Low-Dose Combination Therapy for Impaired Glucose Tolerance
Low-Dose Combination Therapy for Impaired Glucose Tolerance
Objective—In the Canadian Normoglycemia Outcome Evaluation (CANOE) trial, low-dose rosiglitazone/metformin reduced the risk of diabetes in subjects with impaired glucose tolerance by 66% over a median of 3.9 years. We evaluate the temporal changes in glycemic control, insulin sensitivity, and β-cell function during this trial.
Research Design and Methods—CANOE participants (n = 207) underwent annual oral glucose tolerance testing, enabling temporal comparison of glycemia, insulin sensitivity (Matsuda index), and β-cell function (insulin secretion-sensitivity index-2 [ISSI-2]) between the rosiglitazone/metformin and placebo arms.
Results—Glycemic parameters and insulin sensitivity improved in the rosiglitazone/metformin arm in year 1, but deteriorated in the years thereafter as in the placebo arm. Generalized estimating equation analysis confirmed that both insulin sensitivity and β-cell function decreased over time (Matsuda: β = −0.0515, P < 0.0001; ISSI-2: β = −6.6507, P < 0.0001), with no significant time-by-treatment interaction (Matsuda: P = 0.57; ISSI-2: P = 0.22).
Conclusions—Despite preventing incident diabetes, low-dose rosiglitazone/metformin did not modify the natural history of worsening insulin resistance and β-cell dysfunction.
Although lifestyle modification and antidiabetic medications can prevent the development of type 2 diabetes (T2D) in patients with impaired glucose tolerance (IGT), the long-term durability of these interventions will likely depend on their capacity to modify the insulin resistance and β-cell dysfunction that is characteristic of T2D. The recently reported Canadian Normoglycemia Outcome Evaluation (CANOE) trial was a double-blind, placebo-controlled trial in which low-dose rosiglitazone/metformin therapy was shown to reduce the risk of incident T2D in subjects with IGT by 66% over a median of 3.9 years. For insight on the disease-modifying capacity of this intervention, we conducted the current analysis to compare the temporal changes over time in glycemic control, insulin sensitivity, and β-cell function between the study arms during this trial.
Abstract and Introduction
Abstract
Objective—In the Canadian Normoglycemia Outcome Evaluation (CANOE) trial, low-dose rosiglitazone/metformin reduced the risk of diabetes in subjects with impaired glucose tolerance by 66% over a median of 3.9 years. We evaluate the temporal changes in glycemic control, insulin sensitivity, and β-cell function during this trial.
Research Design and Methods—CANOE participants (n = 207) underwent annual oral glucose tolerance testing, enabling temporal comparison of glycemia, insulin sensitivity (Matsuda index), and β-cell function (insulin secretion-sensitivity index-2 [ISSI-2]) between the rosiglitazone/metformin and placebo arms.
Results—Glycemic parameters and insulin sensitivity improved in the rosiglitazone/metformin arm in year 1, but deteriorated in the years thereafter as in the placebo arm. Generalized estimating equation analysis confirmed that both insulin sensitivity and β-cell function decreased over time (Matsuda: β = −0.0515, P < 0.0001; ISSI-2: β = −6.6507, P < 0.0001), with no significant time-by-treatment interaction (Matsuda: P = 0.57; ISSI-2: P = 0.22).
Conclusions—Despite preventing incident diabetes, low-dose rosiglitazone/metformin did not modify the natural history of worsening insulin resistance and β-cell dysfunction.
Introduction
Although lifestyle modification and antidiabetic medications can prevent the development of type 2 diabetes (T2D) in patients with impaired glucose tolerance (IGT), the long-term durability of these interventions will likely depend on their capacity to modify the insulin resistance and β-cell dysfunction that is characteristic of T2D. The recently reported Canadian Normoglycemia Outcome Evaluation (CANOE) trial was a double-blind, placebo-controlled trial in which low-dose rosiglitazone/metformin therapy was shown to reduce the risk of incident T2D in subjects with IGT by 66% over a median of 3.9 years. For insight on the disease-modifying capacity of this intervention, we conducted the current analysis to compare the temporal changes over time in glycemic control, insulin sensitivity, and β-cell function between the study arms during this trial.
