Trying to calculate your insulin doses for injections, without the help of a digital "wizard" for doing the math automatically? There's an app for that! (of course).

Apps for so-called "insulin titration" have been around since roughly 2010, when the first basic dose calculators like RapidCalc hit the market. Next came the first FDA regulatory approval for a "mobile prescription therapy aid" with WellDoc's BlueStar app in 2013, followed more recently by apps from both big pharma and small startups. Some are specific to basal (long-acting) insulin, or even to specific insulin brands.

Just last week, the little known Detroit-based startup Hygieia, Inc. snagged FDA approval for a new offering: the first-ever mobile titration app cleared for all type 2 insulin regimens, including both long-acting (basal) and mealtime (bolus) insulin. It's also the first insulin titration app that can connect to any glucose meter (or in theory, continuous glucose monitor system) that shares data with the cloud.

While there have been a lot of headlines on this new app, none of the publications we've seen have really explained what Hygieia is all about, or how the technology actually works. That's where we come in.

In what they call their "d-Nav Insulin Guidance Service," users’ individual blood glucose data is beamed to a cloud-based service that uses an algorithm, along with input from their clinic and healthcare provider, to send them insulin dosing recommendations through the app (available for both iOS and Android phones).

They tell us to think of it like a nav system for your car.

"Like a GPS, you tell the device where you want to go, and it creates a master plan and then adjusts the plan to your current blood sugar levels. The benefit of a GPS isn't knowing where you are, it's knowing what to do next. We don't see a value in glucose readings per se, but rather in what you do with the numbers," says Hygieia co-founder Dr. Eran Bashan.

published in The Lancet medical journal late last week show a significant decrease in A1C in the group using the d-Nav system, versus those relying on their doctor's support alone. And to top it off, d-Nav is being supported  by a Michigan insurer in a way that's unique in the scope of insulin titration apps.

 

So What Exactly is d-Nav?

You may remember from our previous coverage that the first iteration of d-Nav was a device actually modeled after a Blackberry. It looks like a cross between an insulin pump and a small Etch-a-Sketch.

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In fact, it served as a glucometer that used proprietary test strips to check blood sugar but flashed the BG result for just three seconds before the number would vanish. Then, using pre-programmed settings by a physician and taking IOB (insulin on board) into account, the device would calculate a correction dose or food bolus (if needed).

For the most part, that remains the form factor. Except now, Hygieia has added in a mobile app functionality directly on a smartphone and the extra clunky device is optional. You can choose to use the d-Nav device to take your fingersticks, or BG results can simply be shared wirelessly from any cloud-connected fingerstick meter.

For someone on two shots a day, for example, the d-Nav app displays any correction bolus that might be needed based on the time of day and its pre-programmed knowledge of when their last insulin injection was taken. The IOB is calculated based on the user's set insulin regime. People on basal-bolus injections multiple times a day can plug in their carbohydrate counts and the app calculates a recommended total insulin dose.

The user can of course decide to follow or ignore the recommendation — just like any driver can rely on GPS navigation behind the wheel or choose to go another route.

The service is aimed at the growing population of type 2 PWDs (people with diabetes) who use insulin, although it is of course just as beneficial to any type 1 who isn't using an insulin pump.

To be clear, this isn't something you can just download from the iOS or Google Play Store; you must go through a doctor, and availability is currently limited to one specific clinic in Southeast Michigan, where patients can get a prescription for the d-Nav and are guided on it from there.

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The big deal is that d-Nav goes much further than other insulin titration apps by analyzing glucose patterns and helping users make frequent adjustments -- and if it succeeds in Michigan, we expect to see this tool popping up in clinics around the country.

 

Higee-what?

The company name may seem odd, but it's pronounced "hy-jee-uh" and hails from the 1st century Greek goddess of health, daughter of the God of Medicine. It also brings to mind the Bowl of Hygieia, one of the universal symbols of pharmacy.

We introduced Hygieia here at the 'Mine back in 2011 in connection with our DiabetesMine Design Challenge. But the company has mostly been under the radar in recent years, even after receiving European regulatory OK in late 2012 to launch their product overseas.

Hygieia's co-founders Dr. Eran Bashan and Dr. Israel Hodish are both Israeli natives who came to the University of Michigan's engineering school in 2004. Hodish is an endocrinologist at U-M's Medical School who serves as the startup's clinical advisor. Bashan came from a military leadership role before working in engineering management developing consumer electronics, while Hodish had an interest in both engineering and gene therapy that led him to endocrinology.

They got the idea for a "diabetes GPS" back in 2008. They apparently met for dinner one night on campus and began discussing the need for some kind of technology to help take the insulin calculation guesswork out of D-management. They fleshed out a plan, and launched their company in August of that year -- just two weeks before the collapse of financial giant Lehman Brothers. Neither had a personal diabetes connection, but both say that over the years family members developed diabetes and have begun injecting insulin.

With the flawed U.S. healthcare system pushing more and more patients to general practitioners instead of more expensive specialists, the need for this type of direct patient assistance is critical, they say.

"We are seeing more people with type 2... going on insulin. You need constant adjustments, and being engaged is a lot of work. Our system allows patients to adjust their insulin immediately based on what's happening in their body, rather than wait up to 90 days to see a physician and then change their dosage," Bashan says.

 

The Insulin Titration App Landscape

Bashan and Hodish are certainly not the only experts who've identified this need. As noted, there's a growing field of mobile apps geared toward insulin dosing:

  • RapidCalc for basal-bolus regimen, with "intelligent tracking" of insulin on board and detailed tracking features
  • The PredictBGL insulin dose calculator app out of Australia
  • The iSage app from AmalgamRx, which in 2017 became the first app to be FDA approved for use with all brands of basal (long-acting) insulin
  • Glytec's FDA-cleared Glucommander app that sends dose adjustment recommendations for both basal and bolus insulin to healthcare providers, who approve the changes and forward them to users (now available through the Livongo diabetes management service)
  • Eli Lilly's Go Dose app aimed at titrating its own Humalog brand insulin was approved in early 2017, but Lilly Diabetes tells us they opted to not launch the mobile app after deciding to instead focus on its broader connected device landscape.

The Hygieia founders emphasize that their new app is uniquely useful for any injectable insulin a PWD might take -- covering both basal adjustments and bolusing for food or corrections.

And their presented at the big Advanced Technologies and Treatments for Diabetes (ATTD) conference in Berlin last week shows that it works; in a multi-site, randomized controlled study at three national diabetes centers over the course of 6 months, 181 study participants saw significant A1C reductions and overall fewer hypoglycemia episodes.

Does Hygieia's plan change as continuous glucose monitors (CGMs) become more widely used? Not really, Bashan says. They could develop a future business-to-business partnership allowing CGM data to be weaved into the d-Nav platform, but Bashan doesn't see it likely that CGM will become widely prescribed to T2s any time soon. That's why he doesn't expect the red d-Nav device itself to be phased out, because fingersticks will remain a mainstay for so many in the T2 insulin-using world, and lots of those patients won't have access to a cloud-connected meter.

What makes Hygieia even more interesting is their access model: they've managed to get an insurance carrier to cover all of the needed strips and d-Nav supplies for free from the clinic, on the insurer's dime.

 

As Always, Insurance Coverage is Key

Interestingly, Hygieia not only develops technology, but is in the business of setting up specialty clinics focused on T2 diabetes medication optimization. These clinics are staffed by primary care physicians, who work with patients to optimize their dosage of insulin, GLP-1 meds, and oral medications for lowering glucose.

Currently, they have just one local clinic up and running in the Metro Detroit area, but the company expects to open four additional clinics in Southeast Michigan before long, and expand from there.

While Hygieia's d-Nav is being employed there, these clinics are "medication and tool agnostic," Bashan tells us. "They work like Dialysis Centers, where patients go in for a very specific purpose. We're not replacing the endocrinologist or other aspects of broader diabetes care."

In mid-2018, the Michigan-based company contracted with Blue Cross Blue Shield of Michigan (BCBSM) to support these clinics, and employ Hygieia's d-Nav for insulin-using T2 PWDs on PPO and its Blue Care Network HMO plans. That followed a year-long pilot study by BCBSM, in which 200 PWDs using d-Nav achieved improved clinical outcomes and lower overall healthcare costs -- $6,000 per patient per year, to a pharmacy savings of more than $1,700 across all patients, Hygieia tells us.

Wow!

With this latest contract, they're moving through Southeast Michigan and into the west side of the state, where estimated thousands of BCBSM members will use the Hygieia service, and beyond. That's the way to get traction in the market: negotiate for pilot studies that illustrate the value of your tools or service -- thereby motivating payers to cover it broadly.

As of now, Hygieia has no plans to offer diabetes coaching -- nutrition, exercise or otherwise -- but rather is focused solely on precise insulin dosing and injection-related support, such as optimizing injection sites and insulin pen use.

 

A Little Help Goes a Long Way

Clearly, insulin titration apps can add a lot of value (anything's better than blind dosing, no?), and we're excited that new algorithms will eventually pair this capability with CGMs -- especially as Dexcom moves in that direction with its G6 and later products, and the mobile app updates it has planned in the next year or two.

The idea of a GPS for insulin dosing reminds us quite a bit of the original discussions around CGM when it came out (a new guidance system!), and we predict it's only a matter of time before these titration tools become a new Standard of Care for those not connected to an insulin pump or closed loop that auto-doses insulin.