Context: Evidence-based strategies to prevent progression of dysglycemia in newly diagnosed type 2 diabetes are needed.

Objective: To undertake a secondary analysis of the Early Diabetes Intervention Program (EDIP) in order to understand the features that were protective against worsening glycemia.

Design: EDIP was a randomized, placebo-controlled trial.

Setting: Two university diabetes centers.

Patients: A total of 219 overweight individuals with fasting glucose < 7.8 mmol/L and 2-hour oral glucose tolerance test (OGTT) glucose > 11.1 mmol/L.

Interventions: Acarbose versus placebo, on a background of dietary recommendations, with quarterly visits to assess glycemia and intervention adherence for up to 5 years.

Main outcome measures: Progression of fasting glucose ≥ 7.8 mmol/L on two consecutive quarterly visits. Cox proportional hazards modeling and ANOVA were performed to evaluate determinants of progression.

Results: Progression-free status was associated with reductions in weight, fasting glucose, 2-hour OGTT glucose, and increases in the high-density lipoprotein/triglyceride ratio. The reduction in fasting glucose was the only effect that remained significantly associated with progression-free status in multivariable Cox modeling. The reduction in fasting glucose was in turn primarily associated with reductions in weight and in 2-hour OGTT glucose. Acarbose treatment did not explain these changes.

Conclusions: In early diabetes, reductions in glucose, driven by reductions in weight, can delay progressive metabolic worsening. These observations underscore the importance of lifestyle management including weight loss as a tool to mitigate worsening of glycemia in newly diagnosed diabetes.