A randomized clinical trial evaluating the safety and efficacy of sitagliptin added to the combination of sulfonylurea and metformin in patients with type 2 diabetes mellitus and inadequate glycemic control

Journal of Diabetes

Volumn 8, Issue 5, 2016, Pages 701-711

  Moses, Robert G ^a   Round, Elizabeth ^b   Shentu, Yue ^b   Golm, Gregory T ^b   O'neill, Edward A ^b   Gantz, Ira ^b   Engel, Samuel S ^b   Kaufman, Keith D ^b   Goldstein, Barry J ^b,c  

^a Illawarra Shoalhaven Local Health District   (Australia)

^b MERCK RESEARCH LABORATORIES   (United States)

^c Late Stage Developmental Services Covance Inc   (United States)

Author keywords

combination therapy; dipeptidyl peptidase 4; incretins

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; GLICLAZIDE; GLIMEPIRIDE; GLUCOSE; HEMOGLOBIN A1C; METFORMIN; PIOGLITAZONE; PLACEBO; SITAGLIPTIN;

ADD ON THERAPY; ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ASIAN; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BILIRUBIN BLOOD LEVEL; CAUCASIAN; CLINICAL EFFECTIVENESS; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; EDEMA; FEMALE; GENERALIZED EDEMA; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HUMAN; HYPOGLYCEMIA; INCIDENCE; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; OPEN STUDY; PERIPHERAL EDEMA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; WEIGHT GAIN;

EID: 84983036383     PISSN: 17530393     EISSN: 17530407     Source Type: Journal    
DOI: 10.1111/1753-0407.12351     Document Type: Article

References (38)

1. Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res.Clin.Pract. 2011; 94: 311–21.
2. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N. Engl. J. Med. 1993; 329: 977–86.
3. Stratton IM, Adler AI, Neil HA et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ 2000; 321: 405–12.
4. Goldstein BJ, Gomis R, Lee HK, Leiter LA. Type 2 diabetes: Treat early, treat intensively. Int.J.Clin.Pract. 2007; 61: (Suppl. s157):16–21.
5. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: Scientific review. JAMA 2002; 287: 360–72.
6. Panten U, Schwanstecher M, Schwanstecher C. Sulfonylurea receptors and mechanism of sulfonylurea action. Exp.Clin.Endocrinol.Diabetes. 1996; 104: 1–9.
7. Hundal RS, Krssak M, Dufour S, et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes. 2000; 49: 2063–9.
8. Inzucchi SE, Maggs DG, Spollett GR, et al. Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N.Engl.J.Med. 1998; 338: 867–72.
9. 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: 557–68.
10. Bergman AJ, Stevens C, Zhou Y, et al. Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: A double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin.Ther. 2006; 28: 55–72.
11. Herman GA, Bergman A, Stevens C, et al. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J. Clin. Endocrinol. Metabol. 2006; 91: 4612–9.
12. Brazg R, Xu L, Dalla MC, Cobelli C, Thomas K, Stein PP: Effect of adding sitagliptin, a dipeptidyl peptidase-4 inhibitor, to metformin on 24-h glycaemic control and beta-cell function in patients with type 2 diabetes. Diabetes Obes.Metab 2007; 9: 186–93.
13. Arechavaleta R, Seck T, Chen Y, et al. Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: A randomized, double-blind, non-inferiority trial. Diabetes Obes.Metab. 2011; 13: 160–8.
14. Seck T, Nauck M, Sheng D, 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: 562–76.
15. 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: 959–69.
16. Raz I, Chen Y, Wu M, et al. Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes. Curr. Med. Res. Opin. 2008; 24: 537–50.
17. Kadowaki T, Tajima N, Odawara M, Nishii M, Nonaka K, Stein PP. Sitagliptin added to ongoing treatment with metformin improved glycemic control and was well tolerated in Japanese patients with type 2 diabetes. Diabetes 2008; 57(Suppl 1.): A589–90 (Abstract).
18. 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: 2638–43.
19. 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: 733–45.
20. Harashima SI, Ogura M, Tanaka D, et al. Sitagliptin add-on to low dosage sulphonylureas: Efficacy and safety of combination therapy on glycaemic control and insulin secretion capacity in type 2 diabetes. Int. J. Clin. Pract. 2012; 66: 465–76.
21. Tajima N, Kadowaki T, Odawara M, Nishii M, Taniguchi T, Arjona Ferreira JC: Addition of sitagliptin to ongoing glimepiride therapy in Japanese patients with type 2 diabetes over 52 weeks leads to improved glycemic control. Diabetol Int 2011; 2: 32–44.
22. 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: 1979–87.
23. Williams-Herman D, Xu L, Teng R, et al. Effect of initial combination therapy with sitagliptin and metformin on beta-cell function in patients with type 2 diabetes. Diabetes Obes.Metab. 2012; 14: 67–76.
24. Williams-Herman D, Johnson J, Teng R, Golm G, Kaufman KD, Goldstein BJ, Amatruda JM. 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: 442–51.
25. Williams-Herman D, Johnson J, Teng R, 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: 569–83.
26. Reasner C, Olansky L, Seck TL, et al. The effect of initial therapy with the fixed-dose combination of sitagliptin and metformin compared with metformin monotherapy in patients with type 2 diabetes mellitus. Diabetes Obes.Metab. 2011; 13: 644–52.
27. Reasner CA, Olansky L, Seck T, 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. Diabetologia. 2009; 52: (Suppl 1):S295 (Abstract).
28. Migoya EM, Bergeron R, Miller JL, et al. Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. Clin. Pharmacol. Ther. 2010; 88: 801–8.
29. Mohan V, Yang W, Son HY, 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: 106–16.
30. Yang W, Guan Y, Shentu Y, et al. The addition of sitagliptin to ongoing metformin therapy significantly improves glycemic control in Chinese patients with type 2 diabetes. J.Diabetes. 2012; 4: 227–37.
31. Bloomgarden ZT, Dodis R, Viscoli CM, Holmboe ES, Inzucchi SE. Lower baseline glycemia reduces apparent oral agent glucose-lowering efficacy: A meta-regression analysis. Diabetes Care. 2006; 29: 2137–9.
32. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004; 27: 2628–35.
33. Roberts VL, Stewart J, Issa M, Lake B, Melis R. Triple therapy with glimepiride in patients with type 2 diabetes mellitus inadequately controlled by metformin and a thiazolidinedione: Results of a 30-week, randomized, double-blind, placebo-controlled, parallel-group study. Clin.Ther. 2005; 27: 1535–47.
34. 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: 2564–71.
35. 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: 1556–68.
36. Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: A consensus statement from the American Heart Association and American Diabetes Association. Circulation 108:2941–2948. October 7, 2003; 2003.
37. Merck & Co., Inc. US prescribing information for JANUVIA® (sitagliptin) Tablets, March 2013. 2013. Available at: http://www.januvia.com/sitagliptin/januvia/consumer/prescribing-information-for-januvia/index.jsp, accessed 30 April 2013.
38. Miettinen O, Nurminen M. Comparative analysis of two rates. Stat. Med. 1985; 4: 213–26.