Context: Although several studies suggest that improved beta-cell function is a key determinant of glycemic remission in type 2 diabetes, other predictors remain unclear. Objective: The aim of this clamp-based study was to identify predictors of 2-year glycemic remission after short-term intensive insulin treatment. Design: A 2-year follow-up was planned in 124 drug-naive patients with type 2 diabetes who received continuous subcutaneous insulin infusion (CSII) for 2 weeks. Euglycemic-hyperinsulinemic clamps and IV glucose tolerance tests were performed to assess the insulin sensitivity [glucose infusion rate (GIR)] and acute insulin response (AIR) before and after CSII. Results: First-phase insulin secretion was restored, and the GIR was significantly improved (P < 0.0001) after the 2-week CSII. Glycemic remission rates were 47.6% and 30.7% after 12 and 24 months of follow-up, respectively. Cox analysis revealed that a higher post-CSII glucose level [hazard ratio (HR), 1.38; 95% CI, 1.15 to 1.66; P = 0.0005] and older age at diabetes diagnosis (HR, 1.34; 95% CI, 1.05 to 1.72; P= 0.02) accounted for an increased risk of hyperglycemic relapse. A 1 SD increase in the AIR (HR, 0.75; 95% CI, 0.57 to 0.99; P = 0.04), GIR (HR, 0.67; 95% CI, 0.48 to 0.93; P = 0.016) after CSII, and baseline GIR (HR, 0.71; 95% CI, 0.51 to 0.99; P = 0.047) was inversely associated with this risk. Conclusions: Younger age at diabetes diagnosis, higher baseline insulin sensitivity, and lower glucose levels after insulin treatment significantly favored a 2-year glycemic remission. This long-term remission was attributed to both improved insulin sensitivity and enhanced beta-cell function after short-term intensive insulin treatment.