title: Management of cardiovascular risk factors with pioglitazone combination therapies in type 2 diabetes: an observational cohort study.
abstract: BACKGROUND
  Type 2 diabetes (T2D) is strongly associated with cardiovascular risk and requires medications that improve glycemic control and other cardiovascular risk factors. The authors aimed to assess the relative effectiveness of pioglitazone (Pio), metformin (Met) and any sulfonylurea (SU) combinations in non-insulin-treated T2D patients who were failing previous hypoglycemic therapy.
  
  
  METHODS
  Over a 1-year period, two multicenter, open-labeled, controlled, 1-year, prospective, observational studies evaluated patients with T2D (n = 4585) from routine clinical practice in Spain and Greece with the same protocol. Patients were eligible if they had been prescribed Pio + SU, Pio + Met or SU + Met serving as a control cohort, once they had failed with previous therapy. Anthropometric measurements, lipid and glycemic profiles, blood pressure, and the proportions of patients at microvascular and macrovascular risk were assessed.
  
  
  RESULTS
  All study treatment combinations rendered progressive 6-month and 12-month lipid, glycemic, and blood pressure improvements. Pio combinations, especially Pio + Met, were associated with increases in HDL-cholesterol and decreases in triglycerides and in the atherogenic index of plasma. The proportion of patients at high risk decreased after 12 months in all study cohorts. Minor weight changes (gain or loss) and no treatment-related fractures occurred during the study. The safety profile was good and proved similar among treatments, except for more hypoglycemic episodes in patients receiving SU and for the occurrence of edema in patients using Pio combinations. Serious cardiovascular events were rarely reported.
  
  
  CONCLUSIONS
  In patients with T2D failing prior hypoglycemic therapies, Pio combinations with SU or Met (especially Pio + Met) improved blood lipid and glycemic profiles, decreasing the proportion of patients with a high microvascular or macrovascular risk. The combination of Pio with SU or Met may therefore be recommended for T2D second-line therapy in the routine clinical practice, particularly in patients with dyslipidemia.
authors.affiliation: Clinical Research Department, Lilly, SA, Madrid, Spain. rodriguez_angel@lilly.com
authors.forename: Angel
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Jesús
authors.initials: J
authors.lastname: Reviriego
authors.forename: Vasilios
authors.initials: V
authors.lastname: Karamanos
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: del Cañizo
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Vlachogiannis
authors.forename: Vangelis
authors.initials: V
authors.lastname: Drossinos
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure; D015992:Body Mass Index; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006115:Greece; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D016015:Logistic Models; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D000077205:Pioglitazone; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D008687:Metformin; D000077205:Pioglitazone; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human