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Clinical Focus: Diabetes

Linagliptin: A New DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus

, MD, PhD
Pages 46-53 | Published online: 13 Mar 2015

References

  • . FDA approves new treatment for type 2 diabetes. FDA news release. May 2, 2011. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm253501.htm. Accessed May 9, 2011
  • . Tradjenta [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2011. http://www.tradjenta.com/TRAD-JENTA_(TM)_(linagliptin)_tablets_Prescribing_Information_including_Patient_Information.pdf. Accessed May 3, 2011
  • . Gorrell MD, Gysbers V, McCaughan GW. CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. Scand J Immunol. 2001;54(3):249–264
  • . Lambeir AM, Durinx C, Scharpe S, De Meester I. Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci. 2003;40(3):209–294
  • . Orskov C, Holst JJ, Nielsen OV. Effect of truncated glucagon-like peptide-1 [proglucagon-(78–107) amide] on endocrine secretion from pig pancreas, antrum, and nonantral stomach. Endocrinology. 1988;123(4):2009–2013
  • . Komatsu R, Matsuyama T, Namba M,. Glucagonostatic and insulinotropic action of glucagonlike peptide I-(7–36)-amide. Diabetes. 1989;38(7):902–905
  • . Meier JJ, Nauck MA. Is the diminished incretin effect in type 2 diabetes just an epi-phenomenon of impaired beta-cell function? Diabetes. 2010;59(5):1117–1125
  • . 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-quinazoli n-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):175–182
  • . Heise T, Graefe-Mody EU, Hüttner S, Ring A, Trommeshauser D, Dugi KA. Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients. Diabetes Obes Metab. Aug 2009;11(8):786–794
  • . Reinhold D, Goihl A, Wrenger S,. Role of dipeptidyl peptidase IV (DP IV)-like enzymes in T lymphocyte activation: investigations in DP IV/CD26-knockout mice. Clin Chem Lab Med. 2009;47(3):268–274
  • . Lankas GR, Leiting B, Roy RS,. 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):2988–2994
  • . Taskinen MR, Rosenstock J, Tamminen I,. 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
  • . Del Prato S, Barnett AH, Huisman H, Neubacher D, Woerle HJ, Dugi KA. 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):258–267
  • . Gomis R, Espadero RM, Jones R, Woerle HJ, Dugi KA. 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 [published online ahead of print March 15, 2011]. Diabetes Obes Metab.
  • . Owens DR, Swallow R, Woerle HJ, Dugi KA. Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24 week randomised study. Diabet Med. In press
  • . Januvia [package insert]. Whitehouse Station, NJ: Merck and Co, Inc; 2010. http://www.januvia.com/sitagliptin/januvia/consumer/prescribing-information-for-januvia/index.jsp?WT.svl=3. Accessed January 19, 2011
  • . Sarashina A, Sesoko S, Nakashima M,. Linagliptin, a dipeptidyl peptidase-4 inhibitor in development for the treatment of type 2 diabetes mellitus: a phase I, randomized, double-blind, placebo-controlled trial of single and multiple escalating doses in healthy adult male Japanese subjects. Clin Ther. 2010;32(6):1188–1204
  • . Neumiller JJ, Campbell RK. Saxagliptin: a dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus. Am J Health Syst Pharm. 2010;67(18):1515–1525
  • . Deacon CF, Holst JJ. Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. Adv Ther. 2009;26(5):488–499
  • . Thornberry NA, Weber AE. Discovery of JANUVIA (sitagliptin), a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Curr Top Med Chem. 2007;7(6):557–568
  • . Herman GA, Bergman A, Liu F,. Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol. 2006;46(8):876–886
  • . Herman GA, Stevens C, Van Dyck K,. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther. 2005;78(6):675–688
  • . Huttner S, Graefe-Mody EU, Withopf B, Ring A, Dugi KA. Safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of BI 1356, an inhibitor of dipeptidyl peptidase 4, in healthy male volunteers. J Clin Pharmacol. 2008;48(10):1171–1178
  • . Onglyza [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2011. http://www.onglyza.com/. Accessed January 19, 2011
  • . Fuchs H, Tillement JP, Urien S, Greischel A, Roth W. Concentration-dependent plasma protein binding of the novel dipeptidyl peptidase 4 inhibitor BI 1356 due to saturable binding to its target in plasma of mice, rats and humans. J Pharm Pharmacol. 2009;61(1):55–62
  • . Retlich S, Withopf B, Greischel A, Staab A, Jaehde U, Fuchs H. Binding to dipeptidyl peptidase-4 determines the disposition of linagliptin (BI 1356)–investigations in DPP-4 deficient and wildtype rats. Biopharm Drug Dispos. 2009;30(8):422–436
  • . Blech S, Ludwig-Schwellinger E, Gräfe-Mody EU, Withopf B, Wagner K. The metabolism and disposition of the oral dipeptidyl peptidase-4 inhibitor, linagliptin, in humans. Drug Metab Dispos. 2010;38(4):667–678
  • . Graefe-Mody EU, Rose P, Ring A, Waldhauser L, Cinca R, Woerle HJ. The novel DPP-4 inhibitor linagliptin can be administered to patients with various degrees of hepatic impairment without dose adjustment. Presented at: 4th International Conference on Prediabetes and the Metabolic Syndrome; April 6–9, 2011; Madrid, Spain
  • . Graefe-Mody EU, Padula S, Ring A, Withopf B, Dugi KA. Evaluation of the potential for steady-state pharmacokinetic and pharmacodynamic interactions between the DPP-4 inhibitor linagliptin and metformin in healthy subjects. Curr Med Res Opin. 2009;25(8):1963–1972
  • . Graefe-Mody U, Rose P, Ring A, Zander K, Iovino M, Woerle HJ. 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):123–129
  • . Lewin AJ, Arvay L, Liu D. Safety and efficacy of linagliptin as add-on therapy to a sulphonylurea in inadequately controlled type 2 diabetes. Presented at: 46th Annual Meeting of European Association for the Study of Diabetes; September 20–24, 2010; Stockholm, Sweden. Poster 821-P. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2010/22_september_2010_diabetes.html. Accessed May 9, 2011
  • . Friedrich C, Ring A, Brand T, Sennewald R, Graefe-Mody EU, Woerle HJ. Evaluation of the pharmacokinetic interaction after multiple oral doses of linagliptin and digoxin in healthy volunteers. Eur J Drug Metab Pharmacokinet. 36(1):17–24
  • . Graefe-Mody U, Huettner S, Stahle H, Ring A, Dugi KA. Effect of linagliptin (BI 1356) on the steady-state pharmacokinetics of simvastatin. Int J Clin Pharmacol Ther. 2010;48(6):367–374
  • . Graefe-Mody EU, Jungnik A, Ring A, Woerle HJ, Dugi KA. Evaluation of the pharmacokinetic interaction between the dipeptidyl peptidase-4 inhibitor linagliptin and pioglitazone in healthy volunteers. Int J Clin Pharmacol Ther. 2010;48(10):652–661
  • . Gomis R, Espadero RM, Jones R, Woerle HJ, Dugi KA. Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes. Presented at: 70th Scientific Sessions of American Diabetes Association; June 25–29, 2010; Orlando, FL. Poster 551-P
  • . Ahren B. Clinical results of treating type 2 diabetic patients with sitagliptin, vildagliptin or saxagliptin–diabetes control and potential adverse events. Best Pract Res Clin Endocrinol Metab. 2009;23(4):487–498
  • . Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P; Sitagliptin Study 035 Group. 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):733–745
  • . Garber AJ, Foley JE, Banerji MA,. Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea. Diabetes Obes Metab. 2008;10(11):1047–1056
  • . Trujillo A, Rendell M, Chrysant SG,. Linagliptin improves glycemic control independent of body mass index in patients with type 2 diabetes. Presented at: 20th Annual Meeting of American Association of Clinical Endocrinologists; April 13–17, 2011; San Diego, CA
  • . Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14

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