Background and Objective: Vildagliptin and sitagliptin are oral dipeptidyl peptidase 4 inhibitors approved in Japan for the treatment of type 2 diabetes mellitus when adequate glycaemic control is not achieved with diet, exercise or sulphonylureas. The aim of this study was to compare 12-week glycaemic control with vildagliptin 50 mg twice daily versus sitagliptin 50 or 100 mg once daily in Japanese patients with type 2 diabetes.
Methods: Randomized trials of vildagliptin or sitagliptin in Japanese patients were identified from the literature. Individual patient data were obtained for vildagliptin trials. In the absence of a head-to-head randomized trial, a matching-adjusted indirect comparison was conducted by weighting individual patients from vildagliptin trials to match average baseline characteristics published for sitagliptin trials, including age, sex, body mass index, glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG) and diabetes duration. After matching, HbA1c change from baseline to week 12, the primary endpoint in each trial, was compared between balanced populations treated with vildagliptin and sitagliptin. Separate comparisons were conducted for vildagliptin 50 mg twice daily versus sitagliptin 50 mg and 100 mg once daily.
Results: Two trials of vildagliptin and three trials of sitagliptin were identified for Japanese patients. Across all included trials, a total of 264 patients were treated with vildagliptin 50 mg twice daily, 235 were treated with sitagliptin 50 mg once daily and 145 were treated with sitagliptin 100 mg once daily. Mean baseline HbA1c ranged from 7.4% to 7.8% per trial. Before matching, significant (p<0.05) cross-trial differences included lower mean HbA1c (by 0.2–0.3%) and higher FPG (by 5–13 mg/dL) in vildagliptin trials. After matching, all baseline characteristics were balanced between treatment groups. Combining matched trials, vildagliptin 50 mg twice daily was associated with significantly greater absolute HbA1c reduction by 0.28% compared with sitagliptin 50mg once daily (95% CI 0.15, 0.41; p<0.001) and by 0.35% compared with sitagliptin 100mg once daily (95% CI 0.07, 0.62; p = 0.013).
Conclusion: After adjusting for baseline differences among trials of vildagliptin and sitagliptin in Japanese patients with type 2 diabetes, vildagliptin 50 mg twice daily was associated with significantly greater HbA1c reduction than sitagliptin 50 mg or 100 mg once daily.
Fasting Plasma Glucose Glycaemic Control Sitagliptin Vildagliptin Individual Patient Data
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.
This research was funded by Novartis Pharma AG, Basel, Switzerland. JES, ES, EK, LF and EQW are employees of Analysis Group Inc., which has received research support from Novartis. J-BG is an employee of Novartis Pharma AG.
JES, ES, EK, LF and EQW contributed to the design and conduct of the analyses, and to manuscript development; J-BG contributed to the design of the analyses and manuscript development.
Neville SE, Boye KS, Montgomery WS, et al. Diabetes in Japan: a review of disease burden and approaches to treatment. Diabetes Metab Res Rev 2009; 25(8): 705–16PubMedCrossRefGoogle Scholar
Rosenbloom AL, Joe JR, Young RS, et al. Emerging epidemic of type 2 diabetes in youth. Diabetes Care 1999 Feb 1; 22(2): 345–54PubMedCrossRefGoogle Scholar
Zhang P, Zhang X, Brown J, et al. Global healthcare expenditure on diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010 Mar 1; 87(3): 293–301PubMedCrossRefGoogle Scholar
Green BD, Flatt PR, Bailey CJ. Dipeptidyl peptidase IV (DPP IV) inhibitors: a newly emerging drug class for the treatment of type 2 diabetes. Diabetes Vasc Dis Res 2006 Dec 1;3(3): 159–65CrossRefGoogle Scholar
Ahrén B. Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes. Expert Opin Emerging Drugs 2011 Jan 12; 13(4): 593–607CrossRefGoogle Scholar
Gerich J. DPP-4 inhibitors: what may be the clinical differentiators? Diabetes Res Clin Pract 2010 Nov 1; 90(2): 131–40PubMedCrossRefGoogle Scholar
Marfella R, Barbieri M, Grella R, et al. Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations. J Diabetes Complications 2010 Mar 1; 24(2): 79–83PubMedCrossRefGoogle Scholar
Iwamoto Y, Tajima N, Kadowaki T, et al. Efficacy and safety of sitagliptin monotherapy compared with voglibose in Japanese patients with type 2 diabetes: a randomized, double-blind trial. Diabetes Obesity Metab 2010; 12(7): 613–22CrossRefGoogle Scholar
Iwamoto Y, Taniguchi T, Nonaka K, et al. Dose-ranging efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus. Endocr J 2010; 57(5): 383–94PubMedCrossRefGoogle Scholar
Iwamoto Y, Kashiwagi A, Yamada N, et al. Efficacy and safety of vildagliptin and voglibose in Japanese patients with type 2 diabetes: a 12-week, randomized, double-blind, active-controlled study. Diabetes Obesity Metab 2010; 12(8): 700–8CrossRefGoogle Scholar
Kikuchi M, Abe N, Kato M, et al. Vildagliptin dose-dependently improves glycemic control in Japanese patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2009 Feb 1; 83(2): 233–40PubMedCrossRefGoogle Scholar
Nonaka K, Kakikawa T, Sato A, et al. Efficacy and safety of sitagliptin monotherapy in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract 2008 Feb 1; 79(2): 291–8PubMedCrossRefGoogle Scholar
Fakhoury W, LeReun C, Wright D. A meta-analysis of placebo-controlled clinical trials assessing the efficacy and safety of incretin-based medications in patients with type 2 diabetes. Pharmacology 2010; 86(1): 44–57PubMedCrossRefGoogle Scholar
Richter B, Bandeira-Echtler E, Bergerhoff K, et al. Di-peptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev 2008; 2: CD006739PubMedGoogle Scholar
Bucher HC, Guyatt GH, Griffith LE, et al. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997 Jun 1; 50(6): 683–91PubMedCrossRefGoogle Scholar
Glenny A, Altman D, Song F, et al. Indirect comparisons of competing interventions. Health Technol Assess 2005; 9(26): 1–134, iii-ivPubMedGoogle Scholar
Sutton A, Ades AE, Cooper N, et al. Use of indirect and mixed treatment comparisons for technology assessment. Pharmacoeconomics 2008; 26(9): 753–67PubMedCrossRefGoogle Scholar
Signorovitch JE, Wu EQ, Yu AP, et al. Comparative effectiveness without head-to-head trials: a method for matching-adjusted indirect comparisons applied to psoriasis treatment with adalimumab or etanercept. Pharmacoeconomics 2010; 28(10): 935–45PubMedCrossRefGoogle Scholar
Nonaka K, Tsubouchi H, Okuyama K, et al. Effects of once-daily sitagliptin on 24-h glucose control following 4 weeks of treatment in Japanese patients with type 2 diabetes mellitus. Horm Metab Res 2009; 41(03): 232–7PubMedCrossRefGoogle Scholar
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998 Sep 12; 352(9131): 837–53CrossRefGoogle Scholar
Gilmer TP, O’Connor PJ, Manning WG, et al. The cost to health plans of poor glycemic control. Diabetes Care 1997 Dec 1; 20(12): 1847–53PubMedCrossRefGoogle Scholar
Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995 May 1; 28(2): 103–17PubMedCrossRefGoogle Scholar
Ahrén B, Foley JE, Bosi E. Clinical evidence and mechanistic basis for vildagliptin’s action when added to metformin. Diabetes Obesity Metab 2011; 13(3): 193–203CrossRefGoogle Scholar
Service F, Molnar G, Rosevear J, et al. Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 1970; 19(9): 644–55PubMedGoogle Scholar
DeFronzo RA, Stonehouse AH, Han J, et al. Relationship of baseline HbA1c and efficacy of current glucose-lowering therapies: a meta-analysis of randomized clinical trials. Diabetic Med 2010; 27(3): 309–17PubMedCrossRefGoogle Scholar