Once-A-Week Insulin Will Happen

The end to every day insulin use may be in sight with the development of weekly insulin icodec.

Adherence to medications is usually tricky for patients with diabetes. Most people believe that a decrease in the number of injections in patients with a diabetes drug regimen will improve their compliance. Insulin icodec is the new once-weekly basal insulin analog and is under development to treat patients with diabetes. Insulin icodec could quickly improve glycemic control among patients with diabetes, as well as patients’ adherence and acceptance. Previous data implied that patients with diabetes usually desire medication regimens with few injections and greater flexibility. Insulin icodec has a half-life of approximately one week and a peak of 16 hours. This trial is based on the conclusions in a phase 2 clinical trial that was aimed to research the efficacy and safety of once-weekly insulin icodec as compared with once-daily insulin glargine U100 in patients who had not received insulin previously and whose type 2 diabetes was inadequately controlled while on metformin with or without a dipeptidyl peptidase four inhibitor. 

The study design was a double-blinded, double-dummy, treat to target, active-controlled, parallel-group, multinational phase 2 trial. In a 1 to 1 ratio, patients were randomly placed in either once-weekly subcutaneous icodec plus once-daily placebo or once-daily subcutaneous glargine plus once-weekly placebo. There was a total of 247 patients. The insulin icodec arm had 125 patients, and the insulin glargine arm had 122 patients. There were four patients from the icodec group and seven patients from the glargine group that ended treatment. One patient from the icodec group and two patients from the glargine group started an ancillary treatment. In the baseline patient results, the icodec arm had a longer duration of patients with diabetes. However, besides the slight differences in diabetes, the baseline characteristics were similar between the two study arms. 

The primary endpoint was the patients’ change in their glycated hemoglobin level from baseline to week 26. The secondary endpoints were the patients’ fasting blood glucose changes, body weight, and the mean 9-point patient measured blood glucose data based on their baseline to week 26, and the last two weeks weekly insulin dose mean. Hypoglycemia incidents and insulin associated adverse effects were the safety endpoints in this trial. The statistical analysis for the sample size was determined by a two sides 95% confidence interval. Whether or not the patients were taking dipeptidyl peptidase-four inhibitors stratified the randomization of this trial. 

The mean glycated hemoglobin level at the baseline to week 26 for the icodec arm and glargine arm had a 95% confidence interval [CI], −0.38 to 0.02; P=0.08. The projected percentages of patients getting a glycated hemoglobin level of less than 7% at week 26 were 72% in the icodec group, and 68% in the glargine group and the estimated odds ratio was 1.20 and 95% CI of 0.98 to 2.13. The patients reaching a glycated hemoglobin level percentage of 6.5% or less were 49% and 39%, respectively, with an estimated odds ratio of 1.47 and 95% CI of 0.85 to 2.52. Based on patients’ self-monitoring data, the blood glucose levels were always lower in the icodec group. The icodec arm had a better decrease in the mean 9-point patient measured blood glucose data based on their baseline to week 26, and the last two weeks weekly insulin dose mean. The body weight results were similar in both arms. The results for hypoglycemia events in the icodec group were 0.53 events per year, and the glargine group was 0.46 per year with an estimated rate ratio of 1.09; 95% and CI of 0.45 to 2.65.  

In conclusion, once-weekly insulin icodec does have both a glucose-lowering efficacy and a safety profile like once-daily dosing insulin glargine in patients with type 2 diabetes. Even though the primary endpoint was not significant, it was beneficial for this trial to be a double-blind, double-dummy design, and for most of the patients to complete therapy to week 26. Further studies should be done to approve effectiveness and monitor side effects for insulin icodec.  

Practice Pearls: 

• Patients with diabetes are typically more likely to adhere to their insulin regimen with fewer injections. 
• Insulin Icodec has favorable side effects. 
• The pharmacokinetic and pharmacodynamic data supports insulin icodec being fit to be a once-weekly insulin injection. 

Rosenstock J, Bajaj HS, Janež A, et al. Once-Weekly Insulin for Type 2 Diabetes 

without Previous Insulin Treatment. N Engl J Med. Published online September 22, 

2020:NEJMoa2022474. doi:10.1056/NEJMoa2022474 

Alexandria Bartley, PharmD. Candidate, Florida Agricultural & Mechanical University, College of Pharmacy and Pharmaceutical Sciences 

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