Exp Clin Endocrinol Diabetes 2015; 123(05): 289-295
DOI: 10.1055/s-0034-1396864
Article
© Georg Thieme Verlag KG Stuttgart · New York

The Comparative Effect of Pioglitazone and Metformin on Serum Osteoprotegerin, Adiponectin and Intercellular Adhesion Molecule Concentrations in Patients with Newly Diagnosed Type 2 Diabetes: a Randomized Clinical Trial

A. Esteghamati
1   Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
,
R. Azizi
1   Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
,
M. Ebadi
1   Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
,
S. Noshad
1   Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
,
M. Mousavizadeh
1   Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
,
M. Afarideh
1   Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
,
M. Nakhjavani
1   Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
› Author Affiliations
Further Information

Publication History

received 01 November 2014
first decision 29 November 2014

accepted 10 December 2014

Publication Date:
21 January 2015 (online)

Abstract

Aim: The etiologic role of inflammatory pathways in the development of diabetic complications, especially cardiovascular events, has been established. The anti-inflammatory role of metformin and pioglitazone has been described; however, no study to date has compared the efficacy of these common oral agents in this regard. In this study, the authors aimed to compare the anti-inflammatory properties of pioglitazone and metformin, with respect to their effect on serum concentrations of highly sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG), intercellular adhesion molecule-1 (ICAM-1) and adiponectin.

Methods: In an open-label randomized clinical trial, 117 patients with newly diagnosed type 2 diabetes mellitus were visited; 84 fulfilled the inclusion criteria, and were randomly allocated to 2 arms receiving either 1 000 mg/d metformin or 30 mg/d pioglitazone, respectively. Biochemical assessments were made at baseline and the end of the 3 months trial.

Results: Significant reduction in FPG, insulin and HbA1c in women and men of both arms were observed. Log-hsCRP values significantly decreased in both arms. A decreasing, but non-significant trend in log-OPG levels was observed in women of the metformin arm (p=0.063). A greater reduction in log-ICAM levels was identifiable in men receiving pioglitazone compared to the other arm (p=0.008); in addition, the same trend was observed in log-OPG values (p=0.029). Nonetheless, reduction in log-ICAM and log-OPG levels was comparable between the 2 arms. A significant increase in adiponectin was observed in both men and women in the pioglitazone arm (p<0.001), whereas changes were non-significant in the metformin arm.

Conclusion: Remarkably, patients receiving pioglitazone revealed more significant reduction in inflammatory markers.

 
  • References

  • 1 Esteghamati A, Etemad K, Koohpayehzadeh J et al. Trends in the prevalence of diabetes and impaired fasting glucose in association with obesity in Iran: 2005–2011. Diabetes Res Clin Pract 2014; 103: 319-327
  • 2 Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation 2004; 109: II-2-II-10
  • 3 Knudsen S, Foss C, Poulsen P et al. Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications. Eur J Endocrinol 2003; 149: 39-42
  • 4 Poston RN, Haskard DO, Coucher JR et al. Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am J Pathol 1992; 14495: 665-673
  • 5 Willerson JT. Systemic and local inflammation in patients with unstable atherosclerotic plaques. Prog Cardiovasc Dis 2002; 44: 469-478
  • 6 Shin JY, Shin YG, Chung CH. Elevated serum osteoprotegerin levels are associated with vascular endothelial dysfunction in type 2 diabetes. Diabetes Care 2006; 29: 1664-1666
  • 7 Dhore CR, Cleutjens JP, Lutgens E et al. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2001; 21: 1998-2003
  • 8 Park JS, Cho MH, Nam JS et al. Effect of pioglitazone on serum concentrations of osteoprotegerin in patients with type 2 diabetes mellitus. Eur J Endocrinol 2011; 164: 69-74
  • 9 Yki-Järvinen H. Thiazolidinediones. New Engl J Med 2004; 351: 1106-1118
  • 10 Sung B, Park S, Yu BP et al. Modulation of PPAR in aging, inflammation, and calorie restriction. J Gerontol A Biol Sci Med Sci 2004; 59: 997-1006
  • 11 Isoda K, Young JL, Zirlik A et al. Metformin inhibits proinflammatory responses and nuclear factor-κB in human vascular wall cells. Arterioscler Thromb Vasc Biol 2006; 26: 611-617
  • 12 American Diabetes Association . Diagnosis and classification of diabetes mellitus. Diabetes Care 2013; 36: S67-S74
  • 13 Meriden T. Progress with thiazolidinediones in the management of type 2 diabetes mellitus. Clin Ther 2004; 26: 177-190
  • 14 Mirmiranpour H, Mousavizadeh M, Noshad S et al. Comparative effects of pioglitazone and metformin on oxidative stress markers in newly diagnosed type 2 diabetes patients: A randomized clinical trial. J Diabetes Complications 2013; 27: 501-507
  • 15 Olefsky JM, Saltiel AR. PPAR γ and the treatment of insulin resistance. Trends Endocrinol Metab 2000; 11: 362-368
  • 16 Parulkar AA, Pendergrass ML, Granda-Ayala R et al. Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med 2001; 134: 61-71
  • 17 [Anonymous] . Consensus Development Conference on Insulin Resistance. Diabetes Care 1998; 21: 310-314
  • 18 Haffner SM, Greenberg AS, Weston WM et al. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 2002; 106: 679-684
  • 19 Ridker PM, Rifai N, Rose L et al. Comparison of C-reactive potein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002; 347: 1557-1565
  • 20 Germeyer A, Jauckus J, Zorn M et al. Metformin modulates IL-8, IL-1β, ICAM and IGFBP-1 expression in human endometrial stromal cells. Reprod Biomed Online 2011; 22: 327-334
  • 21 Lihn A, Pedersen SB, Richelsen B. Adiponectin: action, regulation and association to insulin sensitivity. Obesity Rev 2005; 6: 13-21