Clinical Pearls & Morning Reports
Rosenstock et al. conducted a phase 2 clinical trial that investigated the efficacy and safety of once-weekly insulin icodec as compared with once-daily insulin glargine in patients who had not received insulin previously and whose type 2 diabetes was inadequately controlled while taking metformin with or without a dipeptidyl peptidase 4 inhibitor. Read the NEJM Original Article here.
Q: What is insulin icodec?
A: Insulin icodec is a basal insulin analogue administered once weekly that is in development for the treatment of patients with diabetes. With a time to maximum concentration of 16 hours and a half-life of approximately 1 week, insulin icodec has a pharmacokinetic and pharmacodynamic profile suitable for once-weekly injection.
Q: How did glycemic control with once-weekly insulin icodec compare with that of once-daily insulin glargine in the trial by Rosenstock et al.?
A: In this 26-week, phase 2 clinical trial, the use of icodec resulted in glycemic control similar to that of once-daily glargine without significantly affecting rates of clinically relevant hypoglycemia. During the trial, a similarly robust reduction in the glycated hemoglobin level was observed with both drugs, with more than two thirds of patients reaching a glycated hemoglobin level of less than 7%; the reduction in the fasting plasma glucose level was also similar in the two groups, and greater improvements in the 9-point patient-measured blood glucose profile were observed with once-weekly insulin icodec than with once-daily glargine, which is currently the most commonly used basal insulin analogue.
A: The observed incidence of level 1 hypoglycemia alerts (blood glucose level, ≥54 and <70 mg per deciliter) was 53.6% in the icodec group and 37.7% in the glargine group, and the observed rates of this end point during the treatment exposure period were 5.09 and 2.11 events per patient-year of exposure for icodec and glargine, respectively (estimated rate ratio, 2.42; 95% CI, 1.50 to 3.88). The higher number of level 1 hypoglycemic events in the icodec group than in the glargine group may reflect the trial design and suggests that the fasting glucose target may need to be slightly higher and the insulin dose increments smaller to ensure an efficacious initiation and adjustment of insulin icodec with even fewer hypoglycemic events. For both icodec and glargine, the observed incidence of combined level 2 (blood glucose level, <54 mg per deciliter ) or level 3 (severe cognitive impairment requiring external assistance for recovery) hypoglycemia was low (16.0% and 9.8%, respectively); the observed event rates were 0.53 and 0.46 events per patient-year of exposure, respectively, with an estimated rate ratio of 1.09 (95% CI, 0.45 to 2.65).
A: No unexpected safety findings occurred with the use of insulin icodec. Approximately 50% of patients in each treatment group had an adverse event. There was no between-group difference in insulin-related key adverse events, and rates of hypersensitivity and injection-site reactions were low. Most adverse events were mild, and no serious events were deemed to be related to the trial medications.