Two-year trial of intermittent insulin therapy vs metformin for the preservation of β-cell function after initial short-term intensive insulin induction in early type 2 diabetes

Aims: To test the hypothesis that induction intensive insulin therapy (IIT) needs to be followed by maintenance therapy to preserve beta-cell function, and to evaluate the impact on beta-cell function over 2 years of two approaches to maintenance therapy: intermittent short-term IIT every 3 months vs daily metformin. Materials and methods: In this trial, 24 adults with a mean type 2 diabetes mellitus (T2DM) duration of 2.0 +/- 1.7 years and glycated haemoglobin (HbA1c) levels 6.4 +/- 0.1% (46 +/- 1.1mmol/mol) were randomized to 3 weeks of induction IIT (glargine, lispro) followed by either repeat IIT for up to 2 weeks every 3 months or daily metformin. Participants underwent serial assessment of beta-cell function using the Insulin Secretion-Sensitivity Index-2 (ISSI-2) on an oral glucose tolerance test every 3 months. Results: The primary outcome of baseline-adjusted ISSI-2 at 2 years was higher in the metformin arm compared with intermittent IIT (245.0 +/- 31.7 vs 142.2 +/- 18.4; P =.008). Baseline-adjusted HbA1c at 2 years (secondary outcome) was lower in the metformin arm (6.0 +/- 0.2% vs 7.3 +/- 0.2%; P =.0006) (42 +/- 2.2 vs 56 +/- 2.2mmol/mol). At study completion, 66.7% of participants randomized to metformin had an HbA1c concentration <= 6.0% (<= 42mmol/mol), compared with 8.3% of those on intermittent IIT (P =.009). There were no differences in insulin sensitivity. C onclusion: After induction IIT, metformin was superior to intermittent IIT for maintaining beta-cell function and glycaemic control over 2 years. The strategy of induction and maintenance therapy to preserve beta-cell function warrants exploration in early T2DM.