Diabetes Metab J.  2016 Jun;40(3):230-239. 10.4093/dmj.2016.40.3.230.

Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin

• Kim JH
• Kim SS
• Baek HS
• Lee IK
• Chung DJ
• Sohn HS
• Bae HY
• Kim MK
• Park JH
• Choi YS
• Kim YI
• Hahm JR
• Lee CW
• Jo SR
• Park MK
• Lee KJ
• Kim IJ

• KMID: 2308631
• DOI: http://doi.org/10.4093/dmj.2016.40.3.230

Abstract

BACKGROUND
We compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes.
METHODS
The present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin.
RESULTS
The mean changes in HbA1c levels from baseline were -0.94% in the vildagliptin group and -0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were -60.2 mg/dL in the vildagliptin group and -38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040). There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL), and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was -0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002).
CONCLUSION
As an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.

Keyword

Dipeptidyl peptidase 4 inhibitor; Metformin; Thiazolidinediones

MeSH Terms

Blood Glucose
Body Weight
Cholesterol
Hemoglobin A, Glycosylated
Humans
Lipoproteins
Metformin*
Thiazolidinediones
Cholesterol
Lipoproteins
Metformin
Thiazolidinediones

Figure

• 

  Fig. 1 (A) Study design. (B) Patient disposition. bid, twice daily; qd, once daily; FBG, fasting blood glucose.

• 

  Fig. 2 (A) Change in glycosylated hemoglobin (HbA1c) from baseline at 16 weeks. Time-course of mean HbA1c (B), mean fasting plasma glucose (FPG) (C), mean postprandial glucose (D), and mean body weight (E) during 16-week treatment with vildagliptin (closed triangles) or pioglitazone (closed circles) in patients with type 2 diabetes continuing their previous stable metformin dose regimen. Values are presented as mean±standard error. bid, twice daily; qd, once daily.

Reference

1. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014; 103:137–149.

2. Kim DJ. The epidemiology of diabetes in Korea. Diabetes Metab J. 2011; 35:303–308.

3. International Diabetes Federation. IDF diabetes atlas. 6th ed. Brussels: International Diabetes Federation;2013.

4. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015; 38:140–149.

5. Stumvoll M, Haring HU. Glitazones: clinical effects and molecular mechanisms. Ann Med. 2002; 34:217–224.

6. Jin SM, Park CY, Cho YM, Ku BJ, Ahn CW, Cha BS, Min KW, Sung YA, Baik SH, Lee KW, Yoon KH, Lee MK, Park SW. Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group, active-controlled, phase III clinical trial with a 28-week extension. Diabetes Obes Metab. 2015; 17:599–602.

7. Hermansen K, Mortensen LS. Bodyweight changes associated with antihyperglycaemic agents in type 2 diabetes mellitus. Drug Saf. 2007; 30:1127–1142.

8. Schwartz AV. Diabetes, TZDs, and bone: a review of the clinical evidence. PPAR Res. 2006; 2006:24502.

9. Lago RM, Singh PP, Nesto RW. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet. 2007; 370:1129–1136.

10. Profit L, Chrisp P, Nadin C. Vildagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus. Core Evid. 2008; 3:13–30.

11. Lindsay JR, Duffy NA, McKillop AM, Ardill J, O'Harte FP, Flatt PR, Bell PM. Inhibition of dipeptidyl peptidase IV activity by oral metformin in type 2 diabetes. Diabet Med. 2005; 22:654–657.

12. Ahren B, Pacini G, Foley JE, Schweizer A. Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year. Diabetes Care. 2005; 28:1936–1940.

13. Mannucci E, Tesi F, Bardini G, Ognibene A, Petracca MG, Ciani S, Pezzatini A, Brogi M, Dicembrini I, Cremasco F, Messeri G, Rotella CM. Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without type 2 diabetes. Diabetes Nutr Metab. 2004; 17:336–342.

14. Migoya EM, Bergeron R, Miller JL, Snyder RN, Tanen M, Hilliard D, Weiss B, Larson P, Gutierrez M, Jiang G, Liu F, Pryor KA, Yao J, Zhu L, Holst JJ, Deacon C, Herman G, Thornberry N, Amatruda J, Williams-Herman D, Wagner JA, SinhaRoy R. 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; 88:801–808.

15. Kim DJ, Lee MS, Kim KW, Lee MK. Insulin secretory dysfunction and insulin resistance in the pathogenesis of Korean type 2 diabetes mellitus. Metabolism. 2001; 50:590–593.

16. Kim CS, Ko SH, Kwon HS, Kim NH, Kim JH, Lim S, Choi SH, Song KH, Won JC, Kim DJ, Cha BY. Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association. Prevalence, awareness, and management of obesity in Korea: data from the Korea national health and nutrition examination survey (1998-2011). Diabetes Metab J. 2014; 38:35–43.

17. Bolli G, Dotta F, Rochotte E, Cohen SE. Efficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin: a 24-week, randomized, double-blind study. Diabetes Obes Metab. 2008; 10:82–90.

18. Bolli G, Dotta F, Colin L, Minic B, Goodman M. Comparison of vildagliptin and pioglitazone in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Obes Metab. 2009; 11:589–595.

19. Charbonnel B, Schernthaner G, Brunetti P, Matthews DR, Urquhart R, Tan MH, Hanefeld M. Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes. Diabetologia. 2005; 48:1093–1104.

20. Takihata M, Nakamura A, Tajima K, Inazumi T, Komatsu Y, Tamura H, Yamazaki S, Kondo Y, Yamada M, Kimura M, Terauchi Y. Comparative study of sitagliptin with pioglitazone in Japanese type 2 diabetic patients: the COMPASS randomized controlled trial. Diabetes Obes Metab. 2013; 15:455–462.

21. Moller JB, Pedersen M, Tanaka H, Ohsugi M, Overgaard RV, Lynge J, Almind K, Vasconcelos NM, Poulsen P, Keller C, Ueki K, Ingwersen SH, Pedersen BK, Kadowaki T. Body composition is the main determinant for the difference in type 2 diabetes pathophysiology between Japanese and Caucasians. Diabetes Care. 2014; 37:796–804.

22. Fukushima M, Usami M, Ikeda M, Nakai Y, Taniguchi A, Matsuura T, Suzuki H, Kurose T, Yamada Y, Seino Y. Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type 2 diabetes. Metabolism. 2004; 53:831–835.

23. Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000; 43:527–550.

24. Cariou B, Charbonnel B, Staels B. Thiazolidinediones and PPARgamma agonists: time for a reassessment. Trends Endocrinol Metab. 2012; 23:205–215.

25. Cuthbertson J, Patterson S, O'Harte FP, Bell PM. Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in type 2 diabetes. Diabet Med. 2009; 26:649–654.

26. Green BD, Irwin N, Duffy NA, Gault VA, O'Harte F P, Flatt PR. Inhibition of dipeptidyl peptidase-IV activity by metformin enhances the antidiabetic effects of glucagon-like peptide-1. Eur J Pharmacol. 2006; 547:192–199.

27. Suk JH, Lee CW, Son SP, Kim MC, Ahn JH, Lee KJ, Park JY, Shin SH, Kwon MJ, Kim SS, Kim BH, Lee SH, Park JH, Kim IJ. Relationship between cardiovascular disease and brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes (REBOUND) Study Group. Current status of prescription in type 2 diabetic patients from general hospitals in Busan. Diabetes Metab J. 2014; 38:230–239.

28. Kaur K, Kaur R, Mittal N, Arora S, Kaushal S. Comparison of efficacy of add-on therapy of vildagliptin versus pioglitazone among type 2 diabetes mellitus patients inadequately controlled on dual therapy of metformin plus sulfonylurea. Asian J Med Sci. 2014; 5:77–81.