title: Comparative effects of metformin and pioglitazone on fetuin-A and osteoprotegerin concentrations in patients with newly diagnosed diabetes: A randomized clinical trial.
abstract: OBJECTIVE
  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.
  
  
  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 and osteoprotegrin levels in diabetic women and men. The level of change may not necessarily be associated with the amelioration of insulin resistance.
authors.affiliation: Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: esteghamati@tums.ac.ir.
authors.forename: Alireza
authors.initials: A
authors.lastname: Esteghamati
authors.affiliation: Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: mhafarideh@gmail.com.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Afarideh
authors.affiliation: Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: sahar.feyzi@gmail.com.
authors.forename: Sahar
authors.initials: S
authors.lastname: Feyzi
authors.affiliation: Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: sina.noshad@gmail.com.
authors.forename: Sina
authors.initials: S
authors.lastname: Noshad
authors.affiliation: Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: nakhjavanim@tums.ac.ir.
authors.forename: Manouchehr
authors.initials: M
authors.lastname: Nakhjavani
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D000077205:Pioglitazone; D011379:Prognosis; D045162:Thiazolidinediones / Q000627:therapeutic use*; D060749:alpha-2-HS-Glycoprotein / Q000032:analysis*
chemical_list: C556354:AHSG protein, human; D015415:Biomarkers; D007004:Hypoglycemic Agents; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human; D045162:Thiazolidinediones; D060749:alpha-2-HS-Glycoprotein; D008687:Metformin; D000077205:Pioglitazone
keywords: Fetuin-A; Metformin; Osteoprotegerin; Pioglitazone; Randomized clinical trial