Dexcom G6 Accuracy vs. iCGM Special Controls


#1

From Close Concerns Diabetes Technology Meeting Highlights

Revealed: Dexcom G6 Accuracy vs. iCGM Special Controls (high bar indeed); G6 Enhancements for 14-Day Wear, 1-hr Warmup, New Adhesive, Less Lag; Vagueness on Verily; TypeZero Next-Gen Algorithm Work

Dexcom VP Mr. Peter Simpson shared a number of never-before-seen slides, including G6’s accuracy stacked up against the iCGM special controls and data on next-gen enhancements to G6: 14-day wear and 1-hour warmup (still sub-10% MARD, >90% of points within 20/20), a new adhesive that propels ~90% of sensors lasting 14 days (up from ~75% now), and reduced time lag down to 2.5 minutes vs. YSI (currently ~4 minutes). Vagueness on the fully disposable Verily sensor continues, with just a side profile picture shown this time around without any scale comparator – less detail than we got two years ago at DTM, and it remains unclear if two Verily generations will launch. We also heard about new TypeZero/Dexcom work on a next-gen closed-loop algorithm, which will enable simplified/no meal announcement, a more aggressive and personalized algorithm to optimize time-in-range, and a simplified system startup. Dexcom and TypeZero are also joining forces on MDI decision support, including a trend-based bolus calculator and more dosing guidance. Many slides and details are enclosed below!

  • For the first time since G6 launched, we got to see the sensor’s accuracy stacked up against the iCGM special controls – 95% lower confidence bound finally included for all glucose bins. The G6 label does not actually share the confidence intervals around the point estimates, so this was a long-needed slide. The takeaway remains the same, as Mr. Simpson noted: “FDA has set a very high bar for accuracy.” However, it’s now even clearer just how high that bar is, since G6 barely crosses the thresholds in some areas. (One could more easily argue now that these controls were designed around G6, and like any line drawn in the sand, there is some arbitrariness here – e.g., why “87%” and not “86%” for within 20%?) This slide also reminds us that using the lower bound of the 95% confidence interval raises the bar even higher, since it requires: (i) a point estimate that exceeds the threshold by a meaningful margin; or (ii) a study large enough that the confidence interval is closely aligned to the point accuracy. All in all, it’s clear that Abbott and Medtronic are not likely to obtain iCGM accuracy standards unless they can make leaps forward in sensor accuracy. Senseonics may meet the bar with Eversense, though it is prioritizing 180-day wear first.

  • Mr. Simpson also shared brand-new G6 platform enhancement data, starting with an n=78 trial of 1-hour startup and 14-day wear. The data look quite good, with MARD still under 10% – including between hour 1-2 – and 91.9%-93.7% of points within 20% of 20 mg/dl. Only data from hours 1-2, day 10, and day 14 were presented, so we’re not sure what the aggregate performance looks like. Adam asked in Q&A about whether this data meets the iCGM standard, and Mr. Simpson clarified that the study was not powered to adequately answer that question; indeed, far more patients/paired points would be needed to get tight enough confidence intervals, especially with the above in mind. Dexcom’s 3Q18 call had not confirmed this trial’s completion, which clearly occurred well within the original plans for “2H18.” CEO Kevin Sayer said Dexcom will first get its new adhesive (see below) ready before moving to 14-day wear, so this enhancement sounds like a mid/late-2019 launch at the earliest – assuming a larger trial confirms 14-day/1-hour G6 still meets the iCGM accuracy benchmarks. For context, G6 currently has an overall MARD of 9.0% and overall 94% of points within 20/20, with a day 1 MARD of 9.3% and 91.1% within 20/20; the below looks right on par.

  • In our view, this is among the most important enhancements to G6, since it would match FreeStyle Libre’s updated wear/warmup time. (Libre 14-day launched in late October in the US following FDA approval in July.) Plus, a 14-day wear G6 would give Dexcom more pricing cushion and better margins, reducing sensors from three down to two per month.

  • Mr. Simpson also showed new data (n=24) from a “high reliability patch” for G6, which prompts an ~20% relative increase in 14-day sensor survival vs. the current adhesive – per the graph below, ~75% of current G6 patches survive to 14 days, which increases to ~90% with the next-gen adhesive. No further details or timing were shared, though this seems like an excellent and necessary upgrade. On the 3Q18 call, CEO Kevin Sayer shared that this new G6 adhesive is coming out in the “not-too-distant future.” We’d guess sometime in 2019 at this stage, though it was not specified. The size of the patch skirt looks unchanged, so presumably this changes the stickiness or materials. We’re not sure if this patch will reduce skin reactions, which can prevent some from using CGM. On Thursday at DTM, 3M noted the hard tradeoffs that come with adhesive, since improving on one dimension (stickiness) often comes at the expense of others (irritation).

  • Dexcom is also working on further reducing G6’s sensor time lag vs. YSI, which is ~4 minutes now and ~2.5 minutes with the next-gen version. The data was marked as unpublished and For context, the G4 platinum had a 6.5 minute lag, G4 with software 505 brought it down to 5.7 minutes, and G5 brought it down to 5 minutes. In Q&A, a comment noted that even if the current G6 lag was zero, it could still be up to five minutes (maximum) since readings only display in five-minute intervals; reducing updates to every minute would help the user experience on the lag front. Of course, that would also demand more battery life to relay Bluetooth reading, so the tradeoff is not quite that simple!

  • Regarding the next-gen disposable CGM with Verily, Dexcom is “not quite ready to show the final design,” but Mr. Simpson did show a profile of the very thin wearable. It looks quite slim, as expected, but there was no size comparator, making it hard to know just how thin it is (e.g., is it the originally planned penny-sized thickness?). This was the only Verily device shown, and it was unclear if this was the first- or second-gen version; we assume the latter, which has the low-cost advantage, the next-gen sensor, and is still under development. As of Dexcom’s 3Q18 call, the company was “considering options” for the gen one Verily device (using current G6), and the smaller, low-cost, second-gen device was slated for “late 2020/early 2021.” Dexcom’s upcoming investor day on December 4 should hopefully give more specifics on the Verily plans.

  • Citing the acquisition of TypeZero, Mr. Simpson noted the team is already working on a next-gen closed loop algorithm with “full automation” (no meal announcement!), simplified startup and meal announcements, optimization to increase time-in-range, and personalized delivery based on a patient’s data signature. Seeing both “meal announcement” and “no meal announcement” implied to us that the system will integrate manual meal announcement when a user does so, though it will be able to cope without it – perhaps via more aggressive automated correction boluses. The first-gen version of this algorithm is in its pivotal trial within Tandem’s Control-IQ system, slated for a summer 2019 launch.

  • TypeZero/Dexcom continue to work on better tools for MDI users, including a trend-adjusted bolus calculator, actionable insights, smart pen integration, and both real-time and retrospective therapy guidance. No timing was shared in this talk. The 3Q18 call said pilots of this technology are ongoing, with a broader commercial rollout “certainly by 2020.” Dr. Marc Breton’s talk on Day #2 gave a great overview of the technology, which is leaps better than the guidance MDI users have now.

#2

Nice to see the data and knowing Dexcom is working on better algorithms and sets,


#3

That’s a scary thought–receiving just TWO sensors per month. FIRST of all, I’m on Medicare-provided G5’s now and I do NOT get them every “month”, or every 30 days, because orders are not processed until 30 days has elapsed from the LAST SHIPMENT. I’ve had shipments delayed for 5 days, a week. My wife had her last shipment delayed MORE than a week. I don’t see how providing just two sensors per “month” (haha–that “month” is a lie) is going to provide enough supplies to have a sensor at hand, should something go wrong, and even if it doesn’t, 14-day wear, given the track record of 10-day wear sensors, is going to be truly IFFY.


#4

Will the new sensors use the same transmitters?


#5

@peter_alaimo

AFAIK:

The 14-day G6 sensors will not be a different sensor. It will be the same sensor as the 10-day G6 sensor.

It will be the transmitter which will be modified to allow the sensor to run for 14 days.

The sticky patch (adhesive) on the sensor is going to be changed but that is in the process of happening now on the current 10-day G6 sensor. Assuming Dexcom finds that change to be acceptable then they will submit to the FDA for a label change on the G6 system. I assume when the label change comes through, they would make a minor modification to the Transmitter such that all G6 Transmitters shipped after a certain date (or probably determined based on Transmitter Serial number greater than XXXX) would then run the sensors for 14 days.

Admittedly a great deal of speculation.

I could be wrong.

Time will tell.

On a slightly different note, any modification to the G6 transmitter would open the door for Dexcom to close the loopholes which currently exist by which the G6 sensors are able to be extended for additional sessions. The people working at Dexcom are really smart. It would be stupid to think otherwise. (lol). It becomes a question not of whether they are aware of this. Not whether then can close the loophole. But rather a question as to if they choose to close the loophole. As to that, I think it will be completely impossible to guess in advance and it will need to be tested once the revised transmitters are approved and start shipping.


#6

Thanks Tim. I appreciate it. Would the new transmitter also be required for the 1 hour warmup or could that be built into the sensors with the new adhesive or an update to the Dexcom G6 application?


#7

Not the sensor. But it could be an app change. Heck even the 14-day could be an app change. After all the xdrip can run longer than 10-days and can give data right from the start and bypass the 2-hour warmup - right?
So maybe all Dexcom would have to do is provide a remotely downloadable update for the Dexcom Receiver and a new SmartPhone app.
Although that would then mean that Tandem would also have to provide a new update to gain the benefits as well.

But yeah - Maybe the change in the receiver/app/pump makes more sense than a change in the transmitter.

All guesses.

:stuck_out_tongue:


#8

Yup, but with my G5’s I like to give the sensor about 20 minutes before having xDrip begin reading glucose values. And some sensors can be really, really flaky for the first few hours. I’ve also had about 3 or more over the course of 13 months that were all over the map for the first entire day. Another option is to let a G5 soak for a few hours (leaving in an “in-session” previous sensor) w/ an expired xmitter installed to keep things tidy as it warms up. Then xdrip should give good numbers from the gitgo for all but the “outlier” sensors (after swapping out the xmitters and removing the previous sensor). I’ve had issues with trying to let xdrip simply run continuously when swapping sensors, so now I just do a “fast” restart–giving just as few minutes for readings to begin).


#9

Stupid question, what does YSI stand for?
(I had issues googling it!)


#10

Yellow Springs Instrument. (it is a lab analyzer). In other words, they are comparing performance of the CGM to a lab analyzer.


#11

I installed a new G5 sensor (and xmitter) today and did a 15-minute start using xDrip. 90 minutes later it is still very accurate. I don’t use a meter much anymore but I checked out of curiosity–the sensor is tracking my bg’s as well as a meter.

EDIT: an hour later, and the xdrip app is showing “noise” on and off for about an hour.


#12

Everyone,
My son went from the G4 to the G6 a few months ago, and we’ve yet to get 10 days out of a sensor so far. While the G6 is relatively more accurate than the G4, the incidence of “compression lows” and “data drop outs” are now an every day discussion/shouting match at our house. Especially irritating when it happens in the middle of the night.

By the way, at 12:15 AM, he was at 176, a perfect dot if the graph were manually extrapolated to fill in the enormous pothole. So, total false low, gigantic variance when “compression” occurs, and multiple instances of “no data” even though his phone is at his bedside.

In short, I truly miss the G4’s data reliability.


#14

This is one of the things that has has held me back from adopting the G6. The other one is Medicare’s coverage for the G6 has not made its way completely through the bureaucratic process.

To be fair, I’ve experienced two sustained G4 data dropouts while sleeping recently. I’m thinking, however, that missing dots are preferable to inaccurate compression ones. I’m hoping that Dexcom is able to improve the G6’s reliability as time goes by. We might have to wait for its successor to do that.