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

<b>OBJECTIVE</b><br><b></b><p><b> </b>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 U100 (IGlar U100) in people with type 2 diabetes receiving daily basal insulin and ≥1 oral glucose-lowering medication.</p> <p><b>RESEARCH DESIGN AND METHODS</b><br> This multicenter, open-label, treat-to-target phase 2 trial randomized (1:1:1) eligible basal-insulin-treated (total daily dose 10–50 U) people with type 2 diabetes (HbA<sub>1c</sub> 7.0–10.0% [53.0–13.3 mmol/mo]) to icodec with an initial 100% loading dose (where only the first dose was doubled; icodec LD), icodec with no loading dose (icodec NLD) or IGlar U100 for 16 weeks. Primary endpoint was percent time in <a>range (TIR; 3.9–10.0 mmol/L [70–180 mg/dL]) </a>during weeks 15 and 16, measured using continuous glucose monitoring. Key secondary endpoints included HbA<sub>1c</sub>,<sub> </sub>adverse events (AEs) and hypoglycemia. </p> <p><b>RESULTS</b><br> Estimated mean TIR during weeks 15 and 16 was 72.9% (icodec LD; <i>n</i> = 54), 66.0% (icodec NLD; <i>n</i> = 50) and 65.0% (IGlar U100; <i>n</i> = 50), with a statistically significant difference favoring icodec LD versus IGlar U100 (7.9%-points, 95% CI 1.8 to 13.9%). Mean HbA<sub>1c</sub> 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.<br> <br> </p> <p><b>CONCLUSIONS</b><br> 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.</p>

Clinical Outcomes With Once‐Weekly Insulin Icodec Versus Once‐Daily Insulin Glargine U100 in Insulin‐Naïve and Previously Insulin‐Treated Individuals With Type 2 Diabetes: A Meta‐Analysis of Randomised Controlled Trials

“…Since icodec titration B employed a 28 unit/week adjustment and a prebreakfast goal of 80-130 mg/dL that is in accordance with ADA guidelines, we included this group in our analysis [26]. Additionally, titration A employed a 21 unit/week adjustment, which was different from Rosenstock et al [16] and Bajaj [18] studies, and titration C used a different goal than the glargine U100 group, which could have introduced bias in the results. Furthermore, the Bajaj trial [17] also evaluated two icodec treatment plans, one with and one without an initial loading dosage (LD).…”

“…Furthermore, the Bajaj trial [17] also evaluated two icodec treatment plans, one with and one without an initial loading dosage (LD). The discontinuation of prior basal insulin might cause glycaemic control to worsen since insulin icodec has a half-life of 1 week and reaches its steady state after 3-4 weeks [18,20].…”

“…We included five RCTs in our meta-analysis [16][17][18][19][20]. 2019 individuals with T2DM were included, 1093 in the icodec group and 1006 in the glargine group.…”

“…Male individuals prevailed in all included studies. Previous basal insulin therapy was reported in two trials [18,19], and three trials enrolled insulin-naïve individuals [16,17,20]. The mean age of the participants ranged from 59.1 to 62.4 years, and the mean follow-up duration was 32.4 weeks.…”

Insulin Icodec: A Silver Lining to the Diabetic Cloud

“…The once-weekly insulin icodec achieved a greater reduction in estimated HbA1 of -1.68% points from a baseline HbA1 of 8.9%, compared to -1.31% points for once-daily basal insulins. 27 ONWARDS 6: ONWARDS 6 is a Phase IIIa, 52-week efficacy and safety treat-to-target trial investigating once-weekly insulin icodec vs insulin degludec, both in combination with three daily mealtime insulin injections, in 582 people with type 1 diabetes. The completion of the main phase of the trial is followed by a 26-week extension phase investigating long term safety.…”