Short‐term intensive insulin as induction and maintenance therapy for the preservation of beta‐cell function in early type 2 diabetes (RESET‐IT Main): A 2‐year randomized controlled trial

Abstract Aim To test the hypothesis that the addition of periodic courses of short‐term intensive insulin therapy (IIT) could enhance the effect of metformin (MET) maintenance therapy on preservation of beta‐cell function following induction IIT. Methods In this multicentre, randomized controlled trial, 108 adults with type 2 diabetes (median 1.3 years’ duration; HbA1c 6.6% ± 0.6%) were randomized to 3 weeks of induction IIT (glargine, lispro) followed by MET maintenance, either with or without periodic 2‐week courses of IIT every 3 months for 2 years. Beta‐cell function was assessed by the Insulin Secretion Sensitivity Index‐2 (ISSI‐2) at an oral glucose tolerance test every 3 months. Results In both arms, induction IIT increased ISSI‐2, improved whole‐body insulin sensitivity and reduced hepatic insulin resistance (all P ≤ .0004). The primary outcome of baseline‐adjusted ISSI‐2 at 2 years was not improved by the addition of intermittent IIT (MET + IIT) and was slightly higher in the MET arm (baseline‐adjusted difference −35 [95% CI: −66, –3]), with three additional beta‐cell measures showing no significant differences. Baseline‐adjusted HbA1c at 2 years did not differ between MET and MET + IIT (6.3% ± 0.1% vs. 6.4% ± 0.1%, P = .46), with 32.6% of participants in each arm maintaining HbA1c of 6.0% or less at 2 years. Conclusion Although initial induction IIT induces metabolic improvement, subsequent repeat courses of IIT every 3 months do not further enhance the effect of MET maintenance therapy on beta‐cell function.