Insulin therapy DE-intensificAtion with iGlarLixi: A phase 4, open-label, parallel-group randomised controlled trial.

AIMS: To evaluate the efficacy and safety of transitioning from multiple daily injections (MDIs) insulin regimen to once-daily, fixed-ratio combination of basal insulin analog glargine 100 U/mL and a glucagon-like peptide 1 receptor agonist lixisenatide (iGlarLixi) in people with type 2 diabetes (PwT2D). MATERIALS AND METHODS: Insulin therapy DE-intensificAtion with iglarLixi was a five-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period. Eligible PwT2D (age 18-80 years, HbA1c ≤9% [75 mmol/mol], total daily dose of insulin ≤0.8 IU/kg, and fasting C-peptide above the lower limit of normal) were randomised in a 1:1 fashion to iGlarLixi initiation or continuation with MDI regimen. The primary endpoint was the mean change in HbA1c from baseline to 24 weeks after randomisation between the two treatment groups. RESULTS: Ninety individuals (n = 45 in both treatment groups), 71/91 (79.0%) male with mean (SD) age 66.2 (8.7) years, HbA1c 7.9 (1.0) % (62.8 [10.9] mmol/mol), diabetes duration 17.5 (8.7) years and body mass index (BMI) 33.6 (5.5) kg/m were analysed. The mean (95% confidence interval) difference in the change in HbA1c between the iGlarLixi and the MDI group was -0.12 (-0.48, 0.23)% (-1.39 [-5.21, 2.43] mmol/mol), indicating comparable glycaemic control in both treatment groups. Significant between-group differences in favour of iGlarLixi were observed in body weight: -4.19 (-5.95, -2.43) kg, BMI: -1.49 (-2.11, -0.86) kg/m, total daily dose of insulin: -28.57 (-34.89, -22.24) IU, time spent in level 2 hyperglycaemia: -4.9 (-9.4, -0.34)%, and glycaemia risk index: -13.6 (-25.1, -2.1). CONCLUSIONS: Insulin therapy simplification from MDI regimen to once-daily iGlarLixi is an efficient and safe treatment option for PwT2D.