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

Abstract

Objective: Insulin icodec is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms.

Research design and methods: This was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naive adults (n = 205) with type 2 diabetes and HbA_1c 7-10% while treated with oral glucose-lowering medications initiated once-weekly icodec titrations A (prebreakfast self-measured blood glucose target 80-130 mg/dL; adjustment ±21 units/week; n = 51), B (80-130 mg/dL; ±28 units/week; n = 51), or C (70-108 mg/dL; ±28 units/week; n = 52), or once-daily insulin glargine 100 units/mL (IGlar U100) (80-130 mg/dL; ±4 units/day; n = 51), all titrated weekly. Percentage of time in range (TIR) (70-180 mg/dL) during weeks 15 and 16 was measured using continuous glucose monitoring.

Results: TIR improved from baseline (means: A, 57.0%; B, 55.2%; C, 51.0%; IGlar U100, 55.3%) to weeks 15 and 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 to 12.04; P = 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 of exposure for icodec titrations A, B, and C and IGlar U100, respectively), with no episodes of severe hypoglycemia.

Conclusions: Once-weekly icodec was efficacious and well tolerated across all three titration algorithms investigated. The results for icodec titration A (80-130 mg/dL; ±21 units/week) displayed the best balance between glycemic control and risk of hypoglycemia.

Trial registration: ClinicalTrials.gov NCT03951805.

Figure 1

TIR 3.9–10.0 mmol/L (70–180 mg/dL) at baseline and during the last 2 weeks of treatment (weeks 15 and 16) (FAS, N = 205). Baseline values are observed mean values. End-of-treatment values represent estimated mean values. The numbers of patients who had missing or <70% CGM measurements during the last 2 weeks of treatment (weeks 15 and 16) were two for titration A, one for titration B, two for titration C, and one for IGlar U100. Insulin icodec titration A: titration of insulin icodec to a prebreakfast SMBG target of 4.4–7.2 mmol/L (80–130 mg/dL) with dose adjustment of ±21 units. Insulin icodec titration B: titration of insulin icodec to a prebreakfast SMBG target of 4.4–7.2 mmol/L (80–130 mg/dL) with dose adjustment of ±28 units. Insulin icodec titration C: titration of insulin icodec to a prebreakfast SMBG target of 3.9–6.0 mmol/L (70–108 mg/dL) with dose adjustment of ±28 units. IGlar U100: titration of IGlar U100 to a prebreakfast SMBG target of 4.4–7.2 mmol/L (80–130 mg/dL) with dose adjustment of ±4 units. TAR, time above range; TBR, time below range.

Figure 2

Changes in key parameters during the 16-weeks study (FAS, N = 205). Mean change in HbA_1c from baseline to week 16 (A), mean weekly insulin dose over time (B), and mean cumulative function of number of severe (level 3) and clinically significant (level 2) hypoglycemic events when subjects were on treatment (C). Observed data: mean (symbol) ± SEM (A) and geometric mean (symbol) ± SEM on log-scale backtransformed (B). Insulin icodec titration A: titration of insulin icodec to a prebreakfast SMBG target of 4.4–7.2 mmol/L (80–130 mg/dL) with dose adjustment of ±21 units. Insulin icodec titration B: titration of insulin icodec to a prebreakfast SMBG target of 4.4–7.2 mmol/L (80–130 mg/dL) with dose adjustment of ±28 units. Insulin icodec titration C: titration of insulin icodec to a prebreakfast SMBG target of 3.9–6.0 mmol/L (70–108 mg/dL) with dose adjustment of ±28 units. IGlar U100: titration of IGlar U100 to a prebreakfast SMBG target of 4.4–7.2 mmol/L (80–130 mg/dL) with dose adjustment of ±4 units. U, units. *Estimated mean values and the corresponding CIs at week 16 derived based on multiple imputation.