Efficacy and safety of Once-Weekly Insulin Icodec

Abstract

Nasser Mikhail

Insulin icodec is a long-acting once-weekly basal insulin analog that is currently under investigations. Efficacy and safety of insulin icodec were assessed in a series of 6 phase 3 clinical trials known as the ONWARDS Program; 5 trials in type 2 diabetes, and 1 trial in type 1 diabetes. In 4 of the 6 ONWARDS trials, reductions in glycated hemoglobin (HbA1c) levels were slightly greater with insulin icodec compared with once-daily insulin glargine or degludec with a mean difference of 0.19-0.38 percentage points. In the other 2 trials, insulin icodec was not inferior to insulin degludec in reducing HbA1c lev- els. Data analysis of continuous glucose monitoring (CGM) showed greater or similar time spent in range (TIR) with insulin icodec versus insulin glargine or degludec. In type 2 diabetes, patient satisfaction and compliance were superior with insulin icodec compared with insulin glargine or degludec. However, in type 1 diabetes, satisfaction score was lower with insulin icodec than with degludec. Incidence of level 1 hypoglycemia [blood glucose (BG) levels 54-69 mg/dl] was higher with insulin icodec compared with insulin glargine or degludec with estimated rate ratio (ERR) ranging from 1.25 to 1.88. In 3 of the 6 ONWARDS trials, incidence of combined level 2 hypoglycemia (clinically significant hypoglycemia with BG < 54 mg/dl) and level 3 hypoglycemia (severe hypoglycemia with cognitive impairment requiring external assistance) was significantly higher (by 71-89%) with insulin icodec vs insulin glargine or degludec. In patients with type 1 diabetes, incidence of hypoglycemia (levels 1, 2, 3, and nocturnal) was substantially higher with insulin icodec versus insulin. In general, no significant differences in weight were recorded between subjects receiving insulin icodec and those receiving insulin degludec. Allergic reactions were not increased with use of insulin icodec. In conclusion, insulin icodec may be a convenient basal insulin that is adminis- tered once weekly. It is similar or slightly higher in efficacy compared with insulin glargine or degludec. Yet, it is associated with increased incidence of hypoglycemia, particularly in type 1 diabetes.

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