A Randomized, Open-Label Comparison of Once-Weekly Insulin Icodec Titration Strategies Versus Once-Daily Insulin Glargine U100

Abstract

<b>OBJECTIVE</b> <p>Insulin icodec (icodec) is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms.</p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>This was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naïve adults (<i>n</i> = 205) with type 2 diabetes and HbA1c 7–10% while treated with oral glucose-lowering medications initiated once-weekly icodec titrations A (pre-breakfast self-measured blood glucose target, 80–130 mg/dL; adjustment ±21U/week; <i>n</i> = 51), B (80–130 mg/dL; ±28U/week; <i>n</i> = 51), C (70–108 mg/dL; ±28U/week; <i>n</i> = 52), or once-daily insulin glargine U100 (IGlar U100; 80–130 mg/dL; ±4U/day; <i>n</i> = 51), <a>all </a><a>titrated weekly. </a>Percentage time in range (TIR; 70–180 mg/dL) during weeks 15&16 was measured using continuous glucose monitoring.</p> <p><b>RESULTS</b></p> <p>TIR improved from baseline (means: A, 57.0%; B, 55.2%; C, 51.0%; IGlar U100, 55.3%) to weeks 15&16 (estimated mean: A, 76.6%; B, 83.0%; C, 80.9%; IGlar U100, 75.9%). TIR was greater for titration B than for IGlar U100 (estimated treatment difference: 7.08%-points; 95% CI, 2.12%–12.04%; <i>P </i>= 0.005). No unexpected safety signals were observed. Level 2 hypoglycemia (<54 mg/dL) was low in all groups (0.05, 0.15, 0.38, 0.00 events per patient/year for icodec titrations A, B, C, IGlar U100, respectively), with no episodes of severe hypoglycemia.</p> <p><b>CONCLUSION</b></p> <p>Once-weekly icodec was efficacious and well tolerated across all three titration algorithms investigated. <a></a><a></a><a>Icodec titration A (80–130 mg/dL; ±21U/week) displayed the best balance between glycemic control and risk of hypoglycemia.</a> </p>