Called “transformational” by its lead investigator, a new weekly basal insulin cleared a major hurdle by posting positive results in a phase 2 trial, lowering glucose just as safely and effectively as traditional 24-hour insulin injections.
Pharmaceutical companies have been working on a weekly basal insulin for more than a decade, but the recent release of trial results by Novo Nordisk suddenly brings the concept into much greater focus. Novo Nordisk’s new product is named “icodec” insulin, a long-acting basal insulin analogue with a half-life of 196 hours (a touch over 8 days). Insulin icodec binds to albumin, a protein found in the bloodstream, which allows for a slow and steady glucose-lowering effect.
The trial results were announced at the ADA’s Scientific Sessions conference, and were the highlight of a symposium on the topic of weekly insulins. The study took 247 adults with Type 2 diabetes that had not been able to adequately lower their blood glucose levels through the use of non-insulin medication. Half were put on a traditional regimen of once-daily injections of a standard 24-hour basal insulin, and the other half used the experimental weekly insulin. At the end of the study, those using the weekly insulin injections had achieved results that were at least as good as those using the daily insulin according to several glycemic benchmarks. Importantly, the rate of serious hypoglycemic events did not increase for those using weekly insulin.
One of the promising details of the study was that the weekly injection group actually used significantly less insulin in order to achieve those equally good blood sugar numbers. Many experts are beginning to agree that the use of insulin to treat T2D is highly problematic.
Dr. Julio Rosenstock, who led the study, was ebullient: “My feeling – totally biased – is that this insulin, if proven efficacious … is going to be transformational in the management of Type 2 diabetes.”
Perhaps the most important appeal of the new weekly insulin for patients with T2D is the promised ease of use. Many people with diabetes do struggle to accept insulin injections initially, or fail to keep up with them, for a variety of reasons. Among them are some barriers that are likely to be assuaged by a once-weekly injection, such as a fear of needles. Although as of yet there has been no specific study of this question, it seems safe to assume, as Dr. Home did, that a weekly insulin injection is “likely to be a popular option for starting insulin therapy.” Dr. Rosenstock, who led the Novo Nordisk trial, stated “I don’t think that you have to have a sophisticated study to demonstrate that it will improve patient acceptance. I mean, people will prefer one injection as opposed to seven injections.”
A single weekly injection is likely to become a reality for patients with Type 2 diabetes before it’s an option for those with Type 1. As Professor Philip Home of Newcastle University explained during the symposium, some of the potential issues with a weekly injection – particularly the reduced ability to respond to short-term changes in insulin needs when triggered (predictably or unpredictably) by erratic insulin absorption, illness, exercise, alcohol use or other factors – are likely to be more problematic in the setting of T1D.
Imagine taking your weekly basal shot only to find that some known or unknown circumstance has greatly increased your insulin sensitivity for the week – you’d be fighting off hypoglycemia for up to seven days, a potential danger. Conversely, if you needed to increase basal insulin rates due to illness, you couldn’t easily do it without using a second faster-acting “rescue” basal insulin. Therefore, for patients that already fine-tune their basal insulin day-by-day or even minute-by-minute (with an insulin pump), a weekly insulin injection is likely to represent a step backwards in glycemic control. In summary, Dr. Home suggested that weekly insulin would be “unsuitable” for most patients with Type 1 diabetes. Nevertheless, both Novo Nordisk and Eli Lilly are pursuing clinical trials of weekly insulin with Type 1 patients, the progress of which certainly bear watching.
Dr. Rosenstock promised to unveil the results of two additional studies at the annual meeting of the EASD in September. If one can judge from Dr. Rosenstock’s cheery demeanor when he made that statement, the results of those studies are also likely to be encouraging. Next up is a phase 3 trial for users with Type 2 diabetes, which Novo Nordisk promised would get underway in 2020. This type of study is typically larger and longer than phase 2, and should be able to look more carefully at the safety of the drug. Several open questions do remain: does the drug negatively impact insulin sensitivity? Is there a risk of cancer or other major side effects?
Dr. Stefano Del Prato of the University of Pisa presented the results of the Novo Nordisk trial during the symposium. Recognizing that many phase 3 trials tend to have a high failure rate, Dr. Del Prato concluded, “This seems to be an interesting, maybe promising avenue, but to my eyes, this is the beginning of the story, and we still have a long way to go.”