• 1
    US Food and Drug Administration. FDA approves new treatment for type 2 diabetes. May 2, 2011. Available at (last accessed 19 March 2012).
  • 2
    Boehringer Ingelheim Pharmaceuticals, Inc. Tradjenta (Linagliptin) Package Insert. Ridgefield, CT; 2011. Tradjenta [Package Insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc, 2011; Available at (last accessed 3 May 2011).
  • 3
    Blech S, Ludwig-Schwellinger E, Grafe-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: 667678.
  • 4
    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: 175182.
  • 5
    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: 5562.
  • 6
    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: 11711178.
  • 7
    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: 422436.
  • 8
    Retlich S, Duval V, Ring A, Staab A, Huttner S, Jungnik A, Jaehde U, Dugi KA, Graefe-Mody U. Pharmacokinetics and pharmacodynamics of single rising intravenous doses (0.5 mg–10 mg) and determination of absolute bioavailability of the dipeptidyl peptidase-4 inhibitor linagliptin (BI 1356) in healthy male subjects. Clin Pharmacokinet 2010; 49: 829840.
  • 9
    Cheung BM, Ong KL, Cherny SS, Sham PC, Tso AW, Lam KS. Diabetes prevalence and therapeutic target achievement in the United States, 1999 to 2006. Am J Med 2009; 122: 443453. Pharmacokinetics Of Single And Multiple Oral Doses Of 5 mg Linagliptin In Healthy Chinese Volunteers. Presented at the 2011 annual meeting of the American Association of Clinical Pharmacology, September 11–13, Chicago, IL.
  • 10
    Cotton P. Examples abound of gaps in medical knowledge because of groups excluded from scientific study. JAMA 1990; 263: 10511055.
  • 11
    Evelyn B, Toigo T, Banks D, Pohl D, Gray K, Robins B, Ernat J. Participation of racial/ethnic groups in clinical trials and race-related labeling: a review of new molecular entities approved 1995–1999. J Natl Med Assoc 2001; 93: 18S24S.
  • 12
    Shaya FT, Gbarayor CM, Huiwen Keri Y, Agyeman-Duah M, Saunders E. A perspective on African American participation in clinical trials. Contemp Clin Trials 2007; 28: 213217.
  • 13
    Svensson CK. Representation of American blacks in clinical trials of new drugs. JAMA 1989; 261: 263265.
  • 14
    Goran MI. Ethnic-specific pathways to obesity-related disease: the Hispanic vs. African-American paradox. Obesity (Silver Spring) 2008; 16: 25612565.
  • 15
    Haffner SM, D'Agostino R, Saad MF, Rewers M, Mykkanen L, Selby J, Howard G, Savage PJ, Hamman RF, Wagenknecht LE, Bergman RN. Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study. Diabetes 1996; 45: 742748.
  • 16
    Haffner SM, Howard G, Mayer E, Bergman RN, Savage PJ, Rewers M, Mykkanen L, Karter AJ, Hamman R, Saad MF. Insulin sensitivity and acute insulin response in African-Americans, non-Hispanic whites, and Hispanics with NIDDM: the Insulin Resistance Atherosclerosis Study. Diabetes 1997; 46: 6369.
  • 17
    Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Roger VL, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J. Heart disease and stroke statistics–2010 update: a report from the American Heart Association. Circulation 2010; 121: e46e215.
  • 18
    Marshall MC Jr. Diabetes in African Americans. Postgrad Med J 2005; 81: 734740.
  • 19
    Orsi JM, Margellos-Anast H, Whitman S. Black-white health disparities in the United States and Chicago: a 15-year progress analysis. Am J Public Health 2010; 100: 349356.
  • 20
    Xu J, Kochanek K, Murphy S, Tejada-Vera B. Deaths: Final Data for 2007. Hyattsville, MD: National Center for Health Statistics, 2010.
  • 21
    Cavaco I, Reis R, Gil JP, Ribeiro V. CYP3A4*1B and NAT2*14 alleles in a native African population. Clin Chem Lab Med 2003; 41: 606609.
  • 22
    Schirmer M, Toliat MR, Haberl M, Suk A, Kamdem LK, Klein K, Brockmoller J, Nurnberg P, Zanger UM, Wojnowski L. Genetic signature consistent with selection against the CYP3A4*1B allele in non-African populations. Pharmacogenet Genomics 2006; 16: 5971.
  • 23
    Scott SA, Khasawneh R, Peter I, Kornreich R, Desnick RJ. Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups. Pharmacogenomics 2010; 11: 781791.
  • 24
    Walker AH, Jaffe JM, Gunasegaram S, Cummings SA, Huang CS, Chern HD, Olopade OI, Weber BL, Rebbeck TR. Characterization of an allelic variant in the nifedipine-specific element of CYP3A4: ethnic distribution and implications for prostate cancer risk. Mutations in brief no. 191. Online. Hum Mutat 1998; 12: 289.
  • 25
    Ameyaw MM, Regateiro F, Li T, Liu X, Tariq M, Mobarek A, Thornton N, Folayan GO, Githang'a J, Indalo A, Ofori-Adjei D, Price-Evans DA, McLeod HL. MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics 2001; 11: 217221.
  • 26
    Brinkmann U, Eichelbaum M. Polymorphisms in the ABC drug transporter gene MDR1. Pharmacogenomics J 2001; 1: 5964.
  • 27
    Hashida T, Masuda S, Uemoto S, Saito H, Tanaka K, Inui K. Pharmacokinetic and prognostic significance of intestinal MDR1 expression in recipients of living-donor liver transplantation. Clin Pharmacol Ther 2001; 69: 308316.
  • 28
    Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A 2000; 97: 34733478.
  • 29
    Kurata Y, Ieiri I, Kimura M, Morita T, Irie S, Urae A, Ohdo S, Ohtani H, Sawada Y, Higuchi S, Otsubo K. Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Clin Pharmacol Ther 2002; 72: 209219.
  • 30
    Lown KS, Mayo RR, Leichtman AB, Hsiao HL, Turgeon DK, Schmiedlin-Ren P, Brown MB, Guo W, Rossi SJ, Benet LZ, Watkins PB. Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin Pharmacol Ther 1997; 62: 248260.
  • 31
    Schaeffeler E, Eichelbaum M, Brinkmann U, Penger A, Asante-Poku S, Zanger UM, Schwab M. Frequency of C3435T polymorphism of MDR1 gene in African people. Lancet 2001; 358: 383384.
  • 32
    Friedrich C, Glund S, Lionetti D, Kissling CJ, Righetti J, Patel S. Pharmacokinetic and pharmacodynamic evaluation of linagliptin in African American patients with type 2 diabetes. Presented at the 2011 Annual Meeting of the American Association of Clinical Pharmacology, September 11–13, Chicago, IL. 2011.
  • 33
    Heise T, Graefe-Mody EU, Huttner 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 2009; 11: 786794.
  • 34
    Sarashina A, Sesoko S, Nakashima M, Hayashi N, Taniguchi A, Horie Y, Graefe-Mody EU, Woerle HJ, Dugi KA. 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: 11881204.
  • 35
    Friedrich C, Shi X, Zeng P, Ring A, Woerle HJ, Patel S. Pharmacokinetics of single and multiple oral doses of 5 mg linagliptin in healthy Chinese volunteers. Int J Clin Pharmacol Ther 2012; 50: 889895.
  • 36
    Horie Y, Kanada S, Watada H, Sarashina A, Taniguchi A, Hayashi N, Graefe-Mody EU, Woerle HJ, Dugi KA. 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: 973989.