Comparative Effects of Metformin and Pioglitazone on Fetuin-A and Osteoprotegerin Concentrations in Patients With Newly Diagnosed Diabetes: A Randomized Clinical Trial Publisher Pubmed



Esteghamati A¹ ; Afarideh M¹ ; Feyzi S¹ ; Noshad S¹ ; Nakhjavani M¹ Show Affiliations
Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews Published:2015

Abstract

Aims: Fetuin-A is a circulating glycoprotein capable of inhibiting insulin signaling both in vivo and in vitro and is positively associated with insulin resistance. Osteoprotegerin (OPG) acts as a regulatory molecule with increased levels in the early stages of diabetes and atherosclerosis, and is also associated with insulin resistance. We investigated the effects of pioglitazone and metformin as representative insulin-sensitizing therapies on fetuin-A and OPG levels. Materials and methods: In a randomized clinical trial setting (NCT02027103), 88 patients with newly diagnosed type 2 diabetes were randomly assigned to pioglitazone (30 mg/day, n = 46) or metformin (1000 mg/day, n = 42) for 12 weeks. Various anthropometric and metabolic parameters, fetuin-A, OPG, highly sensitive C-reactive protein (hsCRP), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured at baseline and after three months. Results: The reduction in fasting plasma glucose and haemoglobin A1c levels was comparable in the two arms. Pioglitazone resulted in a significant reduction in both fetuin-A and OPG in men, but only fetuin-A in women. Metformin was only effective in lowering OPG levels in women. When compared, both medications were equally effective with regard to fetuin-A and OPG reduction in women (p = 0.413 and 0.359, respectively). In men, pioglitazone more effectively decreased fetuin-A levels in both uni- (p = 0.011) and multivariate models (p = 0.015) and OPG levels in only uni- (p = 0.023) but not the multivariate model (p = 0.547). Conclusions: Metformin and pioglitazone differentially affect fetuin-A levels in patients with diabetes. The level of change may not necessarily be associated with the amelioration of insulin resistance. © 2014 Published by Elsevier Ltd on behalf of Diabetes India.