On the Horizon – a Weekly Insulin, Oral Insulin, Smart Insulin, and Biosimilars
By Matthew Garza
Insulin has come a long way since its discovery over 100 years ago. Learn what new insulin options may be on the horizon that could revolutionize the way diabetes is managed.
In 2021, the world celebrated 100 years of insulin. Over those 100 years, insulin has revolutionized diabetes treatment, turning type 1 diabetes from a terminal disease to a chronic condition. Life expectancy has been extended and quality of life has been improved for millions of people living with diabetes. In the last few decades, impressive advancements have enabled insulin formulations to become better and better, giving rise to inhaled insulin, rapid- and ultra-rapid-acting insulins, and long-acting insulins.
But now, we are on the cusp of even more impressive advancements. At the 82nd ADA Scientific Sessions, four experts presented the latest updates and where we are in the field of insulin innovations: once-weekly insulin, oral insulin, smart insulin, and biosimilars.
There are great potential benefits of a once-weekly insulin option – fewer injections for people with diabetes, a better chance that people maintain their medication regimen, and even the potential for addressing clinical inertia. And we may be closer to having a once-weekly insulin option than many would think.
On day four of the American Diabetes Association 82nd annual Scientific Sessions, Dr. Harpreet Bajaj, endocrinologist and director of late-phase research at LMC Healthcare in Toronto, discussed the two once-weekly insulins currently in Phase 3 clinical trials, termed Basal Insulin Fc (BIF) and Insulin Icodec.
The BIF phase 3 clinical trial program includes plans for five studies called the QWINT studies. The studies will compare BIF to insulin glargine (Lantus) and insulin degludec (Tresiba) primarily in people with type 2 diabetes; the QWINT 5 trial will compare BIF to insulin degludec in people with type 1. In results from the phase 2 trials of this once-weekly insulin, BIF was shown to be similar to degludec for reducing A1C, with a similar risk for hypoglycemia.
The insulin icodec phase 3 clinical trial program includes six studies called the ONWARDS studies. Similar to the studies of BIF, ONWARDS compares icodec to insulin glargine and insulin degludec, primarily in people with type 2 diabetes, although ONWARDS 6 includes people with type 1 diabetes.
Preliminary data from ONWARDS 1, 2, and 6 shows:
In people with type 2 diabetes, once weekly insulin icodec was superior to once daily degludec with an average A1C reduction of 0.93 percentage points over 26 weeks, compared to 0.71 percentage points with degludec.
Insulin icodec was superior to glargine in people with type 2, with an average A1C reduction of 1.55 percentage points over 52 weeks compared to 1.35 a percentage point reduction with glargine.
Rates of severe hypoglycemia were statistically the same between icodec and glargine in people with type 2.
In people with type 1 diabetes, Insulin icodec was similar to degludec, with an average A1C reduction of 0.47 percentage points over 26 weeks, compared to 0.51 percentage points for degludec.
Rates of severe hypoglycemia were significantly higher in the icodec group than in the degludec group in people with type 1.
What is the real impact of a once-weekly insulin? “Not having to take a daily injection feels like a vacation for the last 6 months of the trial,” said one participant.
Bajaj added, “Let’s hope we can make the vacation longer.”
Dr. George Grunberger, clinical professor, Internal Medicine and Molecular Medicine and Genetics at Wayne State University School of Medicine and chairman of Grunberger Diabetes Institute, spoke to the possibility of oral insulin options in his presentation.
Oral insulins have not been successful thus far because, as he said, “Mother Nature does not want the GI tract [gut] to absorb large molecules,” like insulin.
Despite this challenge, however, a few emerging options may finally address this. These include:
Oral nanoparticles – specially designed pills that can overcome the challenges of delivering insulin orally
Oral insulin delivery systems – think of this as a pill that is actually a little device which lands in your gut and delivers insulin through a microscopic needle injection
Insulin pill – this is currently being studied in clinical trials by the company Oramed
It’s too early to tell if any of these options will be successful, but early data from Oramed trials suggest that we may soon have more information about whether their insulin pill will work.
The development of smart insulin options means designing an insulin that responds to glucose levels – working when blood glucose rises and turning off when it falls. Dr. Michael Weiss, distinguished professor at the Indiana University School of Medicine, explained the potential ways that a glucose responsive insulin could work. Ideally, the goal of such an insulin would be to reduce the risk for hypoglycemia, stabilize and keep glucose levels in range, and improve quality of life.
Though we are still years away from smart insulins making their way into clinical trials, early computer simulation models have helped researchers. Only time will tell if the technology can be translated from simulations into actual human trials.
Biosimilar Insulin and Affordability
Shifting slightly from the technical aspects of these other insulin innovations, Dr. Rita Rastogi Kalyani, editor-in-chief of Johns Hopkins Diabetes Guide and associate professor of Medicine, spoke about biosimilar insulins and the ways they could impact insulin affordability.
When an insulin is “biosimilar,” it means that it is highly similar to a reference product, with no clinically meaningful difference in purity, potency, or safety. To learn more about what biosimilars are and which are available in the US, read: “What are Biosimilars?”
Kalyani presented research showing that in the past five years, insulin glargine accounted for over half of insulin prescriptions in the US. Given that we now have a biosimilar insulin (Semglee) that is interchangeable with insulin glargine (Lantus), she highlighted that biosimilars could deliver a 65% discount or more if there were enough available biosimilar insulins on the market.