Once-weekly insulin efficacy similar to daily therapy in type 2 diabetes
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Adults with type 2 diabetes assigned an investigational once-weekly insulin therapy experienced a decrease in HbA1c similar to that seen with daily insulin glargine, according to findings from a phase 2 randomized controlled trial.
“Clinical inertia is highly prevalent in the management of type 2 diabetes, with the longest delays reported for insulin initiation,” Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas, and colleagues wrote in a study published in The New England Journal of Medicine. “Previous data have indicated that patients with type 2 diabetes would generally prefer fewer injections and greater flexibility than is typical of the current once-daily treatment options. Therefore, reducing the number of injections could potentially increase acceptance of an adherence to insulin treatment among patients with type 2 diabetes, thereby potentially improving glycemic control.”
Rosenstock and colleagues analyzed data from 247 adults with type 2 diabetes with an HbA1c between 7% and 9.5% while prescribed metformin with or without a DPP-IV inhibitor. Researchers randomly assigned participants to once-weekly insulin icodec (Novo Nordisk; mean baseline HbA1c, 8.09%; 56% men; mean age, 60 years) plus once-daily placebo or to insulin glargine (Lantus, Sanofi; mean baseline HbA1c, 7.96%; 56.6% men; mean age, 60 years) plus once-daily placebo. Starting dose of insulin icodec was 70 U once weekly; starting dose of insulin glargine was 10 U once daily. Insulin doses were adjusted weekly to achieve a pre-breakfast patient-measured blood glucose target of 70 mg/dL to 180 mg/dL. Primary endpoint was change in HbA1c from baseline to 26 weeks.
At 26 weeks, estimated mean change from baseline HbA1c was –1.33 percentage points in the weekly insulin group and –1.15 in the insulin glargine group, to estimated means of 6.69% and 6.87%, respectively. Estimated between-group difference in change from baseline HbA1c was –0.18 percentage points (95% CI, –0.38 to 0.02).
Observed rates of level 2 hypoglycemia (below 54 mg/dL ) or level 3 hypoglycemia (severe cognitive impairment) were low in the weekly insulin and glargine groups, with rates of 0.53 events per patient year and 0.46 events per patient year, respectively, for an estimated rate ratio of 1.09 (95% CI, 0.45-2.65). There were no between-group differences in insulin-related key adverse events. No serious events were deemed related to the trial therapies.
Researchers cautioned that the findings should be interpreted in the context of several limitations. The trial was not powered to detect significant differences between treatments for any endpoint; however, these data suggest that such a trial design may be “worth exploring in the future,” the researchers wrote.
“In addition, the double-blind, double-dummy design and the requirement to use a treat-to-target approach in regulatory trials necessitated an identical dose-adjustment frequency for both treatments, which meant that insulin adjustment was not tailored for each treatment,” the researchers wrote, adding that “further investigation will be needed in a larger and more diverse patient population to evaluate the hypoglycemic profile of icodec.”
In an online presentation during the virtual European Association for the Study of Diabetes Annual Meeting, Rosenstock said researchers plan to initiate a phase 3 study of weekly insulin in adults with type 2 diabetes.
“In my judgment, insulin icodec could potentially improve treatment acceptance and likely would facilitate management in type 2 diabetes patients needing basal insulin, and I think it will be transformational in the way we manage people with type 2 diabetes requiring insulin,” he said.
In a live question and answer session following his presentation, Rosenstock said newly diagnosed adults could derive benefit from weekly insulin.
“For sure, this will benefit people who are starting insulin therapy,” Rosenstick said. “This will facilitate and increase acceptance and reduce clinical inertia. It would be much easier to convince [patients] to take one injection per week as opposed to one injection per day. We are talking 52 injections per year instead of 365 injections per year. For people already on basal insulin, we have shown today that they can be switched to weekly therapy.”
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Susan Cornell, PharmD, CDE, FAPhA, FAADE
The data is exciting. Once-weekly insulin will improve adherence to insulin for many patients with type 2 diabetes. The study mentions the benefits of a once-weekly GLP-1 receptor agonist, and the same may apply here. Additionally, there is future potential to combine weekly insulin with a weekly GLP-1 receptor agonist, drastically reducing the injection burden. The authors put this in context, noting that instead of 365 injections per year, a person would only have 52 injections per year.
Weekly insulin is released at a slower rate vs. daily insulin, similar to profile of long-acting insulin degludec injection (Tresiba, Novo Nordisk) or long-acting insulin glargine injection (Toujeo, Sanofi). The hesitation by some when they hear once-weekly insulin is usually due to concern about hypoglycemia. How do you actively treat hypoglycemia when prescribed a long-acting insulin? With the long-acting daily insulins, hypoglycemia has not been an issue. From a pharmacokinetic standpoint, the hypothesis is the release is so slow that you get this nice, flat line coverage. As long as a person is eating appropriately, they will be fine.
My biggest takeaway was the authors’ use of time-in-range using Freestyle Libre continuous glucose monitor (Abbott) for this study. Time-in-range will be important going forward. An HbA1c does not tell you the glucose fluctuation; however, an HbA1c of 7% with a time-in-range of 70% tells you a lot.
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Rosenstock J. Once-weekly basal insulin icodec offers comparable efficacy and safety vs. once-daily insulin glargine U100 in insulin naïve patients with type 2 diabetes inadequately controls on OADs. Presented at: EASD Annual Meeting; Sept. 21-25, 2020 (virtual meeting).
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