The race to develop a smart insulin that actually reacts to changing blood sugars has heated up once again, with two big players now contributing millions towards creating this glucose-responsive insulin that could relieve us PWDs of all the calculation, guesswork, and correcting required when our sugars spike. Wow!

Sanofi and JDRFOn Feb. 25, news broke that to provide as much as $4.6 million toward research projects aimed at creating smart insulin. The collaborative group reviewed more than a dozen applications for R&D focused on this, and four were chosen to receive the funding over the next three years:

  • Dr. Danny Chou, assistant professor of biochemistry at the University of Utah, who's been developing an insulin formulation that has a biochemical trigger or "switch" that only works when it's activated by glucose in the system. This has been tested on diabetic mice, delivered by syringe and dermal adhesive strip. (More info at this .)
  • Dr. Alborz Mahdavi, a chemical and biomolecular engineer who founded California-based that's focused on using "bio-inspired" approaches to allow blood sugar levels to be sensed and used to activate a smart insulin. Basically, as we've heard Dr. Mahdavi describe it, his approach is similar to a light switch that can be turned on and off.
  • Dr. Christoph Hagemeyer, a nanobiotechnology professor from Monash University in Australia, whose work in diabetes and heart health has involved targeted delivery of medications and molecular imaging. In developing a smart insulin, his team is creating nanoparticles to produce the insulin’s glucose-sensing effect.
  • Dr. Zhen Gu, a biomedical engineer and professor at North Carolina State/UNC, who's developing a microneedle for delivering glucose-responsive insulin. His research has also evolved more recently into testing this patch design tech , which could deliver glucose responsive insulin in much the same way.

Needless to say, we're excited to hear how these projects develop!

Setting Smart Insulin Expectations

A year ago, there was a wave of excitement about smart insulin over research led by Dr. Matthew Webber at MIT and Dr. Danny Chou in Utah. But then not much more materialized over the course of the past year... until now, when Dr. Chou's work becomes part of this four-project announcement.

So how soon will we actually see insulin with brains of its own, that can detect blood sugar levels and automatically dose just the right amount?

Smart Insulin “People get excited about smart insulin, but we have to set the proper expectations as to timeframes up front. These are super-early projects that are going to take time to mature. These are not going to come tomorrow and we can’t overpromise, but hopefully they’ll go as fast as they can,” says Aaron Kowalski, Chief Mission Officer of JDRF who's a longtime type 1 himself.

Kowalski admits that many in the D-Size now were disappointed following the news of SmartCells being developed and then , but then seemingly falling off the radar since. Yes progress is underway, he says.

Merck's SmartCells

In 2010, that makes it possible to "auto-regulate the release of a therapeutic based on the plasma concentration of a designated molecular indicator," with high hopes for insulin that would release "only in the presence of a specific glucose concentration range."

Then they went dark on this issue for about four years, until an investor briefing in May 2014 in which Merck made mention of working on an investigational smart insulin (dubbed in the research), saying they were ready to move forward into Phase I human trials. But there wasn't much more detail provided other than an ETA for those human trials to begin by the end of 2014.

The U.S. clinical trial database shows that Merck's did begin in November 2014 and actually wraps up this month, in March 2016. Merck’s smart insulin is apparently now being referred to as .

We understand that a big concern here was that you'd have this novel, smart insulin hovering around in a person's body -- potentially a problem if someone didn't eat or engaged in some intense BG-lowering exercise. That posed risk of the smart insulin causing dangerous hypoglycemia.

But Merck research showed that's being addressed, Kowalski says. "A Merck slide from (2015) shows this has a lot more safety features built in than the original SmartCells approach, of injecting insulin where it didn't work but didn't stick to cells, and no one understood if it would react or stay in the body if it wasn't active."

Now, it seems clear that patients could inject this smart insulin once or twice a day without the risk of going low since the substance doesn't last for a full 24 hours. Or they could use it in an insulin pump with a low basal rate of glucose- responsive insulin, just enough for it to be present in the body to react to a glucose spike if needed.

What this Merck project is doing is teaching researchers more about the potential for further R&D in glucose-responsive insulin -- especially as it relates to the delivery devices being designed, Kowalski says.

Smart Insulin Delivery Tech

In fact, what's most interesting about this latest JDRF-Sanofi news is that the delivery technology is more of a focus than ever before. Instead of just injecting the stuff, we may finally see some realization of the "non-invasive dream."

Dr. Chou's is working on a smart insulin adhesive patch containing 121 microneedles loaded with specialized nanoparticles containing an enzyme called glucose oxidase. According to , "when glucose levels reach a critical level, the glucose oxidase begins consuming oxygen, creating a hypoxic local environment around the Smart Insulin patchnanoparticles. This then triggers the 2-nitroimidazole to become hydrophilic, altering the nanoparticles’ conformation in a way that releases the insulin within."

Dr. Hagemeyer is creating nano-particles capable of delivering responsive insulin -- presumably also via a tiny, non-invasive patch of sorts. (The quite complicated science behind this is .)

But our eyes turned most toward the work Dr. Gu in North Carolina is doing on a rather advanced . He's developing a thin, square patch no bigger than a penny that would be covered with more than 100 teeny tiny needles, each the size of an eyelash. These so-called microneedles are packed with microscopic storage units for insulin and glucose-sensing enzymes that rapidly release that when glucose gets too high.

Data published in 2015 from a mouse study (of course) shows the patch could lower mice glucose levels for up to 9 hours, and once the research gets into human trials the patch would be personalized to account for each PWD's weight and insulin sensitivity. A pretty neat concept!

More recently, we also hear this same design with actual beta cells, which wouldn't have to deliver smart insulin but could produce real insulin in much the same way.

Overall, progress is great to see and we're happy that continued efforts are happening on this smart insulin front.

It's easy to excited about announcements and news headlines, but the real trick is staying excited over time when the discussion dims. Here's to hoping we hear semi-regular updates on these above projects, and they don't get swept under the rug even if they don't work out as we all hope.