58
Views
1
CrossRef citations to date
0
Altmetric
Drug Profile

Clinical overview of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with Type 2 diabetes mellitus

&
Pages 21-35 | Published online: 10 Jan 2014

References

  • Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with Type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 281(21), 2005–2012 (1999).
  • Després JP, Arsenault BJ, Côté M, Cartier A, Lemieux I. Abdominal obesity: the cholesterol of the 21st Century? Can. J. Cardiol. 24(Suppl. D), 7D–12D (2008).
  • DeFronzo RA. Insulin resistance, lipotoxicity, Type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia 53(7), 1270–1287 (2010).
  • Ohashi K, Ouchi N, Matsuzawa Y. Adiponectin and hypertension. Am. J. Hypertens. 24(3), 263–269 (2011).
  • Imai A, Komatsu S, Ohara T et al. Visceral abdominal fat accumulation predicts the progression of noncalcified coronary plaque. Atherosclerosis 222(2), 524–529 (2012).
  • Gastaldelli A, Sironi AM, Ciociaro D et al. Visceral fat and β cell function in non-diabetic humans. Diabetologia 48(10), 2090–2096 (2005).
  • Raz I, Eldor R, Cernea S, Shafrir E. Diabetes: insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage. Diabetes Metab. Res. Rev. 21(1), 3–14 (2005).
  • Handelsman Y, Mechanick JI, Blonde L et al.; AACE Task Force for Developing Diabetes Comprehensive Care Plan. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr. Pract. 17(Suppl. 2), 1–53 (2011).
  • Inzucchi SE, Bergenstal RM, Buse JB et al.; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in Type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35(6), 1364–1379 (2012).
  • Garber AJ. Novel incretin-based agents and practical regimens to meet needs and treatment goals of patients with Type 2 diabetes mellitus. J. Am. Osteopath. Assoc. 111(7 Suppl. 5), S20–S30 (2011).
  • American Diabetes Association. Standards of medical care in diabetes-2012. Diabetes Care 35(Suppl. 1), S11–S63 (2012).
  • Rodbard HW, Jellinger PS, Davidson JA et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on Type 2 diabetes mellitus: an algorithm for glycemic control. Endocr. Pract. 15(6), 540–559 (2009).
  • Rydén L, Standl E, Bartnik M et al.; Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC); European Association for the Study of Diabetes (EASD). Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur. Heart J. 28(1), 88–136 (2007).
  • Forst T, Pfützner A. Linagliptin, a dipeptidyl peptidase-4 inhibitor with a unique pharmacological profile, and efficacy in a broad range of patients with Type 2 diabetes. Expert Opin. Pharmacother. 13(1), 101–110 (2012).
  • Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in Type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 343, d4169 (2011).
  • Duckworth W, Abraira C, Moritz T et al. Glucose control and vascular complications in veterans with Type 2 diabetes. N. Engl. J. Med. 360(2), 129–139 (2009).
  • Gerstein HC, Miller ME, Byington RP et al.; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in Type 2 diabetes. N. Engl. J. Med. 358(24), 2545–2559 (2008).
  • Hemmingsen B, Lund SS, Gluud C et al. Intensive glycaemic control for patients with Type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ 343, d6898 (2011).
  • Patel A, MacMahon S, Chalmers J et al.; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with Type 2 diabetes. N. Engl. J. Med. 358(24), 2560–2572 (2008).
  • Rossing P, de Zeeuw D. Need for better diabetes treatment for improved renal outcome. Kidney Int. Suppl. 120, S28–S32 (2011).
  • Forst T, Hohberg C, Fuellert SD et al. Pharmacological PPARγ stimulation in contrast to β cell stimulation results in an improvement in adiponectin and proinsulin intact levels and reduces intima media thickness in patients with Type 2 diabetes. Horm. Metab. Res. 37(8), 521–527 (2005).
  • Pscherer S, Larbig M, von Stritsky B, Pfützner A, Forst T. In Type 2 diabetes patients, insulin glargine is associated with lower postprandial release of intact proinsulin compared with sulfonylurea treatment. J. Diabetes Sci. Technol. 6(3), 634–640 (2012).
  • Gallwitz B. The evolving place of incretin-based therapies in Type 2 diabetes. Pediatr. Nephrol. 25(7), 1207–1217 (2010).
  • Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in Type 2 diabetes. Lancet 368(9548), 1696–1705 (2006).
  • Barnett AH. Linagliptin: a novel dipeptidyl peptidase 4 inhibitor with a unique place in therapy. Adv. Ther. 28(6), 447–459 (2011).
  • Richard KR, Shelburne JS, Kirk JK. Tolerability of dipeptidyl peptidase-4 inhibitors: a review. Clin. Ther. 33(11), 1609–1629 (2011).
  • Del Prato S, Barnett AH, Huisman H, Neubacher D, Woerle HJ, Dugi KA. Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled Type 2 diabetes: a randomized controlled trial. Diabetes. Obes. Metab. 13(3), 258–267 (2011).
  • Kawamori R, Inagaki N, Araki E et al. Linagliptin monotherapy provides superior glycaemic control versus placebo or voglibose with comparable safety in Japanese patients with Type 2 diabetes: a randomized, placebo and active comparator-controlled, double-blind study. Diabetes. Obes. Metab. 14(4), 348–357 (2012).
  • 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 380(9840), 475–483 (2012).
  • Duez H, Cariou B, Staels B. DPP-4 inhibitors in the treatment of Type 2 diabetes. Biochem. Pharmacol. 83(7), 823–832 (2012).
  • Jose T, Inzucchi SE. Cardiovascular effects of the DPP-4 inhibitors. Diab. Vasc. Dis. Res. 9(2), 109–116 (2012).
  • Baetta R, Corsini A. Pharmacology of dipeptidyl peptidase-4 inhibitors: similarities and differences. Drugs 71(11), 1441–1467 (2011).
  • Freeman MK. Efficacy and safety of linagliptin (Tradjenta) in adults with Type-2 diabetes mellitus. P. T. 36(12), 807–842 (2011).
  • 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. 325(1), 175–182 (2008).
  • Hüttner 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. 48(10), 1171–1178 (2008).
  • 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. 11(8), 786–794 (2009).
  • 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. 61(1), 55–62 (2009).
  • Fuchs H, Binder R, Greischel A. Tissue distribution of the novel DPP-4 inhibitor BI 1356 is dominated by saturable binding to its target in rats. Biopharm. Drug Dispos. 30(5), 229–240 (2009).
  • 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. 38(4), 667–678 (2010).
  • Graefe-Mody U, Rose P, Retlich S et al. Pharmacokinetics of linagliptin in subjects with hepatic impairment. Br. J. Clin. Pharmacol. 74(1), 75–85 (2012).
  • 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. 13(10), 939–946 (2011).
  • Graefe-Mody U, Retlich S, Friedrich C. Clinical pharmacokinetics and pharmacodynamics of linagliptin. Clin. Pharmacokinet. 51(7), 411–427 (2012).
  • 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. 25(8), 1963–1972 (2009).
  • 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. 48(10), 652–661 (2010).
  • 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. 26(2), 123–129 (2011).
  • Graefe-Mody U, Huettner S, Stähle H, Ring A, Dugi KA. Effect of linagliptin (BI 1356) on the steady-state pharmacokinetics of simvastatin. Int. J. Clin. Pharmacol. Ther. 48(6), 367–374 (2010).
  • Graefe-Mody EU, Brand T, Ring A et al. Effect of linagliptin on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. Int. J. Clin. Pharmacol. Ther. 49(5), 300–310 (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 (2011).
  • Friedrich C, Port A, Ring A et al. 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. 31(9), 643–653 (2011).
  • 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. 27(12), 1409–1419 (2010).
  • Forst T, Uhlig-Laske B, Ring A, Ritzhaupt A, Graefe-Mody U, Dugi KA. The oral DPP-4 inhibitor linagliptin significantly lowers HbA1c after 4 weeks of treatment in patients with Type 2 diabetes mellitus. Diabetes. Obes. Metab. 13(6), 542–550 (2011).
  • 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. 33(7), 973–989 (2011).
  • Rauch T, Graefe-Mody U, Deacon CF et al. Linagliptin increases incretin levels, lowers glucagon, and improves glycemic control in Type 2 diabetes mellitus. Diabetes Ther. 3(1), 10 (2012).
  • Barnett AH, Patel S, Harper R et al. Linagliptin monotherapy in Type 2 diabetes patients for whom metformin is inappropriate: an 18-week randomized, double-blind, placebo-controlled Phase III trial with a 34-week active-controlled extension. Diabetes. Obes. Metab. 14(12), 1145–1154 (2012).
  • Taskinen MR, Rosenstock J, Tamminen I et al. 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. 13(1), 65–74 (2011).
  • Lewin AJ, Arvay L, Liu D, Patel S, von Eynatten M, Woerle HJ. Efficacy and tolerability of linagliptin added to a sulfonylurea regimen in patients with inadequately controlled Type 2 diabetes mellitus: an 18-week, multicenter, randomized, double-blind, placebo-controlled trial. Clin. Ther. 34(9), 1909–1919.e15 (2012).
  • Owens DR, Swallow R, Dugi KA, Woerle HJ. 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. 28(11), 1352–1361 (2011).
  • 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. Diabetes. Obes. Metab. 13(7), 653–661 (2011).
  • Haak T, Meinicke T, Jones R, Weber S, von Eynatten M, Woerle HJ. Initial combination of linagliptin and metformin improves glycaemic control in Type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes. Obes. Metab. 14(6), 565–574 (2012).
  • McGill JB, Sloan L, Newman J et al. Long-term efficacy and safety of linagliptin in patients with Type 2 diabetes and severe renal impairment: a 1-year, randomized, double-blind, placebo-controlled study. Diabetes Care doi:10.2337/dc12-0706 (2012) (Epub ahead of print).
  • Schernthaner G, Barnett AH, Emser A et al. Safety and tolerability of linagliptin: a pooled analysis of data from randomized controlled trials in 3572 patients with Type 2 diabetes mellitus. Diabetes. Obes. Metab. 14(5), 470–478 (2012).
  • Holst J, de Heer J. Sulfonylurea compounds uncouple the glucose-dependence of the insulinotropic effect of glucagon-like peptide-1. Diabetes 56(2), 438–443 (2007).
  • Johansen OE, Neubacher D, von Eynatten M, Patel S, Woerle HJ. Cardiovascular safety with linagliptin in patients with Type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a Phase 3 programme. Cardiovasc. Diabetol. 11, 3 (2012).
  • Ross SA, Rafeiro E, Meinicke T, Toorawa R, Weber-Born S, Woerle HJ. Efficacy and safety of linagliptin 2.5 mg twice daily versus 5 mg once daily in patients with Type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, placebo-controlled trial. Curr. Med. Res. Opin. 28(9), 1465–1474 (2012).
  • Russell-Jones D, Cuddihy RM, Hanefeld M et al.; DURATION-4 Study Group. Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with Type 2 diabetes (DURATION-4): a 26-week double-blind study. Diabetes Care 35(2), 252–258 (2012).
  • Bergenstal RM, Wysham C, Macconell L et al.; DURATION-2 Study Group. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of Type 2 diabetes (DURATION-2): a randomised trial. Lancet 376(9739), 431–439 (2010).
  • Pratley RE, Nauck M, Bailey T et al.; 1860-LIRA-DPP-4 Study Group. Liraglutide versus sitagliptin for patients with Type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet 375(9724), 1447–1456 (2010).
  • Andukuri R, Drincic A, Rendell M. Alogliptin: a new addition to the class of DPP-4 inhibitors. Diabetes. Metab. Syndr. Obes. 2, 117–126 (2009).
  • Rosenstock J. Clinical overview of saxagliptin for Type 2 diabetes management. Expert Rev. Endocrinol. Metab. 5(6), 809–823 (2010).
  • He YL. Clinical pharmacokinetics and pharmacodynamics of vildagliptin. Clin. Pharmacokinet. 51(3), 147–162 (2012).

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.