Switching to Once-Weekly Insulin Icodec Versus Once-Daily Insulin Glargine U100 in Type 2 Diabetes Inadequately Controlled on Daily Basal Insulin: A Phase 2 Randomized Controlled Trial

Abstract

Objective: Insulin icodec (icodec) is a novel once-weekly basal insulin analog. This trial investigated two approaches for switching to icodec versus once-daily insulin glargine 100 units/mL (IGlar U100) in people with type 2 diabetes receiving daily basal insulin and one or more oral glucose-lowering medications.

Research design and methods: This multicenter, open-label, treat-to-target phase 2 trial randomized (1:1:1) eligible basal insulin-treated (total daily dose 10-50 units) people with type 2 diabetes (HbA_1c 7.0-10.0% [53.0-85.8 mmol/mol]) to icodec with an initial 100% loading dose (in which only the first dose was doubled [icodec LD]), icodec with no loading dose (icodec NLD), or IGlar U100 for 16 weeks. Primary end point was percent time in range (TIR; 3.9-10.0 mmol/L [70-180 mg/dL]) during weeks 15 and 16, measured using continuous glucose monitoring. Key secondary end points included HbA_1c, adverse events (AEs), and hypoglycemia.

Results: Estimated mean TIR during weeks 15 and 16 was 72.9% (icodec LD; n = 54), 66.0% (icodec NLD; n = 50), and 65.0% (IGlar U100; n = 50), with a statistically significant difference favoring icodec LD versus IGlar U100 (7.9%-points [95% CI 1.8-13.9]). Mean HbA_1c reduced from 7.9% (62.8 mmol/mol) at baseline to 7.1% (54.4 mmol/mol icodec LD) and 7.4% (57.6 mmol/mol icodec NLD and IGlar U100); incidences and rates of AEs and hypoglycemic episodes were comparable.

Conclusions: Switching from daily basal insulin to once-weekly icodec was well tolerated and provided effective glycemic control. Loading dose use when switching to once-weekly icodec significantly increased percent TIR during weeks 15 and 16 versus once-daily IGlar U100, without increasing hypoglycemia risk.

Trial registration: ClinicalTrials.gov NCT03922750.

Figure 1

TIR during the last 2 weeks of the treatment period (full analysis set). TIR was the primary end point. TAR, time above range; TBR, time below range.

Figure 2

Key parameters during the trial. A: Mean change in HbA_1c from baseline to week 16 (FAS). B: Mean change in FPG from baseline to week 16 (FAS). C: Mean prebreakfast SMBG levels over time (FAS). D: Mean weekly insulin dose over time (FAS). E: Cumulative number of level 1 (“alert” value) hypoglycemic episodes per patient (SAS). F: Cumulative number of level 2 (clinically significant) or level 3 (severe) hypoglycemic episodes per patient (SAS). Observed data. A–C: Mean ± SEM. D: Geometric mean ± SEM on log-scale back transformed. For C, SMBG was assessed with a blood glucose meter as plasma equivalent of capillary whole blood glucose. For D, the dose for a given visit represents the total dose during the preceding week, and weekly IGlar U100 doses were derived as seven times the average daily dose during the preceding week. *Estimated mean values and the corresponding CI at week 16 derived based on multiple imputation. FAS, full analysis set; SAS, safety analysis set; U, unit.