While insulin continues to represent a foundational treatment for diabetes patients going on a century now, the actual treatment regimen to this day represents a onerous process, requiring repeated jabs and with it a certain social “stigma,” suggests a prominent principal investigator from UT Southwestern Medical Center (UTSWMC). Now a research team led by UTSWMC reports that based on the results of two international randomized controlled trials, a novel injectable insulin treatment that’s only necessary once per week is not only safe but appears to be as effective as a daily regimen of insulin shots. Such an approach could disrupt the diabetes care market and frankly made the type 2 diabetic (T2D) patient’s life easier. That’s because presently those with T2D are subjected to daily insulin injections that pose practical challenges and what some consider questionable results due to influencing factors, such as accuracy of dosages, glycemic targets and timing. What if this novel approach could not only make it easier for T2D patients but also improve overall medication adherence, better glucose control, and raise overall patient quality of life and health? The novo Nordisk insulin 287 (insulin icodec) shows considerable promise but also introduces some risk, at least for some patients, for hypoglycemia. The novel approach now gets put to the bigger, phase 3 clinical trial test via the ONWARDS study program.
The Investigational Treatment
Insulin 287 is under development by Danish pharmaceutical company Novo Nordisk, one of the market’s leading diabetes focused companies and clinical trial sponsors. Novo Nordisk commands about 23% of total diabetes treatment market share. A longer acting basal insulin analogue, insulin 287 is also known as Insulin icodec.
According to some analysts, Novo Nordisk’s Insulin icodec represents the most advanced form of weekly insulin, now progressed to Phase 3 clinical trial. The phase 2 data reported on below does indicate that this drug may represent a useful alternative to daily basal insulin. Some data indicated higher rates of hyperglycemia associated with this experimental regimen, some research suggests that this risk can be mitigated with a more passive titration Schedule. Nonetheless, concerns of hypoglycemia as an issue for some patients, particularly outside of the clinical trial setting remain.
In fact, it’s been reported that some manufacturer concerns about hypoglycemia prevent their entry into this development space.
Recently published in the journal Diabetes Care, the study was led by Dr. Ildiko Lingvay, a professor of internal medicine and population and data sciences at UT Southwestern. Dr. Lingvay is a consultant for the sponsor, Novo Norilsk, and lead author of one of the studies involving 205 patients from seven counties including U.S., Croatia, Germany, Hungary, Poland, Slovakia and Spain.
This particular study consisted of a two-week screening period, 16 weeks of treatment and a five-week follow-up to evaluate three different ways to adjust and optimize the insulin dose and determine which one presented the best balance between effectively lowering glucose while minimizing low-glucose events, reports UT Southwestern Medical Center Newsroom.
The study authors found that based on the results of this study and another study treating people with T2D diabetes with this new, once-a-week injectable insulin called “insulin 287” has proven thus far to be safe and effective as daily injections.
Another study involving 154 participants from five countries (United States, Canada, the Czech Republic, Germany and Italy) followed the same 23-week time frame and evaluated practical aspects of insulin use as well as the best ways to transition from a daily regimen to a new weekly injection regimen. The researchers found that starting with a higher first dose (known as a loading dose) enabled patients to reach their optimal glucose target faster.
Why are these Study Results Important?
Because a daily insulin injection regimen represents a challenge for millions of patients worldwide afflicted with T2D. From the fear of injections to the burden of injectable therapy, this lead to an unfortunate lack of medication adherence that over time places the patient in danger.
Moreover, with the current treatment approach, other risks are constant: the efficacy and safety of ongoing insulin treatment are highly dependent on other elements from dosage accuracy and timing to glycemic targets. UT Southwestern Medical Center went on the record that this novel breakthrough, which would reduce the frequency of treatment administration could lead to better long-term medication adherence, improved glucose control and ultimately better patient well-being.
A Potential ‘Game Changer’
For this new Novo Nordisk treatment (insulin 287) to become approved by regulatory authorities, such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA), the Danish sponsor must now embark on a large phase 3 clinical trial program, which is now ongoing at UT Southwestern and additional trial sites.
Lead investigator Lingvay shared recently that the now ongoing phase 3 clinical trial evaluates the efficacy of the once-weekly insulin treatment in patients with either Type 1 or Type 2 diabetes. Moreover, she noted, “A weekly insulin is a game-changer that will decrease the treatment burden for patients while also improving compliance. This treatment will also decrease the burden on those who care for patients with diabetes requiring insulin. For example, for patients who need help injecting, those living in long-term care facilities, and those with memory problems, a once-weekly insulin will facilitate treatment and decrease the burden on the care providers.”
Phase 3 ONWARDS Program
Novo Nordisk now sponsors a couple studies involving the weekly regimen. In the ONWARDS1 study (NCT04460885), the sponsor and investigational team (including UT Southwestern) compares insulin icodec and insulin glargine in T2D patients who haven’t used insulin previously. While the ONWARDS2 study (NCT04770532) compares insulin icodec (weekly) to insulin Degludec in T2D patients who use daily insulin. In the ONWARDS3 study (NCT04795531), Novo Nordisk sponsors an effort to compare insulin icodec and insulin Degludec in those with T2D who haven’t used insulin before. The ONWARD6 study (NCT04848480) compares the use if insulin icodec (weekly) with insulin Degludec, both in combination with mealtime insulin in T2D patients.
Call to Action: TrialSite will monitor the ONWARDS studies ongoing.