Appraisal of Once-Weekly Insulin Icodec

Insulin icodec is a long-acting basal insulin analog under development that can be administered once weekly. The main purpose of this article is to provide an appraisal on insulin icodec based on available data published in a series of phase 3 clinical trials collectively called the ONWARDS Program. In 3 of the 4 published ONWARDS trials, reductions in glycated hemoglobin (HbA1c) levels were slightly superior with insulin icodec compared with once-daily insulin glargine or degludec with a difference of approximately 0.2 percentage points. In the 4th trial, insulin icodec was not inferior to degludec in decreasing HbA1c values. Data analysis of continuous glucose monitoring (CGM) showed greater or similar time spent in range (TIR) with insulin icodec versus insulin glargine or 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. 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 approximately 2-3 times higher with insulin icodec versus insulin glargine or degludec. Preliminary data in patients with type 1 diabetes showed approximately doubling rates of combined level 2 or 3 hypoglycemia with insulin icodec (19.9 hypoglycemic events per person-year-exposure (PYE) versus insulin degludec (10.3 hypoglycemic events per PYE). Time spent below range (TBR) in CGM was similar between insulin icodec and insulin glargine or degludec. Weight gain was generally similar with use of insulin icodec and insulin glargine or degludec. Yet, in one trial, weight gain was significantly greater with insulin icodec versus degludec, with an estimated treatment difference (ETD) of 1.7 kg. Allergic reactions were not increased with use of insulin icodec compared with glargine or degludec. In conclusion, insulin icodec may be a convenient basal insulin that is administered once weekly. It is at least as effective as insulin glargine or degludec. Yet, it is associated with increased incidence of all levels of hypoglycemia.