The Effect of Vildagliptin on Visfatin in Korean Patients with Type 2 Diabetes: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Prospective Study

Young Hwan Jang; Dong Hyun In; Jae Kook Yang; Hyuk Jin Moon; Gyu Tae Yoon; Ah Jeong Ryu; Yeo Joo Kim; Eun Young Lee; Hyun Jin Kim; Bon Jeong Ku; Jae Min Lee; Kang Seo Park; In Suk Lee; Jong Min Lee; Dong Mee Lim; Keun Yong Park; Sang Jin Kim

doi:10.4093/jkd.2015.16.4.293

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Jang, In, Yang, Moon, Yoon, Ryu, Kim, Lee, Kim, Ku, Lee, Park, Lee, Lee, Lim, Park, and Kim: The Effect of Vildagliptin on Visfatin in Korean Patients with Type 2 Diabetes: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Prospective Study

Original Article

J Korean Diabetes 2015;16(4):303-309.

Published online: 10 January 2015

DOI: https://doi.org/10.4093/jkd.2015.16.4.293

The Effect of Vildagliptin on Visfatin in Korean Patients with Type 2 Diabetes: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Prospective Study

Young Hwan Jang¹, Dong Hyun In¹, Jae Kook Yang¹, Hyuk Jin Moon¹, Gyu Tae Yoon¹, Ah Jeong Ryu¹, Yeo Joo Kim¹, Eun Young Lee¹, Hyun Jin Kim², Bon Jeong Ku², Jae Min Lee³, Kang Seo Park³, In Suk Lee⁴, Jong Min Lee⁴, Dong Mee Lim⁵, Keun Yong Park⁵, Sang Jin Kim¹

¹Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan

²Department of Internal Medicine, Chungnam National University School of Medicine, Konyang University College of Medicine, Daejeon, Korea

³Department of Internal Medicine, Eulji University Hospital, Konyang University College of Medicine, Daejeon, Korea

⁴Department of Internal Medicine, The Catholic University Daejeon St. Mary's Hospital, Konyang University College of Medicine, Daejeon, Korea

⁵Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea

Corresponding author: Sang Jin Kim Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, 31 Suncheonhyang 6-gil, dongnamgu, Cheonan 31151, Korea, E-mail: ksj1113@schmc.ac.kr

Received 22 April 2015 Revised 4 May 2015 Accepted 11 June 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

The effects of dipeptidyl peptidase-4 inhibitors on adipokines remain obscure. The aim of this study was to evaluate the effect of the addition of vildagliptin on visfatin, an adipokine that represents inflammatory biomarkers of adipose tissue, in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy.

Methods

In this 16-week, double-blind, randomized, parallel-group, placebo-controlled study, 71 patients were randomly assigned to vildagliptin 50 mg twice a day (n = 35) or placebo (n = 36) added to ongoing metformin therapy. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma lipids, and visfatin levels were measured at baseline and 16 weeks after treatment.

Results

After 16 weeks, significant reduction in HbA1c and FPG was observed with vildagliptin add-on treatment compared to placebo (‒0.54 ± 0.52%, P = 0.001 and ‒14.80 ± 19.21 mg/dL, P = 0.004, respectively). However, no other clinically meaningful changes in lipid parameters or visfatin were observed.

Conclusion

Vildagliptin add-on to metformin significantly improved fasting blood glucose and HbA1c. However, in this study, no significant differences in lipid parameters or visfatin level were observed between the two groups.

Keywords: Diabetes mellitus, Type 2, Vildagliptin, Visfatin

References

1. Ouchi N. Parker JL, L ugus JJ, W alsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011; 11:85–97.

2. Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony enhancing factor. Mol Cell Biol. 1994; 14:1431–7.

3. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science. 2005; 307:426–30.

4. Cosford SR, Bajpeyi S, Pasarica M, Albarado DC, Thomas SC, Xie H, Church TS, Jubrias SA, Conley KE, Smith SR. Scheletal muscle NAMPT is induced by exercise in humans. Am J Physiol Endocrinol Metab. 2010; 98:E117–E126.

5. Garten A, Petzold S, Barnikol-Oettler A, Körner A. Thasler WE, Kratzsch J, Kiess W, Gebhardt R. Nicotinamide phosphoribosyltransferase (NAMPT/PBEF-visfatin) is contitutively realsed from human hepatocytes. Biochem Biophys Res Commun. 2010; 391:376–81.

6. Aeghate E. Visfatin: structure, function and relation to diabetes mellitus and other dysfunctions. Curr Med Chem. 2008; 15:1851–62.

7. Sanja Stojsavljević, Marija Gomerčić Palčić, Lucija Virović Jukić, Lea Smirčić Duvnjak, Marko Duvnjak. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014; 20:18070–91.

8. Díaz-Soto G, de Luis DA, Conde-Vicente R, Izaola-Jaurequi O, Ramos C, Romero E. Beneficial effects of liraglutide on adipocytokines, insulin sensitivity parameters and cardiovascular risk biomarkers in patients with Type 2 diabetes: A prospective study. Diabetes Res Clin Pract. 2014; 104:92–6.

9. Matsuzawa Y. Adipocytokines and emerging therapeutic targets. Curr Atheroscler Rep. 2005; 7:58–62.

10. Revollo JR, Körner A, Mills KF, Satoh A, Wang T, Garten A, Dasgupta B, Sasaki Y, Wolberger C, Townsend RR, Milbrandt J, Kiess W, Imai S. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab. 2007; 6:363–75.

11. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I. Retraction. Science. 2007; 318:565.

12. Sonoli SS, Shivprasad S, Prasad CV, Patil AB, Desai PB, Somannavar MS. Visfatin: a review. Eur Rev Med Pharmacol Sci. 2011; 15:9–14.

13. Bala M, Martin J, Kopp A, Hanses F, Buechler C, Schäffler A. In vivo suppression of visfatin by oral glucose uptake: evidence for a novel incretin-like effect by glucagon-like peptide-1 (GLP-1). J Clin Endocrinol Metab. 2011; 96:2493–501.

14. Derosa G, Carbone A, D'Angelo A, Querci F, Fogari E, Cicero AF, Maffioli P. Variations in inflammatory biomarkers following the addition of sitagliptin in patients with type 2 diabetes not controlled with metformin. Intern Med. 2013; 52:2179–87.

15. Ahren B, Gomis R, Standl E, Mills D, Schweizer A. Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care. 2004; 27:2874–80.

16. Pan C, Xing X, Han P, Zheng S, Ma J, Liu J, Lv X, Lu J, Bader G. Efficacy and tolerability of vildagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2012; 14:737–44.

17. Koren S, Shemesh-Bar , Tirosh A, Peleg RK, Berman S, Hamad RA, Vinker S, Golik A, Efrati S. The effect of sitagliptin versus glibenclamide on arterial stiffness, blood pressure, lipids and inflammation in type 2 diabetes mellitus patients. Diabetes Technol Ther. 2012; 14:561–7.

Fig. 1.

Changes of plasma visfatin concentration after 16-weeks treatment. (A) Metformin + Placebo group, (B) Metformin + Vildagliptin group.

Table 1.

Baseline demographic and clinical characteristic of the patients

	Metformin + Vildagliptin (n = 35)	Metformin + Placebo (n = 36)	P-value
Age (y)	53.66 ± 10.94	52.53 ± 10.33	0.656^a
Sex
Male	21 (60.00)	19 (52.80)	0.540^b
Female	14 (40.00)	17 (47.20)
Weight (kg) Height (cm)	68.78 ± 10.78 164.25 ± 8.68	67.19 ± 10.49 163.36 ± 8.10	0.530^a 0.654^a
Waist circumference (cm) BMI (kg/m²)	88.81 ± 8.01 25.39 ± 2.56	86.66 ± 15.34 25.05 ± 2.67	0.464^a* 0.590^a
Duration of diabetes (y)	11.18 ± 5.65	11.61 ± 5.93	0.755^a
HbA1c (%)	7.35 ± 0.73	7.94 ± 1.06	0.008^a
FBS (mg/dL)	134.00 ± 26.99	144.75 ± 36.83	0.166^a
SBP (mm Hg)	127.46 ± 11.59	123.53 ± 12.65	0.177^a
DBP (mm Hg)	75.60 ± 8.50	72.06 ± 8.03	0.075^a
Total cholesterol (mg/dL)	166.54 ± 36.74	164.67 ± 33.73	0.823^a
Total cholesterol (mg/dL) LDL cholesterol (mg/dL)	166.54 ± 36.74 96.26 ± 29.44	164.67 ± 33.73 97.17 ± 32.81	0.823 0.903^a
HDL cholesterol (mg/dL)	43.86 ± 10.42	44.75 ± 10.25	0.717^a
HDL cholesterol (mg/dL) Triglyceride (mg/dL)	43.86 ± 10.42 160.91 ± 98.21	44.75 ± 10.25 143.64 ± 96.77	0.717 0.458^a
Visfatin (ng/mL)	2.68 ± 2.17	2.80 ± 2.63	0.834^a

BMI, body mass index; HbA1c, glycated hemoglobin; FPG, fasting plasma glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; LDL, low-density lipoprotein; HDL, high-density lipoprotein.

^a P-values are for independent t-test,

^b P-values are for chi-square test.

Table 2.

Changes in efficacy from week 0(baseline) to week 16

	Metformin + Placebo group		Metformin + Vildagliptin group
	week 0	week 16	week 0	week 16
Weight (kg)	67.17 ± 10.64	65.60 ± 11.46 ^c	69.02 ± 10.85	68.35 ± 11.34
HbA1c (%)	7.94 ± 1.06	8.14 ± 1.36	7.35 ± 0.73	6.81 ± 0.74 ^c
FPG (mg/dL)	144.75 ± 36.83	148.33 ± 43.75	134.00 ± 26.99	119.20 ± 24.48 ^cd
Total cholesterol (mg/dL)	164.67 ± 33.73	156.78 ± 33.74	166.54 ± 36.74	153.74 ± 30.12 ^a
LDL (mg/dL)	97.17 ± 32.81	88.28 ± 26.22	96.26 ± 29.44	82.17 ± 22.63 ^b
HDL (mg/dL)	44.75 ± 10.25	44.50 ± 12.45	43.86 ± 10.42	42.09 ± 9.93 ^a
Triglyceride (mg/dL)	143.64 ± 96.77	132.03 ± 79.96	160.91 ± 98.21	169.23 ± 100.08
Visfatin (ng/mL)	2.80 ± 2.63	3.94 ± 3.13	2.68 ± 2.17	4.47 ± 3.20 ^b
HOMA-IR (score)	2.41 ± 1.90	2.16 ± 1.69	2.23 ± 1.93	2.05 ± 1.54
HOMA-β (%)	38.13 ± 50.50	31.10 ± 24.36	33.51 ± 22.41	53.25 ± 58.85 ^ad

^a P < 0.05 vs. randomization;

^b P < 0.01 vs. randomization;

^c P < 0.001 vs. randomization;

^d P < 0.05 vs. metformin + placebo. HbA1c, glycosylated hemoglobin; FPG, fasting plasma glucose; LDL, low-density lipoprotein; HDL, high-density lipoprotein.

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