title: Rhinorrhea, cough and fatigue in patients taking sitagliptin.
abstract: Sitagliptin is a dipeptidyl peptidase-4 (DPP IV, CD26) inhibitor indicated for treatment of Type II diabetes as a second line therapy after metformin. We report fifteen sitagliptin intolerant patients who developed anterior and posterior rhinorrhea, cough, dyspnea, and fatigue. Symptoms typically developed within 1 to 8 weeks of starting, and resolved within 1 week of stopping the drug. Peak expiratory flow rates increased 34% in 8 patients who stopped sitagliptin. Similar changes were found in 4 out of 5 persons who had confirmatory readministration. Chart review identified 17 patients who tolerated sitagliptin and had no symptomatic changes. The sitagliptin intolerant group had higher rates of clinically diagnosed allergic rhinitis (15/15 vs. 6/18; p = 0.00005), Fisher's Exact test) and angiotensin converting enzyme inhibitor - induced cough (6/13 vs. 1/18; p = 0.012). Nasal and inhaled glucocorticoids may control the underlying allergic inflammation and abrogate this new sitagliptin - induced pharmacological syndrome. Potential mucosal and central nervous system mechanisms include disruption of neuropeptides and/or cytokines that rely on DPP IV for activation or inactivation, and T cell dysfunction.
authors.affiliation: Department of Family Medicine, Quillen College of Medicine, East Tennessee State University, McMinnville, TN, USA. drmjamieson@gmail.com.
authors.forename: James N
authors.initials: JN
authors.lastname: Baraniuk
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Jamieson
references.citation: Best Pract Res Clin Endocrinol Metab. 2009 Aug;23(4):487-98
references.pmid: 19748066
references.citation: J Rheumatol. 2002 Sep;29(9):1858-66
references.pmid: 12233879
references.citation: Curr Allergy Asthma Rep. 2009 Mar;9(2):149-52
references.pmid: 19210905
references.citation: J Allergy Clin Immunol. 2008 Feb;121(2 Suppl):S398-401; quiz S419
references.pmid: 18241690
references.citation: Am J Respir Cell Mol Biol. 1994 Aug;11(2):173-80
references.pmid: 8049077
references.citation: Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006739
references.pmid: 18425967
references.citation: Ann Intern Med. 1992 Aug 1;117(3):234-42
references.pmid: 1616218
references.citation: Biochemistry. 2003 Jan 28;42(3):694-701
references.pmid: 12534281
references.citation: BMJ. 2009 May 22;338:b1668
references.pmid: 19465464
references.citation: Hypertension. 2010 Feb;55(2):214-20
references.pmid: 20065150
references.citation: Chest. 2006 Jan;129(1 Suppl):169S-173S
references.pmid: 16428706
references.citation: Cardiol Rev. 2007 Nov-Dec;15(6):316-23
references.pmid: 18090068
references.citation: Eur Respir J. 2008 Jan;31(1):143-78
references.pmid: 18166595
references.citation: J Clin Epidemiol. 2007 Jun;60(6):547-53
references.pmid: 17493508
references.citation: J Allergy Clin Immunol. 2007 Aug;120(2):403-8
references.pmid: 17531305
references.citation: Adv Exp Med Biol. 2006;575:223-9
references.pmid: 16700526
references.citation: Curr Allergy Asthma Rep. 2007 May;7(2):100-4
references.pmid: 17437679
references.citation: J Clin Immunol. 2007 Jul;27(4):430-7
references.pmid: 17525828
references.citation: J Appl Physiol (1985). 1992 Nov;73(5):1867-72
references.pmid: 1282125
references.citation: Am J Respir Crit Care Med. 2005 Jan 1;171(1):5-11
references.pmid: 15477496
references.citation: Int Immunol. 1999 Mar;11(3):417-26
references.pmid: 10221653
references.citation: Handb Exp Pharmacol. 2009;(187):241-62
references.pmid: 18825344
references.citation: Respir Physiol Neurobiol. 2006 Jul 28;152(3):340-8
references.pmid: 16326149
references.citation: Peptides. 2004 Mar;25(3):521-5
references.pmid: 15134871
references.citation: Curr Top Med Chem. 2007;7(6):621-35
references.pmid: 17352682
references.citation: Clin Exp Rheumatol. 2001 Nov-Dec;19(6):673-80
references.pmid: 11791639
references.citation: Diabetologia. 2005 Apr;48(4):616-20
references.pmid: 15770466
references.citation: J Appl Physiol (1985). 1992 Nov;73(5):2069-73
references.pmid: 1474087
references.citation: Vasc Health Risk Manag. 2008;4(4):753-68
references.pmid: 19065993
references.citation: J Immunol. 2001 Dec 15;167(12):6745-55
references.pmid: 11739489
references.citation: Eur Arch Psychiatry Clin Neurosci. 2000;250(2):86-92
references.pmid: 10853924
references.citation: Am J Respir Cell Mol Biol. 1993 Nov;9(5):557-67
references.pmid: 8217197
references.citation: Clin Allergy Immunol. 2007;19:35-53
references.pmid: 17153006
references.citation: Biol Chem. 2002 Jul-Aug;383(7-8):1133-8
references.pmid: 12437097
references.citation: Bioorg Med Chem. 2003 Jan 17;11(2):207-15
references.pmid: 12470715
references.citation: Prim Care Respir J. 2009 Dec;18(4):250-7
references.pmid: 19513495
references.citation: Respiration. 2008;75(1):89-97
references.pmid: 17637510
references.citation: J Hum Hypertens. 2005 Oct;19(10):793-9
references.pmid: 15951740
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1996 Nov;354(5):662-9
references.pmid: 8938667
references.citation: Regul Pept. 2002 Jun 15;106(1-3):71-9
references.pmid: 12047913
references.citation: Schweiz Med Wochenschr. 2000;Suppl 125:99S-101S
references.pmid: 11141955
references.citation: Science. 2007 Sep 28;317(5846):1881-6
references.pmid: 17901324
references.citation: Eur Arch Otorhinolaryngol. 1995;252(8):465-8
references.pmid: 8719587
references.citation: Horm Metab Res. 2008 Dec;40(12):892-5
references.pmid: 18726829
references.citation: J Allergy Clin Immunol. 2009 Sep;124(3):447-53
references.pmid: 19647861
references.citation: Eur Arch Otorhinolaryngol. 1995;252(2):83-5
references.pmid: 7541210
references.citation: FASEB J. 2002 Jul;16(9):1132-4
references.pmid: 12039843