Once-weekly treatment with insulin icodec, an investigational treatment not yet approved by the FDA, had glucose-lowering efficacy and a safety profile similar to those of once-daily insulin glargine U100 in patients with type 2 diabetes, an industry-funded study found.
Researchers compared the regimens in a 26-week, randomized, double-blind, double-dummy, phase 2 trial in patients who had not previously received long-term insulin treatment and whose type 2 diabetes was inadequately controlled (HbA1c level, 7.0% to 9.5%) while taking metformin with or without a dipeptidyl peptidase-4 inhibitor. The primary end point was change in HbA1c level from baseline to week 26. Safety end points included hypoglycemia and insulin-related adverse events. The study was funded by Novo Nordisk. Results were published Sept. 22 by the New England Journal of Medicine.
Two hundred forty-seven participants were randomly assigned to receive icodec (n=125) or glargine (n=122), at starting doses of 70 U/wk and 10 U/d, respectively. Insulin doses were adjusted weekly to achieve a pre-breakfast patient-measured blood glucose target of 70 to 108 mg/dL (3.89 to 5.99 mmol/L). A pen injector was used for the once-weekly injections, and a vial and syringe were used for the once-daily injections.
Mean HbA1c level at baseline was 8.09% in the icodec group and 7.96% in the glargine group. Estimated mean change from baseline in HbA1c level was −1.33 percentage points in the icodec group and −1.15 percentage points in the glargine group, equating to estimated means of 6.69% and 6.87%, respectively, at week 26. The estimated between-group difference in change from baseline was not significant at −0.18 percentage point (95% CI, –0.38 to 0.02 percentage point, P=0.08).
The rate of level 1 hypoglycemia alerts was 53.6% in the icodec group and 37.7% in the glargine group. Observed rates of hypoglycemia were 5.09 and 2.11 events per patient-year of exposure for the insulins, respectively (estimated rate ratio, 2.42; 95% CI, 1.50 to 3.88). Combined rates of level 2 or level 3 hypoglycemia were low with both types of insulin (16.0% and 9.8%, respectively). Observed event rates were 0.53 and 0.46 event per patient-year of exposure, respectively (estimated rate ratio, 1.09; 95% CI, 0.45 to 2.65). Rates of hypersensitivity and injection-site reactions were low. Most adverse events were mild, and the trial medications were unrelated to all serious events seen in the study.
The study authors said that their trial should be interpreted in the context of its limitations, including that it was not powered to detect significant between-treatment differences for any end point, that insulin adjustment was not tailored by treatment, and that patients treated with sulfonylureas were excluded. They noted that previous studies have found that an injectable once-weekly glucagon-like peptide-1 receptor agonist was associated with significantly better treatment adherence and satisfaction than more frequent dosing.
“Extrapolating these data to our trial results could suggest that once-weekly insulin icodec has the potential to improve treatment satisfaction, adherence, and persistence in patients who are going to receive basal insulin,” the authors wrote. “The smaller number of injections associated with once-weekly icodec than with once-daily basal insulin may facilitate treatment initiation in patients with type 2 diabetes who have not previously taken insulin, by reducing clinical inertia and promoting better acceptance of insulin therapy.”