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A novel insulin formulation given once weekly was as safe and effective as a conventional daily insulin product for type 2 diabetes, a randomized, placebo-controlled showed.

Compared with once-daily insulin glargine U100 (Lantus), people treated with once-weekly insulin icodec saw similar mean reductions in HbA1c levels after 26 weeks (between-group difference -0.18%, 95% CI -0.38 to 0.02, P=0.08), reported Julio Rosenstock, MD, of Dallas Diabetes Research Center at Medical City, Dallas, and colleagues.

Simultaneously published in the and presented at the virtual European Association for the Study of Diabetes 2020 meeting, those on the weekly insulin saw an average HbA1c drop of 1.33% versus 1.15% for those on daily insulin glargine.

At the end of 26 weeks, the estimated mean HbA1c level was 6.7% and 6.9% for those on once-weekly and once-daily insulin, respectively.

HbA1c less than 7% was achieved by 72% of the insulin icodec group compared with 68% of those on insulin glargine U100. A target of less than 6.5% was reached by 49% of those on the weekly insulin versus 39% of those on daily insulin.

"There was no statistically significant difference between the two arms, but we did not have the statistical power to document that," Rosenstock said during a virtual presentation of the findings.

"Clearly, patients with type 2 diabetes would prefer fewer injections than current once-daily basal insulin options," he said. "And if we were to have a reduction in the number of injections, this is conceivable that may increase adherence and compliance."

Development of this once-weekly insulin overcame several challenges, Rosenstock said. In comparison to the daily insulins currently available, a weekly formulation had to have a longer half-life, more stable pharmacokinetics and pharmacodynamics, and a slower clearance rate. It would also need to provide similar or improved glycemic control with low risk for hypoglycemic events.

"I think [weekly insulin] would be transformational in the way we manage people with type 2 diabetes requiring insulin," he stated.

The head-to-head, global study included 247 type 2 diabetes patients ages 18 to 75 who had never previously received long-term insulin treatment, and who had inadequate glycemic control (defined as HbA1c from 7% to 9.5%). All participants were taking metformin with or without a DPP-4 inhibitor.

With a double-blind, double-dummy design, half the patients were assigned to insulin icodec at an initial dose of 70 U weekly. Doses were adjusted each week to achieve a pre-breakfast blood glucose between 70 to 108 mg/dL. The other half received insulin glargine at 10 U/day. The insulin icodec group also received daily placebo injections; the insulin glargine control patients received weekly sham injections with the same pen device used for insulin icodec.

Difference in time-in-target-range for blood glucose (70 to 140 mg/dL) was 5.4 percentage points in favor of insulin icodec (95% CI 0.7-10.1, P=0.02), corresponding to about 78 minutes longer per day.

Rates of hypoglycemia were low in both groups. Those on insulin icodec had 0.53 hypoglycemic events per patient-year versus 0.46 events among those on insulin glargine. These events included hypoglycemia rated with a severity level of 2 -- blood glucose below 54 mg/dL -- or severity level 3, which could lead to severe cognitive impairment. Only one episode at level 3 was reported among those on insulin icodec, while none occurred in the insulin glargine group.

Other adverse events did not differ between the weekly and daily insulins.

During the last two weeks of treatment, those on the weekly insulin averaged about 229 units per week of insulin. This equated to about 33 units per day versus about 41 units per day for those on insulin glargine U100.

"Based on the robustness of these data, further evidence of the role of weekly basal insulin icodec will be investigated in a comprehensive phase III clinical development program that is about to start," Rosenstock concluded.

Insulin icodec developer to begin the phase III program later this year.

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