multicenter, randomized, double-blind, placebo-controlled phase IIa study in Japanese type 2 diabetes patients. Clin Ther 2011, 33(7): 973-89.
39. Neumiller, J.J., Setter, S.M. Review of linagliptin for the treatment of type 2 diabetes mellitus. Clin Ther 2012, 34(5): 993-1005.
40. Gomis, R., Espadero, R.M., Jones, R., Woerle, H.J., Dugi, K.A. Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab 2011, 13(7): 653-61.
41. Forst, T., Uhlig-Laske, B., Ring, A. et al. Linagliptin (BI 1356), a potent and selective DPP-4 inhibitor, is safe and efficacious in combination with metformin in patients with inadequately controlled Type 2 diabetes. Diabet Med 2010, 27(12): 1409-19.
42. Del Prato, S., Barnett, A.H., Huisman, H., Neubacher, D., Woerle, H.J., Dugi, K.A. Effect of linagliptin monotherapy on glycaemic control and markers of beta-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial. Diabetes Obes Metab 2011, 13(3): 258-67.
43. Owens, D.R., Swallow, R., Dugi, K.A., Woerle, H.J. Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study. Diabet Med 2011, 28(11): 1352-61.