title: The fixed combination of pioglitazone and metformin improves biomarkers of platelet function and chronic inflammation in type 2 diabetes patients: results from the PIOfix study.
abstract: BACKGROUND
  Type 2 diabetes mellitus (T2DM) is characterized by a proinflammatory and procoagulant condition. This study investigates the impact of a pioglitazone plus metformin therapy on biomarkers of inflammation and platelet activation in comparison to a treatment with glimepiride plus metformin.
  
  
  METHODS
  The study was designed as a multicenter, randomized, double-blinded two-arm trial. Patients with T2DM and dyslipidemia under metformin monotherapy with hemoglobin A1c value between 6.5% and 9.0% were eligible for trial participation. Blood was drawn at baseline and after 24 weeks of treatment from patients of five centers. Markers of inflammation and thrombocyte function (soluble CD40 ligand, thromboxane, vWillebrand factor, adhesion molecules, clotting reaction) were evaluated subsequently in a central laboratory.
  
  
  RESULTS
  A total of 46 patients were included in the final analyses. Mean (± standard deviation) age was 58.5 ± 9.0 years (13 women, 33 men; disease duration 6.3 ± 5.0 years; body mass index 32.0 ± 4.8 kg/m(2)). A total of 25 patients were treated with pioglitazone plus metformin, and 21 patients were in the glimepiride arm. There was a significant decline of E-selectin (-3.7 ± 4.8 ng/ml, p < .001 versus baseline), vWillebrand factor (-19.5 ± 32.0%, p < .05), and high-sensitivity C-reactive protein concentrations (-1.08 ± 0.91 mg/liter, p < .05) in the metformin + pioglitazone arm only (metformin + glimepiride, -0.5 ± 3.4 ng/ml, +1.4 ± 33.2%, + 0.08 ± 0.72 mg/liter, respectively, all not significant). Also, all other surrogate markers for platelet function and inflammation showed slight improvements in the metformin + pioglitazone arm but not in the metformin + glimepiride arm.
  
  
  CONCLUSIONS
  The fixed metformin + pioglitazone combination treatment showed an overall improvement of laboratory surrogate markers, indicating improvement of platelet function and of chronic systemic inflammation, which was not seen with metformin + glimepiride.
authors.affiliation: Institute for Clinical Research and Development, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schöndorf
authors.forename: Petra B
authors.initials: PB
authors.lastname: Musholt
authors.forename: Cloth
authors.initials: C
authors.lastname: Hohberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst
authors.forename: Ute
authors.initials: U
authors.lastname: Lehmann
authors.forename: Winfried
authors.initials: W
authors.lastname: Fuchs
authors.forename: Mirjam
authors.initials: M
authors.lastname: Löbig
authors.forename: Jürgen
authors.initials: J
authors.lastname: Müller
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfützner
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood*; D008024:Ligands; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D000077205:Pioglitazone; D010979:Platelet Function Tests; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013931:Thromboxanes / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; D008024:Ligands; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D013931:Thromboxanes; D014841:von Willebrand Factor; C057619:glimepiride; D008687:Metformin; D000077205:Pioglitazone