title: Intensive therapy in newly diagnosed type 2 diabetes: results of a 6-year randomized trial.
abstract: BACKGROUND
  This study aimed to assess the efficacy of early intensive diabetes therapy with either insulin plus metformin (INS) or triple oral therapy (TOT) with metformin, glyburide, and pioglitazone on glycemic control and A-cell function.
  
  
  METHODS
  Fifty-eight treatment-naive newly diagnosed patients with type 2 diabetes underwent a 3-month lead-in treatment period with insulin and metformin, then were randomized to INS or TOT for 6 years. β-Cell function was measured using mixed-meal challenge test. β-Cell function remained stable throughout the 6-year study in both groups, as measured by the C-peptide area under the curve (AUC; P = 0.13), the AUC C-peptide/AUC glucose (P = 0.9), and by the disposition index (P = 0.8). Excellent glycemic control was maintained in both groups (end-of-study hemoglobinA1c, 7.3% [SD, 1.7%] INS vs 6.4% [1.4%] TOT; P = 0.4). There were 8 treatment failures (confirmed hemoglobinA1c, 98%) in INS and 6 in TOT (P = 0.93). The predictors of treatment failure included higher fasting glucose (P = 0.008), fasting C-peptide (P = 0.008), systolic blood pressure (P = 0.004), and lower insulin sensitivity (P = 0.04) at randomization.
  
  
  CONCLUSIONS
  Early intensive treatment at the time of type 2 diabetes diagnosis-initial short-term insulin treatment followed by either insulin-based or intensive oral hypoglycemic-based therapy-stabilizes β-cell function for at least 6 years. Treatment failure was independent of intervention and was associated with worse disease pathology at baseline.
authors.affiliation: From the Divisions of *Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, †Biostatistics, Department of Clinical Sciences, ‡Mineral Metabolism, Department of Internal Medicine, and §Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: Harrison
authors.forename: Beverley
authors.initials: B
authors.lastname: Adams-Huet
authors.forename: Xilong
authors.initials: X
authors.lastname: Li
authors.forename: Philip
authors.initials: P
authors.lastname: Raskin
authors.forename: Ildiko
authors.initials: I
authors.lastname: Lingvay
mesh_terms: D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011788:Quality of Life; D012307:Risk Factors; D011795:Surveys and Questionnaires; D017211:Treatment Failure
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin