title: Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus.
abstract: BACKGROUND
  Combination therapy is logical for patients with non-insulin-dependent (type 2) diabetes mellitus, because they often have poor responses to single-drug therapy. We studied the efficacy and physiologic effects of metformin and troglitazone alone and in combination in patients with type 2 diabetes.
  
  
  METHODS
  We randomly assigned 29 patients to receive either metformin or troglitazone for three months, after which they were given both drugs for another three months. Plasma glucose concentrations during fasting and postprandially and glycosylated hemoglobin values were measured periodically during both treatments. Endogenous glucose production and peripheral glucose disposal were measured at base line and after three and six months.
  
  
  RESULTS
  During metformin therapy, fasting and postprandial plasma glucose concentrations decreased by 20 percent (58 mg per deciliter [3.2 mmol per liter], P<0.001) and 25 percent (87 mg per deciliter [4.8 mmol per liter], P<0.001), respectively. The corresponding decreases during troglitazone therapy were 20 percent (54 mg per deciliter [2.9 mmol per liter], P=0.01) and 25 percent (83 mg per deciliter [4.6 mmol per liter], P<0.001). Endogenous glucose production decreased during metformin therapy by a mean of 19 percent (P=0.001), whereas it was unchanged by troglitazone therapy (P=0.04 for the comparison between groups). The mean rate of glucose disposal increased by 54 percent during troglitazone therapy (P=0.006) and 13 percent during metformin therapy (P= 0.03 for the comparison within the group and between groups). In combination, metformin and troglitazone further lowered fasting and postprandial plasma glucose concentrations by 18 percent (41 mg per deciliter [2.3 mmol per liter], P=0.001) and 21 percent (54 mg per deciliter [3.0 mmol per liter], P<0.001), respectively, and the mean glycosylated hemoglobin value decreased 1.2 percentage points.
  
  
  CONCLUSIONS
  Metformin and troglitazone have equal and additive beneficial effects on glycemic control in patients with type 2 diabetes. Metformin acts primarily by decreasing endogenous glucose production, and troglitazone by increasing the rate of peripheral glucose disposal.
authors.affiliation: Section of Endocrinology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Inzucchi
authors.forename: D G
authors.initials: DG
authors.lastname: Maggs
authors.forename: G R
authors.initials: GR
authors.lastname: Spollett
authors.forename: S L
authors.initials: SL
authors.lastname: Page
authors.forename: F S
authors.initials: FS
authors.lastname: Rife
authors.forename: V
authors.initials: V
authors.lastname: Walton
authors.forename: G I
authors.initials: GI
authors.lastname: Shulman
mesh_terms: D000284:Administration, Oral; D001786:Blood Glucose / Q000378:metabolism*; D002839:Chromans / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
chemical_list: D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D008687:Metformin; D000077288:Troglitazone; D005947:Glucose