Insulin regimen simplification can maintain glycemic control while reducing treatment burden in people with long-standing type 2 diabetes mellitus (T2DM). This phase IV randomized controlled trial, published in Diabetes, Obesity and Metabolism, evaluated transition from MDIs to a once-daily fixed-ratio combination of insulin glargine 100 U/mL and a glucagon-like peptide-1 receptor agonist (GLP-1 RA).

Adults with T2DM were enrolled across five centers and randomized to either continuation of MDIs or initiation of the fixed-ratio basal insulin-GLP-1 RA combination. Eligibility criteria included age 18-80 years, HbA1c ≤9.0%, total daily insulin dose ≤0.8 IU/kg, and preserved fasting C-peptide levels. The active treatment period was 24 weeks, and the primary endpoint was change in HbA1c from baseline.

Ninety participants were analyzed (45 per group). Mean age was 66.2 ± 8.7 years, 79.0% were male, mean HbA1c was 7.9 ± 1.0%, diabetes duration was 17.5 ± 8.7 years, and mean BMI was 33.6 ± 5.5 kg/m². The between-group difference in HbA1c change was −0.12% (95% CI −0.48 to 0.23), indicating comparable glycemic control.

Significant between-group differences favored the once-daily combination therapy. Body weight declined by −4.19 kg, BMI by −1.49 kg/m², and total daily insulin dose by −28.57 IU. Time spent in level 2 hyperglycemia decreased by −4.9%, and the glycemia risk index improved by −13.6.

These findings show that once-daily basal insulin-GLP-1 RA therapy enables insulin de-intensification without loss of glycemic control in T2DM.