title: Long-term effects on lipids and lipoproteins of pioglitazone versus gliclazide addition to metformin and pioglitazone versus metformin addition to sulphonylurea in the treatment of type 2 diabetes.
abstract: OBJECTIVE
  The aim of this study was to determine the long-term effects of pioglitazone add-on to metformin or sulphonylurea on plasma lipids and lipoproteins.
  
  
  METHODS
  The effects of pioglitazone were studied in two clinical trials in patients with inadequately controlled type 2 diabetes (HbA1c > or =7.5 and < or =11%). In the first trial, patients currently receiving metformin were randomised to pioglitazone (15-45 mg/day, n=317) or gliclazide (80-320 mg/day, n=313) add-on therapy. In the second study, pioglitazone (15-45 mg/day, n=319) or metformin (850-2,550 mg/day, n=320) was added to sulphonylurea therapy. Patients were force-titrated to the maximum tolerated dose of add-on therapy, which was maintained to the 2-year endpoint.
  
  
  RESULTS
  There were no statistically significant differences between the groups with respect to HbA1c reduction from baseline to week 104. Whether added to metformin or sulphonylurea, pioglitazone caused highly significant greater decreases in triglycerides and increases in HDL cholesterol from baseline to week 104 than treatments with gliclazide or metformin add-on therapies (p< or =0.001). The triglyceride reductions noted with pioglitazone were maintained over time, with decreases of 16-18% at 1 year and 17-23% at 2 years. In the pioglitazone groups, the improvement in HDL cholesterol at 1 year was maintained, with 21-22% augmentations at 2 years (p<0.001 between-group difference). Small but statistically significant greater reductions in LDL cholesterol were observed with gliclazide vs pioglitazone add-on to metformin and metformin vs pioglitazone add-on to sulphonylurea (p<0.001 for between-group difference). In the pioglitazone groups, mean LDL cholesterol at 2 years was similar to mean baseline LDL cholesterol.
  
  
  CONCLUSIONS
  After 2 years, highly significant decreases in triglycerides and increases in HDL cholesterol that were sustained over time or even improved were observed when pioglitazone was added to metformin or sulphonylurea therapy. These effects of pioglitazone on lipids may be potentially beneficial in reducing cardiovascular risk in type 2 diabetes.
authors.affiliation: Department of Medicine, University College London, Sir Jules Thorn Institute, The Middlesex Hospital, 5th Floor, Mortimer Street, London, W1N 8AA, UK. j.betteridge@ucl.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Betteridge
authors.forename: B
authors.initials: B
authors.lastname: Vergès
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy; D005907:Gliclazide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D000077205:Pioglitazone; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007004:Hypoglycemic Agents; D008055:Lipids; D008074:Lipoproteins; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D014280:Triglycerides; D008687:Metformin; D005907:Gliclazide; D000077205:Pioglitazone