Intensive therapy in newly diagnosed type 2 diabetes: Results of a 6-year randomized trial

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 β-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 diagnosisVinitial short-term insulin treatment followed by either insulinbased or intensive oral hypoglycemic-based therapyVstabilizes β-Cell function for at least 6 years. Treatment failure was independent of intervention and was associated with worse disease pathology at baseline.