Safety and tolerability of sitagliptin in clinical studies: A pooled analysis of data from 10,246 patients with type 2 diabetes

BMC Endocrine Disorders

Volumn 10, Issue , 2010, Pages

  Williams Herman, Debora ^a   Engel, Samuel S ^a   Round, Elizabeth ^a   Johnson, Jeremy ^a   Golm, Gregory T ^a   Guo, Hua ^a   Musser, Bret J ^a   Davies, Michael J ^a   Kaufman, Keith D ^a   Goldstein, Barry J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLIMEPIRIDE; GLIPIZIDE; INSULIN; METFORMIN; METFORMIN PLUS SITAGLIPTIN; PIOGLITAZONE; PLACEBO; ROSIGLITAZONE; SITAGLIPTIN; SULFONYLUREA;

ABDOMINAL DISCOMFORT; ABDOMINAL DISTENSION; ABSCESS; ACNE; ACUTE HEART INFARCTION; ADD ON THERAPY; ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALBUMINURIA; ANEMIA; ANGINA PECTORIS; ANGIONEUROTIC EDEMA; ANXIETY DISORDER; ARTHRALGIA; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BACKACHE; BASAL CELL CARCINOMA; BREAST CANCER; BRONCHITIS; CELLULITIS; CEREBROVASCULAR ACCIDENT; CLINICAL STUDY; CLINICAL TRIAL; CONSTIPATION; CONTACT DERMATITIS; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CONTUSION; CORONARY ARTERY DISEASE; COUGHING; CREATINE KINASE BLOOD LEVEL; CREATININE CLEARANCE; DECREASED APPETITE; DEPRESSION; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; EPIGASTRIC DISCOMFORT; ERYTHEMA MULTIFORME; ESCHERICHIA; ESCHERICHIA COLI INFECTION; FACE FRACTURE; FATIGUE; FEMALE; FLATULENCE; FRACTURE; GASTRITIS; GASTROENTERITIS; GASTROESOPHAGEAL REFLUX; GENITAL HERPES; GLUCOSE BLOOD LEVEL; HEADACHE; HEART ATRIUM FIBRILLATION; HEART ATRIUM FLUTTER; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HERPES SIMPLEX; HERPES ZOSTER; HERPES ZOSTER OPHTHALMICUS; HUMAN; HYPERGLYCEMIA; HYPERTENSION; HYPESTHESIA; HYPOGLYCEMIA; INFLUENZA; INSOMNIA; IRON DEFICIENCY ANEMIA; LEUKOCYTOCLASTIC VASCULITIS; LIMB PAIN; LIPOMA; LOWER ABDOMINAL PAIN; MAJOR CLINICAL STUDY; MALE; MICROALBUMINURIA; MONOTHERAPY; MULTICENTER STUDY; MUSCLE SPASM; MUSCLE STRAIN; MYALGIA; MYCOSIS; NAUSEA; NECK PAIN; NON INSULIN DEPENDENT DIABETES MELLITUS; NONCARDIAC CHEST PAIN; OPPORTUNISTIC INFECTION; OSTEOARTHRITIS; PANCREATITIS; PARESTHESIA; PERIPHERAL EDEMA; PHARYNGITIS; PNEUMONIA; PROSTATE CANCER; PROTEINURIA; PRURITUS; PYELONEPHRITIS; RANDOMIZED CONTROLLED TRIAL; RASH; RHINOPHARYNGITIS; SIDE EFFECT; SINUS HEADACHE; SINUSITIS; SKIN CANCER; SKULL FRACTURE; SORE THROAT; STAPHYLOCOCCAL BACTEREMIA; STEVENS JOHNSON SYNDROME; TOOTH PAIN; TRANSIENT ISCHEMIC ATTACK; TREATMENT DURATION; TRIACYLGLYCEROL BLOOD LEVEL; UPPER ABDOMINAL PAIN; UPPER RESPIRATORY TRACT INFECTION; URIC ACID BLOOD LEVEL; URINARY TRACT INFECTION; UTERUS MYOMA; VIRAL GASTROENTERITIS; VIRAL UPPER RESPIRATORY TRACT INFECTION; VIRUS INFECTION; VOMITING; WEIGHT GAIN; WEIGHT REDUCTION; XEROSTOMIA;

EID: 77951069227     PISSN: None     EISSN: 14726823     Source Type: Journal    
DOI: 10.1186/1472-6823-10-7     Document Type: Article

References (59)

1. Williams-Herman D, Round E, Swern AS, Musser B, Davies MJ, Stein PP, et al. Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis. BMC Endocr Disord 2008, 8:14. 10.1186/1472-6823-8-14, 2605739, 18954434.
2. McGuire DK, Inzucchi SE. New drugs for the treatment of diabetes mellitus: part I: Thiazolidinediones and their evolving cardiovascular implications. Circulation 2008, 117:440-449. 10.1161/CIRCULATIONAHA.107.704080, 18212301.
3. Smith U, Gale EA. Does diabetes therapy influence the risk of cancer?. Diabetologia 2009, 52:1699-1708. 10.1007/s00125-009-1441-5, 19597799.
4. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002, 287:360-372. 10.1001/jama.287.3.360, 11790216.
5. Inzucchi SE, McGuire DK. New drugs for the treatment of diabetes: part II: Incretin-based therapy and beyond. Circulation 2008, 117:574-584. 10.1161/CIRCULATIONAHA.107.735795, 18227398.
6. Dormuth CR, Carney G, Carleton B, Bassett K, Wright JM. Thiazolidinediones and fractures in men and women. Arch Intern Med 2009, 169:1395-1402. 10.1001/archinternmed.2009.214, 19667303.
7. Meier C, Kraenzlin ME, Bodmer M, Jick SS, Jick H, Meier CR. Use of thiazolidinediones and fracture risk. Arch Intern Med 2008, 168:820-825. 10.1001/archinte.168.8.820, 18443256.
8. Brown NJ, Byiers S, Carr D, Maldonado M, Warner BA. Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitor-associated angioedema. Hypertension 2009, 54:516-523. 10.1161/HYPERTENSIONAHA.109.134197, 19581505.
9. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA 2007, 298:194-206. 10.1001/jama.298.2.194, 17622601.
10. Monami M, Iacomelli I, Marchionni N, Mannucci E. Dipeptydil peptidase-4 inhibitors in type 2 diabetes: A meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis 2009,
11. Scott R, Wu M, Sanchez M, Stein P. Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes. Int J Clin Pract 2007, 61:171-180. 10.1111/j.1742-1241.2006.01246.x, 17156104.
12. Hanefeld M, Herman GA, Wu M, Mickel C, Sanchez M, Stein PP. Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of patients with type 2 diabetes. Curr Med Res Opin 2007, 23:1329-1339. 10.1185/030079907X188152, 17559733.
13. Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care 2007, 30:1979-1987. 10.2337/dc07-0627, 17485570.
14. Reasner CA, Olansky L, Seck T, Williams-Herman D, Luo E, Chen M, et al. Initial therapy with the fixed-dose combination (FDC) if sitagliptin and metformin (JANUMET) in patients with type 2 diabetes mellitus provides superior glycaemic control and HbA1c goal attainment with lower rates of abdominal pain and diarrhea vs metformin alone (abstract). Diabetologia 2009, 52(Suppl 1):S295.
15. Olansky L, Reasner CA, Seck T, Williams-Herman D, Luo E, Chen M, et al. A strategy implementing initial therapy with a fixed-dose combination tablet of sitagliptin and metformin in patients with type 2 diabetes provides superior glycemic control compared with a strategy using initial metformin monotherapy over 44 weeks (abstract). IDF Abstract Book 2009, 0-0535:178.
16. Chan JC, Scott R, Arjona Ferreira JC, Sheng D, Gonzalez E, Davies MJ, et al. Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency. Diabetes Obes Metab 2008, 10:545-555. 10.1111/j.1463-1326.2008.00914.x, 18518892.
17. Guidance for Industry: Collection of race and ethnicity data in clinical trials. 9/2/2005. (last accessed February 9, 2010).., http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati on/Guidances/ucm071596.pdf
18. Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med 1985, 4:213-226. 10.1002/sim.4780040211, 4023479.
19. Engel SS, Williams-Herman DE, Golm GT, Clay RJ, Machotka SV, Kaufman KD, et al. Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis. Int J Clin Pract
20. Breslow NE, Day NE. Statistical methods in cancer research. Volume II--The design and analysis of cohort studies. IARC Sci Publ 1987, 1-406.
21. Robins J, Breslow N, Greenland S. Estimators of the Mantel-Haenszel variance consistent in both sparse data and large-strata limiting models. Biometrics 1986, 42:311-323. 10.2307/2531052, 3741973.
22. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007, 11:R31. 10.1186/cc5713, 2206446, 17331245.
23. Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab 2007, 9:194-205. 10.1111/j.1463-1326.2006.00704.x, 17300595.
24. Seck T, Nauck MA, Sheng D, Sunga S, Davies MJ, Stein PP, et al. Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: A 2-year study. Int J Clin Pract 2010, 64:562-576.
25. Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P. 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, 9:733-745. 10.1111/j.1463-1326.2007.00744.x, 17593236.
26. Vilsboll T, Rosenstock J, Yki-Jarvinen H, Cefalu WT, Chen Y, Luo E, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab 2010, 12:167-177. 10.1111/j.1463-1326.2009.01173.x, 20092585.
27. Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP. Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin 2008, 24:489-496. 10.1185/030079908X261069, 18182122.
28. Alba M, Ahren B, Inzucchi SE, Guan Y, Mallick M, Xu L, et al. Initial combination therapy with sitagliptin and pioglitazone: complementary effects on postprandial glucose and islet cell function (abstract). IDF Abstract Book 2009, P-1740:584.
29. Yoon KH, Shockey GR, Teng R, Golm GT, Thakkar PR, Meehan AG, et al. Sitagliptin and pioglitazone initial combination therapy in patients with type 2 diabetes provides substantial and durable incremental improvement in glycemic control over one year compared with initial treatment with pioglitazone monotherapy (abstract). IDF Abstract Book 2009, P-1153:391.
30. Lovshin JA, Drucker DJ. Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol 2009, 5:262-269. 10.1038/nrendo.2009.48, 19444259.
31. Vella A, Bock G, Giesler PD, Burton DB, Serra DB, Saylan ML, et al. Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes. Diabetes 2007, 56:1475-1480. 10.2337/db07-0136, 17303799.
32. Stevens JE, Maddox AF, Wolthers T, Deacon C, Nauck M, Rayner CK, et al. Sitagliptin has no effect on gastric emptying in healthy humans (abstract). Australian Diabetes Society 2009, abstract # 95..
33. Hellstrom PM. GLP-1: broadening the incretin concept to involve gut motility. Regul Pept 2009, 156:9-12. 10.1016/j.regpep.2009.04.004, 19362109.
34. Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch CL. Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev 2008, CD006739.
35. Kimmel D, Cusick T, Mu J, Pennypacker B, Shen XL, Li ZH, et al. Thiazolidinediones, but not sitagliptin, exacerbate ovariectomy-induced bone loss in rats (abstract). Diabetes 2009, 58(Suppl 1):A374.
36. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998, 339:229-234. 10.1056/NEJM199807233390404, 9673301.
37. The University Group Diabetes Program A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. Mortality results. Diabetes 1970, 19(Suppl 1):789-830. The University Group Diabetes Program.
38. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007, 356:2457-2471. 10.1056/NEJMoa072761, 17517853.
39. Bethel MA, Green J, Califf RM, Holman RR. Rationale and design of the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) (abstract). Diabetologia 2009, 52(Suppl 1):S480.
40. Giovannucci E, Michaud D. The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology 2007, 132:2208-2225. 10.1053/j.gastro.2007.03.050, 17498513.
41. Okolo S. Incidence, aetiology and epidemiology of uterine fibroids. Best Pract Res Clin Obstet Gynaecol 2008, 22:571-588. 10.1016/j.bpobgyn.2008.04.002, 18534913.
42. Pandya KA, Radke F. Benign skin lesions: lipomas, epidermal inclusion cysts, muscle and nerve biopsies. Surg Clin North Am 2009, 89:677-687. 10.1016/j.suc.2009.03.002, 19465204.
43. European Medicines Agency (EMEA): Galvus (vildagliptin) - European Public Assessment Report (EPAR) - Scientific Discussion. 2007, (last accessed February 9, 2010).., http://www.emea.europa.eu/humandocs/PDFs/EPAR/galvus/H-771-en6.pdf
44. European Medicines Agency (EMEA): Onglyza (saxagliptin) - European Public Assessment Report (EPAR) - CHMP Assessment Report. 2009, (last accessed February 9, 2010).., http://www.emea.europa.eu/humandocs/PDFs/EPAR/onglyza/H-1039-en6.pdf
45. European Medicines Agency (EMEA): Januvia (sitagliptin) - European Public Assessment Report (EPAR) - Scientific Discussion. 2007, (last accessed February 9, 2010).., http://www.emea.europa.eu/humandocs/PDFs/EPAR/januvia/H-722-en6.pdf
46. Byrd JB, Shreevatsa A, Putlur P, Foretia D, McAlexander L, Sinha T, et al. Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema. J Allergy Clin Immunol 2007, 120:403-408. 10.1016/j.jaci.2007.04.012, 17531305.
47. Byrd JB, Touzin K, Sile S, Gainer JV, Yu C, Nadeau J, et al. Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema. Hypertension 2008, 51:141-147. 10.1161/HYPERTENSIONAHA.107.096552, 2749928, 18025295.
48. Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther 2006, 28:1556-1568. 10.1016/j.clinthera.2006.10.007, 17157112.
49. Charbonnel B, Karasik A, Liu J, Wu M, Meininger G. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care 2006, 29:2638-2643. 10.2337/dc06-0706, 17130197.
50. Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 2006, 29:2632-2637. 10.2337/dc06-0703, 17130196.
51. Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2006, 49:2564-2571. 10.1007/s00125-006-0416-z, 17001471.
52. Williams-Herman D, Johnson J, Teng R, Luo E, Davies MJ, Kaufman KD, et al. Efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes: a 54-week study. Curr Med Res Opin 2009, 25:569-583. 10.1185/03007990802705679, 19232032.
53. Williams-Herman D, Johnson J, Teng R, Golm G, Kaufman KD, Goldstein BJ, et al. Efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy over 2 years in patients with type 2 diabetes. Diabetes Obes Metab 2010, 12:442-451. 10.1111/j.1463-1326.2010.01204.x, 20415693.
54. Mohan V, Yang W, Son HY, Xu L, Noble L, Langdon RB, et al. Efficacy and safety of sitagliptin in the treatment of patients with type 2 diabetes in China, India, and Korea. Diabetes Res Clin Pract 2009, 83:106-116. 10.1016/j.diabres.2008.10.009, 19097665.
55. Barzilai N, Mahoney EM, Guo H, Golm GT, Williams-Herman D, Kaufman KD, et al. Sitagliptin monotherapy is an effective and well-tolerated treatment for type 2 diabetes in elderly patients (abstract). 61st Annual Scientific Meeting of the Gerontological Society of America 2008,
56. Aschner P, Katzeff H, Guo H, Sunga S, Williams-Herman D, Kaufman KD, et al. Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes. Diabetes Obes Metab 2010, 12:252-261. 10.1111/j.1463-1326.2009.01187.x, 20070351.
57. Dobs A, Goldstein BJ, Wieczorek L, Golm G, Davies MJ, Williams-Herman D, et al. Triple combination therapy with sitagliptin, metformin, and rosiglitazone improves glycemic control in patients with type 2 diabetes (abstract). Diabetes 2008, 57(Suppl 1):A595-A596.
58. Raz I, Chen Y, Wu M, Hussain S, Kaufman KD, Amatruda JM, et al. Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes. Curr Med Res Opin 2008, 24:537-550. 10.1185/030079908X260925, 18194595.
59. Scott R, Loeys T, Davies MJ, Engel SS. Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes. Diabetes Obes Metab 2008, 10:959-969. 10.1111/j.1463-1326.2007.00839.x, 18201203.