Download PDF
Drug Res (Stuttg) 2016; 66(02): 94-99
DOI: 10.1055/s-0035-1549993
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Differences between Mitiglinide/Voglibose Fixed-dose Combination and Glimepiride in Modifying Low-density Lipoprotein Heterogeneity in Japanese Type-2 Diabetic Patients: A Pilot Study

S. Tani
1   Department of Health Planning Center, Nihon University Hospital, Tokyo Japan
2   Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo Japan
,
K. Nagao
2   Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo Japan
,
A. Hirayama
2   Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo Japan
› Author Affiliations
Further Information

Publication History

received 24 March 2015

accepted 26 April 2015

Publication Date:
26 May 2015 (online)

Also available at
   Permissions and Reprints

Abstract

Purpose: The purpose of this study was to compare the effects of mitiglinide/voglibose fixed-dose combination and glimepiride on low-density lipoprotein (LDL)-heterogeneity in type-2 diabetic patients with unstable glycemic control after treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors.

Methods: This was an open-label pilot study in which type-2 diabetic patients were randomly assigned to the mitiglinide/voglibose (fixed-dose combination of mitiglinide 10 mg and voglibose 0.2 mg, n=14) or glimepiride (0.5 mg, n=16).

Results: In the glimepiride group, serum LDL cholesterol (LDL-C) and small-dense (sd) LDL levels decreased significantly (−8.5% and −9.0%), while sd-LDL/LDL-C and an indicator of LDL-particle size, LDL-C/apoB, did not change significantly. In the mitiglinide/voglibose group, serum LDL-C levels did not change, while sd-LDL levels and sd-LDL/LDL-C decreased significantly (−8.6% and −7.9%) and LDL-C/apoB increased significantly (5.8%). Fasting blood glucose levels tended to be reduced to a greater extent in the glimepiride group than in the mitiglinide/voglibose group (−13.9% vs. −8.4%, p=0.08), while the rate of reduction of HbA1c levels tended to be higher in the mitiglinide/voglibose group than in the glimepiride group (−6.9% vs. −3.4%, p=0.09), suggesting differences in fluctuating blood glucose levels between the 2 groups.

Conclusion: There were differences in the effects of mitiglinide/voglibose fixed-dose combination and glimepiride in addition to DPP-4 inhibitors on LDL-metabolism, and this may be related to fluctuations in blood glucose levels after treatment with these agents.

Key words

glimepiride - LDL-heterogeneity - mitiglinide/voglibose fixed-dose combination
 

  • References

  • 1 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; 28: 103-117
    CrossrefPubMedGoogle Scholar
  • 2 Nathan DM, Buse JB, Davidson MB et al., American Diabetes Association; European Association for Study of Diabetes . Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009; 32: 193-203
    CrossrefPubMedGoogle Scholar
  • 3 Ono Y, Kamoshima H, Nakamura A et al. Glycemic/metabolic responses to identical meal tolerance tests at breakfast, lunch and dinner in Japanese patients with type 2 diabetes mellitus treated with a dipeptidyl peptidase-4inhibitor and the effects of adding a mitiglinide/voglibose fixed-dose combination. Expert Opin Pharmacother 2014; 15: 1785-1795
    CrossrefPubMedGoogle Scholar
  • 4 Wu L, Parhofer KG. Diabetic dyslipidemia. Metabolism 2014; 63: 1469-1479
    CrossrefPubMedGoogle Scholar
  • 5 Rana JS, Dunning A, Achenbach S et al. Differences in prevalence, extent, severity, and prognosis of coronary artery disease among patients with and without diabetes undergoing coronary computed tomography angiography: results from 10,110 individuals from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes): an InteRnational Multicenter Registry. Diabetes Care 2012; 35: 1787-1794
    Google Scholar
  • 6 Geisen K. Special pharmacology of the new sulfonylurea glimepiride. Arzneimittelforschung 1988; 38: 1120-1130
    PubMedGoogle Scholar
  • 7 Xu DY, Zhao SP, Huang QX et al. Effects of Glimepiride on metabolic parameters and cardiovascular risk factors in patients with newly diagnosed type 2 diabetes mellitus. Diabetes Res Clin Pract 2010; 88: 71-75
    CrossrefPubMedGoogle Scholar
  • 8 Umpierrez G, Issa M, Vlajnic A. Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial. Curr Med Res Opin 2006; 22: 751-759
    CrossrefPubMedGoogle Scholar
  • 9 Derosa G, Gaddi AV, Piccinni MN et al. Differential effect of glimepiride and rosiglitazone on metabolic control of type 2 diabetic patients treated with metformin: a randomized, double-blind, clinical trial. Diabetes Obes Metab 2006; 8: 197-205
    CrossrefPubMedGoogle Scholar
  • 10 Langenfeld MR, Forst T, Hohberg C et al. Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study. Circulation 2005; 11: 2525-2531
    PubMedGoogle Scholar
  • 11 Inoue M. Tighter control of postprandial hyperglycemia with mitiglinide/voglibose fixed-dose combination in Japanese patients with type 2 diabetes mellitus. Expert Opin Pharmacother 2012; 13: 2257-2268
    CrossrefPubMedGoogle Scholar
  • 12 Ding C, Hsu SH, Wu YJ et al. Additive effects of postchallenge hyperglycemia and low-density lipoprotein particles on the risk of arterial stiffness in healthy adults. Lipids Health Dis 2014; 13: 179
    CrossrefPubMedGoogle Scholar
  • 13 Hirano T, Ito Y, Yoshino G. Measurement of small dense low-density lipoprotein particles. J Atheroscler Thromb 2005; 12: 67-72
    CrossrefPubMedGoogle Scholar
  • 14 Sniderman AD, Blank D, Zakarian R et al. Triglycerides and small dense LDL: the twin Achilles heels of the Friedewald formula. Clin Biochem 2003; 36: 499-504
    CrossrefPubMedGoogle Scholar
  • 15 Schaalan M, El-Abhar HS, Barakat M et al. Westernized-like-diet-fed rats: effect on glucose homeostasis, lipid profile, and adipocyte hormones and their modulation by rosiglitazone and glimepiride. J Diabetes Complications 2009; 23: 199-208
    CrossrefPubMedGoogle Scholar
  • 16 Shakuto S, Oshima K, Tsuchiya E. Glimepiride exhibits prophylactic effect on atherosclerosis in cholesterol-fed rabbits. Atherosclerosis 2005; 182: 209-217
    CrossrefPubMedGoogle Scholar
  • 17 Hadi NR, Al-Amran F, Hussein MA et al. Evaluation of the effects of glimepiride (Amaryl) and repaglinide (novoNorm) on atherosclerosis progression in high cholesterol-fed male rabbits. J Cardiovasc Dis Res 2012; 3: 5-11
    CrossrefPubMedGoogle Scholar
  • 18 Katakami N, Kaneto H, Matsuhisa M et al. Effects of glimepiride and glibenclamide on carotid atherosclerosis in type 2 diabetic patients. Diabetes Res Clin Pract 2011; 92: e20-e22
    CrossrefPubMedGoogle Scholar
  • 19 Tani S, Nagao K, Hirayama A. Association between urinary albumin excretion and low-density lipoprotein heterogeneity following treatment of type 2 diabetes patients with the dipeptidyl peptidase-4 inhibitor, vildagliptin: a pilot study. Am J Cardiovasc Drugs 2013; 13: 443-450
    CrossrefPubMedGoogle Scholar
  • 20 Hirano T, Naito H, Kurokawa M et al. High prevalence of small LDL particles in non-insulin-dependent diabetic patients with nephropathy. Atherosclerosis 1996; 123: 57-72
    CrossrefPubMedGoogle Scholar
  • 21 Ohkura T, Inoue K, Fujioka Y et al. The proinsulin/insulin (PI/I) ratio is reduced by postprandial targeting therapy in type 2 diabetes mellitus: a small-scale clinical study. BMC Res Notes 2013; 6: 453
    CrossrefPubMedGoogle Scholar
  • 22 Konya H, Katsuno T, Tsunoda T et al. Effects of combination therapy with mitiglinide and voglibose on postprandial plasma glucose in patients with type 2 diabetes mellitus. Diabetes Metab Syndr Obes 2013; 6: 317-325
    PubMedGoogle Scholar
  • 23 Terasaki M, Nagashima M, Watanabe T et al. Effects of PKF275-055, a dipeptidyl peptidase-4 inhibitor, on the development of atherosclerotic lesions in apolipoprotein E-null mice. Metabolism 2012; 61: 974-977
    CrossrefPubMedGoogle Scholar
  • 24 Terasaki M, Nagashima M, Nohtomi K et al. Preventive effect of dipeptidyl peptidase-4 inhibitor on atherosclerosis is mainly attributable to incretin's actions in nondiabetic and diabetic apolipoprotein E-null mice. PLoS One 2013; 8: e70933
    CrossrefPubMedGoogle Scholar
  • 25 Kwiterovich Jr PO. Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. Am J Cardiol 2002; 90: 30i-47i
    PubMedGoogle Scholar
  • 26 Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care 2003; 26: 881-588
    CrossrefPubMedGoogle Scholar
  • 27 Tani S, Matsumoto M, Nagao K et al. Association of triglyceride-rich lipoproteins-related markers and low-density lipoprotein heterogeneity with cardiovascular risk: effectiveness of polyacrylamide-gel electrophoresis as a method of determining low-density lipoprotein particle size. J Cardiol 2014; 63: 60-68
    CrossrefPubMedGoogle Scholar