title: Improved glycemic control with insulin glargine versus pioglitazone as add-on therapy to sulfonylurea or metformin in patients with uncontrolled type 2 diabetes mellitus.
abstract: OBJECTIVE
  To compare glycemic control with add-on insulin glargine versus pioglitazone treatment in patients with type 2 diabetes.
  
  
  METHODS
  This 48-week, multicenter, parallel-group, open-label study randomized 389 adults with poorly controlled type 2 diabetes (glycated hemoglobin A1c [A1C], 8.0% to 12.0%), despite > or =3 months of sulfonylurea or metformin monotherapy, to receive add-on therapy with insulin glargine or pioglitazone. Outcomes included A1C change from baseline to end point (primary), percentage of patients achieving A1C levels < or =7.0%, and changes from baseline in fasting plasma glucose, body mass index, weight, and serum lipids. The safety analysis included incidence of adverse events and rates of hypoglycemia.
  
  
  RESULTS
  At end point, insulin glargine yielded a significantly greater reduction in A1C in comparison with pioglitazone (-2.48% versus -1.86%, respectively; 95% confidence interval, -0.93 to -0.31; P = .0001, 48-week modified intent-to-treat population). Insulin glargine also yielded significantly greater reductions in fasting plasma glucose at all time points (end point difference, -34.9 mg/dL; 95% confidence interval, -47.6 to -22.2; P<.0001). In comparison with pioglitazone, insulin glargine resulted in a lower overall incidence of possibly related treatment-emergent adverse events (12.0% versus 20.7%) and fewer study discontinuations (2.2% versus 9.1%), but a higher rate (per patient-year) of confirmed clinically relevant hypoglycemic episodes (blood glucose <70 mg/dL and all severe hypoglycemia) (4.97 versus 1.04; P<.0001) and severe hypoglycemia (0.07 versus 0.01; P = .0309). Weight and body mass index changes were similar between the 2 treatment groups.
  
  
  CONCLUSIONS
  The addition of insulin glargine early in the diabetes treatment paradigm in patients for whom sulfonylurea or metformin monotherapy had failed resulted in significantly greater improvements in glycemic control in comparison with the addition of pioglitazone. Although severe hypoglycemia was more frequent in patients with insulin glargine therapy, hypoglycemic events occurred in <5% of patients in the insulin glargine treatment group.
authors.affiliation: University of Miami Miller School of Medicine, Eleanor and Joseph Kosow Diabetes Treatment Center, Diabetes Research Institute, Miami, Florida 33136, USA. LMeneghi@med.miami.edu
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Meneghini
authors.forename: Louise
authors.initials: L
authors.lastname: Traylor
authors.forename: Sherwyn L
authors.initials: SL
authors.lastname: Schwartz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010352:Patient Dropouts; D000077205:Pioglitazone; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008055:Lipids; D008687:Metformin; D000077205:Pioglitazone; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human