FDA approves MiniMed 670G hybrid closed loop in unprecedented 3 months; Medtronic launching in spring 2017 in US; International approval expected in summer 2017 – September 29, 2016

In highly unexpected and truly outstanding news for patients and the field, the FDA has approved Medtronic’s MiniMed 670G hybrid closed loop and the new Guardian CGM sensor (previously called “Enlite 3”) following an unprecedented ~3 month review (submitted in June) – WOW! The 670G will launch in Spring 2017 in the US, and international approval is expected in Summer 2017. Read the FDA summary of safety/effectiveness data (75 pages), the FDA approval letter (six pages), Medtronic’s press release, FDA’s press release, and listen to an under-the-radar, brief stakeholder call with FDA’s Dr. Stayce Beck by dialing 1-866-454-1418.

This news represents a major milestone for diabetes technology; a testament to the hard work of thousands of committed people; a serious victory for JDRF, Helmsley Charitable Trust, and Medtronic; a spectacular showing of FDA CDRH’s patient centricity and insanely hard work ethic (Drs. Courtney Lias, Stayce Beck, and team worked many weekends to get this approved so quickly), and an event literally decades in the making.

We include key highlights from the earlier-than-expected approval below.

Launch Timing Highlights

1. Medtronic will launch the MiniMed 670G in the US in Spring 2017, ensuring payer coverage; market/manufacturing readiness; and appropriate training of employees, HCPs, educators, and patients. We’re glad to see the launch proceeding cautiously, since this has to be done right, particularly on the patient/HCP training and proper setting of expectations.

2. Regulatory approval of the MiniMed 670G is expected outside of the US in the summer of 2017 – this is the most specific timeline we’ve ever heard on the product’s international status.

FDA Approval Highlights

3. The 670G is FDA approved for people with type 1 diabetes 14+ years, though a pediatric study in 7-13 olds is enrolling to expand the indication (ending in December 2016).

4. The 670G is contraindicated in <7 year olds and those on <8 units of insulin per day.

5. According to the summary data, the FDA granted the MiniMed 670G Priority Review on July 13 “because the device is a novel technology and availability is in patients’ best interest.” Yes! In addition to the very strong pivotal data from ADA, the FDA summary includes reassuring safety data from the 99 trial participants that continued on the system after the pivotal wrapped up (pages 62-63). A few encouraging sentences on “patient perspectives” (page 74) are also included in the FDA summary. The FDA has not yet posted the 670G’s final labeling.

6. As part of this approval, the FDA is requiring a post-market study, which is presumably the ~1,000-patient study Medtronic’s Dr. Fran Kaufman first discussed at ATTD.

7. The terminology Medtronic uses is a fascinating part of this approval – the company is being careful to manage expectations, noting the 670G “automate(s) basal insulin delivery,” is a “hybrid closed loop” system, and the “latest innovation in Medtronic's phased approach toward developing a fully automated, closed loop system.” FDA’s Dr. Stayce Beck was also careful in this morning’s call to explain what the 670G can and cannot do.

8. The seven-day-wear Guardian CGM sensor (formerly called “Enlite 3”) has a labeled overall MARD of 10.6% on two calibrations per day (see page 45 here). As expected following FDA’s June AP Webinar, it does not have an insulin-dosing label claim. The summary data shows a slightly improved MARD of 9.6% with 3-4 calibrations per day, and the FDA actually says four calibrations per day “are recommended.”

9. In line with its guidance document, the FDA has approved the MiniMed 670G “system” as a combined set of devices: MiniMed 670G Pump, the Guardian Link Transmitter, the Guardian Sensor, One-Press Serter, and the Contour Next Link 2.4 Glucose Meter.

Pricing and Reimbursement Highlights

10. As we covered in the MiniMed 630G shipping news last week, Medtronic is offering a Priority Access Program to go from the newly launched 630G (threshold suspend on new pump platform) to the 670G hybrid closed loop ($0-$299). What is not clear is whether current in-warranty Medtronic pumpers on Revel or 530G pumps will be able to upgrade straight to the 670G, and if so, how it will be priced.

11. Medtronic told us the 670G will be commercially available at currently offered Medtronic pump system pricing. For context, the retail price of the MiniMed 630G system is $7,899.

Reflections on the Field, Competitive Landscape, and Key Questions

12. JDRF deserves enormous credit for knocking down the biggest gating factor to automated insulin delivery just a handful of years ago – FDA. This field would truly not exist without JDRF’s AP efforts, which only started in 2006. The FDA was also heroic in getting this approved so quickly; FDA’s Dr. Stayce Beck shared this morning that the team worked many weekends to make this happen, and dialogue with Medtronic has been ongoing for a few years now!

13. What is the impact on other pump companies? Will this approval push Animas, Beta Bionics, Bigfoot, Insulet, Tandem, and Roche faster? How quickly will they launch competitive products? Our Updated Automated Insulin Delivery (AID) Competitive Landscape puts Medtronic about a year ahead of the next hybrid closed loop approval (depending on when Animas launches; it’s pivotal is expected to begin in 4Q16).

14. How quickly will the 670G be adopted out of the gate by current Medtronic pumpers, non-Medtronic pumpers, and the majority of patients on MDI and fingersticks (for whom hybrid closed loop may be a big jump)?

15. How will payers view the 670G? Will Medtronic pursue other business models or special contracts? Or will the 670G initially be contracted like sensor-augmented pump therapy? Will payers make it hard to access automated insulin delivery if more patients than ever demand it? Will AID be cost-effective vs. best-in-class MDI + CGM + decision support?

Launch Timing Highlights

1. Medtronic will launch the 670G in the US in Spring 2017, ensuring payer coverage, market and manufacturing readiness, and appropriate training of employees, clinicians, educators and patients. We’re glad to see it is not rushing to launch the product, since this has to be done right: patients and HCPs need to be adequately trained. Nearly two years ago at JPM 2015, when CEO Omar Ishrak first laid down the timeline to launch this product by April 2017, it felt extremely ambitious (particularly given the regulatory challenges with the 530G). Medtronic will now hit the timeline easily, a testament to the rapid development, quick pivotal study, and remarkably fast review.

• Based on the wording in Medtronic’s press release, it sounds like launch might be carefully controlled at first: “Medtronic will begin commercial release of the MiniMed 670G system in the spring of 2017 with system availability increasing over time” and “As the company moves toward initial commercial release and subsequently to full production...” We wonder how high demand will be at launch and how Medtronic will prevent patient frustration for those dying to get on the system.

2. Regulatory approval of the MiniMed 670G is expected outside of the US in the summer of 2017 – this is the most specific timeline we’ve ever heard on the product’s OUS status, and well ahead of the JPM 2015 timeline to launch the 670G outside the US by April 2018. The 640G has seen excellent international adoption in recent quarters and sales should see a strong uptick with the 670G coming.

FDA Approval Highlights

3. The 670G is FDA approved for people with type 1 diabetes 14+ years, though a pediatric study in 7-13 olds is enrolling to expand the indication (ending in December 2016). We wonder if Medtronic will have the pediatric indication ready for launch by spring 2017. We also wonder if the system will be used widely off label in slightly younger children at launch, given the tremendous efficacy overnight (a huge win for parents of young children).

4. The 670G is contraindicated in <7 year olds and those on <8 units of insulin per day (boxed warning). The Summary Data notes, “Medtronic performed an evaluation of the 670G closed loop system and determined that it may not be safe for use in children under the age of 7 because of the way that the system is designed and the daily insulin requirements. Therefore this device should not be used in anyone under the age of 7 years old. This device should also not be used in patients who require less than a total daily insulin dose of 8 units per day because the device requires a minimum of 8 units per day to operate safely.”

• The 670G is also contraindicated in patients unable or unwilling to: (i) perform a minimum of four blood glucose tests per day (typical for pump therapy); (ii) maintain contact with their healthcare professional; (iii) carry the Medical Emergency Card provided with the system when traveling; and (iv) people whose vision or hearing does not allow recognition of pump signals and alarms.

5. According to the summary of safety and effectiveness data, the FDA granted the MiniMed 670G Priority Review on July 13 “because the device is a novel technology and availability is in patients’ best interest.” Yes! The FDA team under Dr. Courtney Lias has been highly committed to getting AID systems to market quickly, and Medtronic has clearly had a phenomenally productive dialogue with the Agency. Indeed, the Approval Letter shows that the PMA was actually amended seven times (!) following the June submission – that’s more than once every two weeks during the course of the three-month review. The FDA was truly heroic in getting this approved so quickly – Dr. Stayce Beck shared this morning that the team worked many weekends straight to make this happen in such a short time, and dialogue with Medtronic has been ongoing for a few years now.

• Medtronic presented very strong data at ADA from the single-arm, three-month 670G pivotal study that only began last June and wrapped up in March. We salute the FDA for allowing such a fast study focused on safety to support approval. Medtronic moved remarkably fast from pivotal complete to approval six months later – serious speed. The study results are included in detail on pages 33-39 in FDA’s summary data here. The pivotal data was also published as a brief JAMA Research Letter during EASD two weeks ago.
• The FDA summary data also includes encouraging new safety data from the 99 pivotal trial participants that chose to continue on the system (pages 62-63). Patients were in the continued access study from October 23, 2015 to April 26, 2016. There were only sixteen adverse events reported during the continued access phase, which we assume was more than 5,000 patient days of use. Only three of those adverse events were device related: two episodes of severe hyperglycemia and one infection. It was good to see no device-related severe hypoglycemia, a testament to the 670G safety and ability to reduce hypoglycemia. The summary data does not share further details about the severe hyperglycemia episodes, but both patients recovered without sequela. We assume this data only bolstered the FDA’s confidence in the device’s safety.
• The summary data also includes “patient perspectives” (page 74)! We’re very glad to see the FDA device division including this, even if it’s only a few sentences: “Patient perspectives considered during the review included: Patients want a variety of devices that provide information and aid in management of their glucose control to inform decision making with their health care providers on lifestyle changes and treatment decisions. Patients have also expressed that they want devices that provide features that enable automated insulin delivery, and are willing to accept reasonable risks related to such devices. This information was gathered during patient oriented conferences and face-to-face meetings with patients.”
  
  • Dr. Stayce Beck emphasized this morning that patient perspective played a very important role in approving this device: “I think that hearing from patients has given us a better understanding of what daily life is like living with diabetes. It’s helped us to understand how much impact devices like this have.”
• The FDA has not yet posted the 670G’s final labeling, though the Approval Letter says the final labeling should be submitted “as soon as possible and before commercial distribution.” This will take the form of an amendment to the PMA submission, and we look forward to seeing how it compares to the Summary Data and Approval Letter language.

6. As part of this approval, the FDA is requiring a post-market study, which is presumably the ~1,000-patient study Medtronic’s Dr. Fran Kaufman first discussed at ATTD. Within 30 days, Medtronic must submit a PMA supplement that includes complete protocol of its post-approval study to provide additional confirmatory safety outcomes data collected in a controlled clinical study for one year.

• Per ATTD, the multinational trial will enroll a representative type 1 population (spectrum of A1cs and ages), randomizing patients to three groups: pump alone, sensor-augmented pump (no automation), or the MiniMed 670G (IF only there was a fourth group on MDI!). The primary endpoint will be glycemic control AND hypoglycemia. The study will generate excellent real-world outcomes data, and we especially hope it is powered to show changes in severe hypoglycemia and tracks healthcare costs.
• Many have wondered if other companies will also need to do such a large post-market trial – we’ll have to wait and see, as Tandem, Animas, Insulet, and others have not talked about this publicly. We assume the FDA will be highly flexible and believe (based on this morning’s call and other comments) that companies will be able to choose how much data collection they want to do pre-market vs. post-market. Medtronic chose the fastest pre-market path and has opted to stack most of the data post-market. It will be interesting to see what other companies do, as they are now playing catch-up and the pressure is on to get products to market quickly.

7. The terminology is a fascinating part of this approval – Medtronic is being careful to manage expectations, noting the 670G “automate(s) basal insulin delivery,” is a “hybrid closed loop” system, and the “latest innovation in Medtronic's phased approach toward developing a fully automated, closed loop system.” FDA’s Dr. Stayce Beck was also careful in this morning’s call to explain what the 670G can and cannot do, and where it falls on the spectrum of improvements: “It is important to understand that this device is not automatic. There is still a need for user interaction...This is a breakthrough for people with diabetes, but it is in no way a cure – it does not take everything away. But it is a step in the right direction.”

• We’re psyched to see caution with the terms and managing very dangerous “I don’t-have-to-do-anything” expectations. Speakers like Dr. Trang Ly (at ADA) and Dr. Aaron Kowalski (ADA, AADE) expressed worry on this front with a first-gen hybrid closed loop product – particularly among the early adopter patients that are more likely to get on the 670G and more likely to be frustrated if the system is conservative.
• The Medtronic press release is worth a read, which mostly uses the term “Hybrid Closed Loop System.” Though at one point it does say “the system requires minimal input - patients only need to enter mealtime carbohydrates, accept bolus correction recommendations, and periodically calibrate the sensor.” Enthusiastic pivotal study lead author Dr. Rich Bergenstal is quoted, as is JDRF CEO Derek Rapp and Medtronic Chief Medical Officer Dr. Fran Kaufman. We think the release is worded well and speaks to how much was learned from the initial launch of the MiniMed 530G (which was inaccurately positioned as a fully closed-loop artificial pancreas, receiving lots of flack from patients).
• Interestingly, the FDA press release uses the term “Automated Insulin Delivery device,” a departure from “Artificial Pancreas” used in the guidance. Dr. Courtney Lias spoke on this point at AADE, and we’re glad to see FDA adapting its vocabulary as the field seems to be moving away from using “artificial pancreas” (though JDRF does still use it). The FDA press release notably quotes Dr. Jeffrey Shuren (CDRH Director) and Dr. Alberto Gutierrez (Director of the Office of In Vitro Diagnostics and Radiological Health). We have said it for the past couple of years, but it is worth repeating – the FDA device division (under the diabetes leadership of Drs. Courtney Lias and Stayce Beck) deserves enormous credit for moving this field along.
  
  • There is still poor consensus on what to call these devices. Some argue that the abbreviation for “Automated Insulin Delivery Systems” – AIDS – is also sub-optimal. We wonder if “hybrid closed loop” will take hold. Insulet is calling its product the “Horizon Automated Glucose Control System,” yet another term.
• As a reminder, the 670G hybrid closed loop algorithm (ePID) automatically increases or decreases basal insulin, but all boluses require user input and confirmation (i.e., meal and correction boluses). This means that a missed meal bolus on the 670G hybrid closed loop could still mean several hours above range, as the higher basal rate will take a while to bring blood glucose back in zone. Still, the system is clearly much better than most patients are doing right now, and the hybrid closed loop is a great way to go with a first-gen product; until insulin gets faster; and until algorithms get even smarter. Plus, basal modulation is incredibly effective overnight (see the 670G pivotal data), where even type A patients cannot beat an automated algorithm that works while they are sleeping.
  
  • The 670G algorithm, when in “Auto Mode” (hybrid closed loop) targets 120 mg/dl, which can be raised to 150 mg/dl during exercise. It has a max limit on insulin delivery per hour. The algorithm gives a new dose every five minutes and uses open-loop parameters to initialize hybrid closed loop (total daily insulin, basal, insulin:carb, insulin sensitivity factor). At the start of hybrid closed loop (Auto Mode), there is a sensor accuracy check, along with a glycemic target adjustment for a smooth transition to closed-loop. The pump needs 48 hours of open loop therapy (Manual Mode) before closed-loop can be entered for the first time. The algorithm can adapt over time as things change (e.g., sickness requiring more insulin), and the 670G will revert to open loop if the sensor is inaccurate. The system will also switch to safe mode or the pre-programmed basal rate in cases like sensor failure.
  • In Manual Mode, the 670G has three options: sensor-augmented pump therapy (traditional open loop), low glucose suspend (“suspend on low”; i.e., 530G/Veo), and predictive low glucose management (“Suspend before low”; i.e., 640G). We’re glad to see a range of options, though do wonder how hard it will be to train patients and HCPs on the differences.

8. The seven-day-wear Guardian CGM sensor (formerly called “Enlite 3”) has a labeled overall MARD of 10.6% on two calibrations per day (see page 45 here). As expected following FDA’s June AP Webinar, it does not have an insulin-dosing label claim. The summary data shows a slightly improved MARD of 9.6% with 3-4 calibrations per day, and the FDA actually says four calibrations per day “are recommended.”

• This is much-improved accuracy relative to Medtronic’s original Enlite sensor, putting it closer to Dexcom’s G5 (MARD of 9% on two calibrations per day) and right in the ballpark of Abbott’s factory calibrated FreeStyle Libre (MARD of ~11%, but no calibration needed).
• The FDA approval letter is very clear on the adjunctive labeling – patients are NOT advised to make treatment decisions (e.g., bolus) based on Guardian CGM values: “The Guardian Sensor is intended for use with the MiniMed 670G system to continuously monitor glucose levels in persons with diabetes. It is intended to be used for detecting trends and tracking patterns in persons aged fourteen years and older, and to be used by the MiniMed 670G system to automatically adjust basal insulin levels. It is indicated for use as an adjunctive device to complement, not replace, information obtained from standard blood glucose monitoring devices.”
  
  • We wonder if this will be an advantage for Dexcom CGM-driven systems, as G5/G6 will presumably have an insulin-dosing label claim by the time those systems launch. Per Dexcom’s 2Q16 call, FDA discussions are ongoing on this topic (~2 years now). We’re not positive if all of the Dexcom-driven systems will include automatic correction boluses (see our competitive landscape)– as far as we know, Bigfoot Biomedical, Beta Bionics, potentially Insulet, and potentially Tandem’s TypeZero product will have such functionality, meaning they could offer tighter control than the 670G. This is speculative, however.
• We wonder how much baggage Medtronic will have to overcome from the original Enlite. Will there be resistance to trying Guardian among those underwhelmed with the previous sensor? We know of many patients that have tried Medtronic CGM and given up because of the poor accuracy. That said, most pivotal trial participants we’ve talked to say the Guardian sensor (Enlite 3) is comparable to Dexcom’s accuracy. It will be interesting to see how patients compare the systems.

9. In line with its guidance document, the FDA has approved the MiniMed 670G system as a combined set of devices: MiniMed 670G Pump, the Guardian Link Transmitter, the Guardian Sensor, One-Press Serter, and the Contour NEXT Link 2.4 Glucose Meter.

• We assume other automated insulin delivery devices in development will need to follow a similar “system” route in the near-future, meaning companies like Tandem and Bigfoot and Beta Bionics will presumably need to partner with a glucose meter company (Animas obviously has LifeScan in house; Insulet has its Abbott BGM partnership). We’re not positive about this, however, as the Animas Vibe and t:slim G4 were not approved with a glucose meter.
  
  • Longer-term, Dr. Courtney Lias has talked about the potential for “component” AID systems, but this will take significant strides in interoperability and changes in how FDA regulates; see more from her positive talk at NIH’s July AP Workshop and her ADA D-Data talk.

Pricing, Upgrades, and Reimbursement Highlights

10. As we covered in the MiniMed 630G shipping news last week, Medtronic is offering a Priority Access Program to go from the newly launched 630G (threshold suspend on new pump platform) to the 670G hybrid closed loop ($0-$299). What is not clear is whether current in-warranty Medtronic pumpers on Revel or 530G pumps will be able to upgrade straight to the 670G, and if so, how it will be priced. We might assume the out-of-pocket will be similar to the upgrade price to go from a Revel/530G pump to the 630G, which is $599 or $3,100 out of pocket (depending on whether the old pump was purchased after or before May 1, 2016, including a $400 trade in credit).

• While the 670G will be a compelling upgrade from sensor-augmented pump therapy, we wonder how many current in-warranty Medtronic patients will pay the cash price to upgrade (we assume it will be $3,100 for the majority of Medtronic users on pumps purchased before May 1, 2016).
• The pump market is a not a particularly fluid consumer market – given the four-year warranty lock in –how fast will Medtronic’s installed base convert over to the 670G? Will the 670G see a typical adoption curve?

11. Medtronic told us the 670G will be commercially available at currently offered Medtronic pump system pricing. For context, the retail price of the newly launched MiniMed 630G is $7,899 for the pump, transmitter, meter. Other business models and payer relationships are certainly possible (e.g., one monthly subscription price, service models, etc.), though it will not be easy for a company like Medtronic to quickly change its business model. We wonder how it might evolve in the next year, three years, and five years.

Reflections on the Field, Competitive Landscape, and Key Questions

12. JDRF deserves enormous credit for knocking down the biggest gating factor to automated insulin delivery just a handful of years ago – FDA. This field would not exist without JDRF’s efforts. Adam often reflects back on the 2010 FDA/NIH AP Workshop Meeting (his first year at Close Concerns), where approval of the MiniMed 530G/Veo looked like a true long-shot. It’s been six years since that tense meeting, but boy has the field come a long way to the first commercial hybrid closed loop device.  

• The final 2012 artificial pancreas guidance (which JDRF heavily influenced after the off-the-mark draft guidance) really paved the way for Medtronic to blaze a trail on getting this product to market quickly, including a single-arm, three-month pivotal trial. We salute former JDRF CEO Jeffrey Brewer and Chief Mission Officer Dr. Aaron Kowalski for starting this program at JDRF, and for the Helmsley Charitable Trust for funding that initial grant to build the team. Read JDRF’s enthusiastic press release here (“JDRF Celebrates FDA Approval of Artificial Pancreas System”), which really summarizes the non-profit’s achievements over the past decade.
• The FDA was truly heroic in getting this approved so quickly; FDA’s Dr. Stayce Beck shared this morning that the team worked many weekends to make this happen, and dialogue with Medtronic has been ongoing for a few years now. The Agency has worked creatively to clear the path to market, and we would have never thought a device of this magnitude could have a three-month, single-arm pivotal study and a subsequent three-month review – wow! On the other hand, the 670G is so much safer than what so many patients are doing right now, and it is abundantly clear the Agency recognizes this.
• Drs. Richard Bergenstal and Aaron Kowalski summed the news up well in emails to us:
  
  • “Being mindful of expectations, this is still one of those landmark days – where so much hard work by so many – results in an advancement in diabetes management we have strived for over the last 30 years as we watched pumps improve and sensors improve and now the two working in concert to help improve the lives of people with T1D. Amazing!” – Dr. Bergenstal
  • “It's a great day for people with diabetes.” – Dr. Kowalski

13. What is the impact on other pump companies near term? Will this approval push Animas, Beta Bionics, Bigfoot, Insulet, Tandem, and Roche faster? How quickly will they launch competitive products? Our Updated Automated Insulin Delivery Competitive Landscape puts Medtronic about a year ahead of the next hybrid closed loop approval (depending on when Animas launches; it’s pivotal is expected to begin in 4Q16). Tandem plans to launch a predictive low glucose suspend (PLGS) system in 2017, though its pivotal won’t begin until 1Q17 (and its hypoglycemia-hyperglycemia minimizer isn’t expected until end of 2018).

• Dr. Stayce Beck made it clear that the Agency wants to see many AID devices on the market: “We know that not every device is for every person. We want to be getting lots of products out there. There are people who want to go on this device, and there will be others who want to give up that control. Part of our goal is getting choices out there for people... This is something the FDA was committed to; we are not just waiting and seeing. I’m hopeful other companies are not too far behind. Each system will work different for different people.”
• Dr. Beck also encouraged companies to talk to the FDA early and often. Conversations with Medtronic have been going on for a few years, enabling the Agency and the company to agree on an efficient clinical trial pathway to market.
• How quickly will Medtronic iterate on the 670G and improve it with new generations? The company’s MiniMed 690G (incorporating the DreaMed MD-Logic algorithm to add automatic correction boluses) completed a feasibility study in June 2016, and a bridging study has NIH funding. We’re not sure of the commercial timing on this product, but it is clearly moving through development.

14. How quickly will the 670G be adopted out of the gate by current Medtronic pumpers, non-Medtronic pumpers, and the majority of patients on MDI and fingersticks (for whom hybrid closed loop may be a big jump)? This is probably the biggest question for the entire field, since there many companies currently fighting over a fairly small type 1 market currently on pumps. Will automated insulin delivery dramatically expand the market, or will it mostly appeal to current pumpers? Will AID penetrate into type 2? How many product generations will it take to expand beyond early adopters? Can the cost go down dramatically to ensure broad accessibility?

• Will Medtronic be able to manage patient expectations? HCP expectations? How much will the initial launch be controlled?
• What will the average diabetes clinician think of the MiniMed 670G? Will PCPs be able to prescribe it? How much training and support will clinicians need for the 670G? How quickly will the 670G’s usability and prescribing and startup improve with subsequent product generations?

15. How will payers view the 670G? Will Medtronic pursue other business models or special contracts (e.g., its UHC agreement)? Or will the 670G initially be contracted with payers like sensor-augmented pump therapy? Will payers make it hard to access automated insulin delivery if more patients than ever demand it? Will hybrid closed loop be cost-effective relative to best-in-class MDI + CGM + decision support? As MDI + CGM becomes more compelling with Bluetooth-enabled pens and smart open-loop algorithms, will automated insulin delivery face tougher competition? How much of a threat are SGLT-2 inhibitors for type 1 diabetes?

-- by Adam Brown and Kelly Close