Effects of rosiglitazone, glyburide, and metformin on β-cell function and insulin sensitivity in ADOPT

Abstract

Objective: ADOPT (A Diabetes Outcome Progression Trial) demonstrated that initial monotherapy with rosiglitazone provided superior durability of glycemic control compared with metformin and glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine measures of β-cell function and insulin sensitivity from an oral glucose tolerance test (OGTT) over a 4-year period among the three treatments.

Research design and methods: Recently diagnosed, drug-naïve patients with type 2 diabetes (4,360 total) were treated for a median of 4.0 years with rosiglitazone, metformin, or glyburide and were examined with periodic metabolic testing using an OGTT.

Results: Measures of β-cell function and insulin sensitivity from an OGTT showed more favorable changes over time with rosiglitazone versus metformin or glyburide. Persistent improvements were seen in those who completed 4 years of monotherapy and marked deterioration of β-cell function in those who failed to maintain adequate glucose control with initial monotherapy.

Conclusions: The favorable combined changes in β-cell function and insulin sensitivity over time with rosiglitazone appear to be responsible for its superior glycemic durability over metformin and glyburide as initial monotherapy in type 2 diabetes.

FIG. 1.

Baseline adjusted geometric mean levels in the full cohort within each treatment group over 4 years of follow-up for OGTT-derived dynamic measure of the early insulin response (A; insulinogenic index; insulin₃₀ − insulin₀/glucose₃₀ − glucose₀) and insulin sensitivity (B; 1/fasting insulin). Each was analyzed using the log-transformed values, and the results presented are geometric means (± SE asymmetric limits).

FIG. 2.

Baseline adjusted geometric mean levels in the 4-year completer cohort within each treatment group over 4 years of follow-up for OGTT-derived dynamic measure of the early insulin response (A; insulinogenic index; insulin₃₀ − insulin₀/glucose₃₀ − glucose₀) and insulin sensitivity (B; 1/fasting insulin). Each was analyzed using the log-transformed values, and the results presented are geometric means (± SE asymmetric limits).

FIG. 3.

Baseline adjusted geometric mean levels in the 4-year monotherapy failure cohort within each treatment group over 4 years of follow-up for OGTT-derived dynamic measure of the early insulin response (A; insulinogenic index; insulin₃₀ − insulin₀/glucose₃₀ − glucose₀) and insulin sensitivity (B; 1/fasting insulin). Each was analyzed using the log-transformed values, and the results presented are geometric means (± SE asymmetric limits).

FIG. 4.

Vector plot of the joint changes in the baseline adjusted geometric mean levels (± SE asymmetric limits) of the OGTT-derived dynamic measure of the early insulin response (insulinogenic index; insulin₃₀ − insulin₀/glucose₃₀ − glucose₀) and insulin sensitivity (1/fasting insulin) over time within each treatment group over 4 years of follow-up in the full (A), 4-year completer (B), and 4-year monotherapy failure (C) cohorts. The changes are plotted relative to the regression line of the baseline levels (the concave line). The dots represent the baseline measurements, that after 6 months and each annual assessment thereafter, and the arrow the directional change with time. The 95% confidence bands for the baseline relationship are illustrated. The SE limits for the individual time points have been omitted for clarity.