β-Cell Function Preservation After 3.5 Years of Intensive Diabetes Therapy

Abstract

OBJECTIVE To assess β-cell function preservation after 3.5 years of intensive therapy with insulin plus metformin (INS group) versus triple oral therapy (TOT group) with metformin, glyburide, and pioglitazone. RESEARCH DESIGN AND METHODS This was a randomized trial of 58 patients with treatment-naïve newly diagnosed type 2 diabetes. All patients were treated with insulin and metformin for a 3-month lead-in period followed by random assignment to the INS or TOT group. β-Cell function was assessed using a mixed-meal challenge test at randomization and 6, 12, 18, 30, and 42 months. Analyses were intention to treat and performed with repeated-measures models. RESULTS Completion rates at 3.5 years were 83% in the insulin group and 72% in the TOT group, with good compliance in both groups (87 ± 20% in the INS group vs. 90 ± 15% in the TOT group). β-Cell function was preserved at 3.5 years after diagnosis, with no significant change from baseline or difference between the two groups as measured by area under the curve (AUC) of C-peptide (P = 0.14) or the ratio of C-peptide to glucose AUC (P = 0.7). Excellent glycemic control was maintained in both groups (end-of-study HbA1c 6.35 ± 0.84% in the INS group vs. 6.59 ± 1.94% in the TOT group). Weight increased in both groups over time (from 102.2 ± 24.9 kg to 106.2 ± 31.7 kg in the INS group and from 100.9 ± 23.0 kg to 110.5 ± 31.8 kg in the TOT group), with no significant difference between groups (P = 0.35). Hypoglycemic events decreased significantly over time (P = 0.01) but did not differ between groups (P = 0.83). CONCLUSIONS β-Cell function can be preserved for at least 3.5 years with early and intensive therapy for type 2 diabetes with either insulin plus metformin or triple oral therapy after an initial 3-month insulin-based treatment period.