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Weekly Insulin Icodec in Type 2 Diabetes Without Previous Insulin

In the phase 3a ONWARDS 1 trial, weekly doses of the investigational agent insulin icodec produced significantly better glycemic control than once-daily insulin glargine U100 in adults with type 2 diabetes who had not previously received insulin. Reductions in glycated hemoglobin with icodec were sustained through week 78 of the study.

The open-label, treat-to-target phase 3a trial included a 52-week main phase and a 26-week extension phase, plus a 5-week follow-up period. Insulin-naive adults with glycated hemoglobin levels of 7% to 11% who had not previously received insulin were randomized to once-weekly insulin icodec or once-daily insulin glargine U100.

Based on a primary endpoint of the change in the glycated hemoglobin level from baseline to week 52, the study showed: “Each group included 492 participants. Baseline characteristics were similar in the two groups. The mean reduction in the glycated hemoglobin level at 52 weeks was greater with icodec than with glargine U100 (from 8.50% to 6.93% with icodec [mean change, −1.55 percentage points] and from 8.44% to 7.12% with glargine U100 [mean change, −1.35 percentage points]); the estimated between-group difference (−0.19 percentage points; 95% confidence interval [CI], −0.36 to −0.03) confirmed the noninferiority (P <0.001) and superiority (P = 0.02) of icodec. The percentage of time spent in the glycemic range of 70 to 180 mg per deciliter was significantly higher with icodec than with glargine U100 (71.9% vs. 66.9%; estimated between-group difference, 4.27 percentage points [95% CI, 1.92 to 6.62]; P <0.001), which confirmed superiority. Rates of combined clinically significant or severe hypoglycemia were 0.30 events per person-year of exposure with icodec and 0.16 events per person-year of exposure with glargine U100 at week 52 (estimated rate ratio, 1.64; 95% CI, 0.98 to 2.75) and 0.30 and 0.16 events per person-year of exposure, respectively, at week 83 (estimated rate ratio, 1.63; 95% CI, 1.02 to 2.61). No new safety signals were identified, and incidences of adverse events were similar in the two groups.”

Editorial: “In order to move weekly insulin administration safely into clinical practice, it will be important to establish parameters for patient-directed dose adjustment to achieve timely glycemic control,” writes an editorialist. “In contrast to once-weekly GLP-1 receptor agonists, gradual changes in glycemia with cautious dose adjustment may limit the patient’s self-efficacy. Providers need to set expectations that prioritize safety. In addition, whereas cardioprotective weight-loss agents with glucose-lowering efficacy have been acceptable to patients as weekly injectable therapy, insulin is different. Patients and providers commonly avoid adding insulin, perceiving it as a sign of failure. We need to change the conversation about insulin, acknowledging the stigma attached and emphasizing a no-judgment approach — simply put, insulin works to improve glucose control.”

Source: New England Journal of Medicine