The artificial pancreas: the next step in connectivity and digital treatment of type 1 diabetes

Transcription

1 The artificial pancreas: the next step in connectivity and digital treatment of type 1 diabetes Roman Hovorka PhD FMedSci University of Cambridge, UK

2 Duality of interest declaration Advisory Panel: Research Support: Speaker s Bureau: License fees: Other: Merck, Novo Nordisk, Artsana Minimed Medtronic, Abbott Diabetes Care Novo Nordisk, Eli Lilly BBraun, Medtronic Patents and patent applications

3 Content (Not so) hot news Closed loop outpatient studies: Randomised clinical trials Outlook

4 US Launch spring 2017 Outside US launch spring 2018 (or later)

5 GCSE 2016 AQA Further Additional Science 17,174 students 16 year old

6 The artificial pancreas sensor insulin pump control algorithm

7 Diabetes technology Glucose responsive insulin delivery Glucose monitoring Closed loop systems SMBG devices Continuous glucose monitoring Insulin delivery Pens, smart pumps, bolus wizard, patch pumps Infusion sets and catheters Insulins Ultrarapid, rapid, long acting (inhaled)

8 Hybrid closed-loop

9 Outpatient Randomised Clinical Trials

10 Adolescents overnight camp study 1 night RCT Closed loop vs SAP Adolescents (n=56) Three-centre Baseline A1C 8.0% 23:00 to 07:00 data Fewer episodes below 3.5mmol/l Reduced number of hypos Phillip et al NEJM 2013; 368:

11 Cambridge closed-loop prototypes

12 Cambridge free-living studies since 2012 N = centres, adults pregnancy, adolescents, children 4 RCTs night only over 3 to 12 weeks 6 RCT 24/7 over 1 to 12 weeks total closed loop operation 125,949 hours 4,248 days 14.4 years

13 Adult 24/7 home study 12 week RCT Closed loop vs SAP Adults (n=33) Three-centre Baseline A1C 7.6% 24 hour data Time in target 11% Mean glucose 0.6mmol/l Hypo AUC 2/5 HbA1c 0.3% Improved time in target and time below target Thabit, Tauschmann et al NEJM ;373(22):

14 Teens 24/7 home study 3 week RCT Closed loop vs SAP Teens (n=12) Single-centre Baseline A1C 8.5% 24hour data Time in target 19% Mean glucose 1.8mmol/l Improved time in target Tauschmann et al Diabetes Care Nov;39(11):

15 Free living home use: No remote monitoring or supervision

16 Pregnant women overnight home study 4 week RCT Closed loop vs SAP Adult (n=16) Single-centre Baseline A1C 6.8% Overnight data Time in target 15% Mean glucose 0.8mmol/l Improved time in target no change in hypo burden Stewart et al NEJM ;375:644-54

17 Overnight closed-loop at home in pregnant women Courtesy of Dr Helen Murphy and Dr Zoe Stewart

18 Pregnancy interview data: benefits of AP usage Interview data confirms previously-known benefits (e.g. Barnard et al, 2014) Reassurance, improved sleep, reduced worry, time off from diabetes, feelings of normality Interesting additional themes Empowerment It s made me be a bit more on top of things. It s changed my life. You feel really, well, you re in control. Excitement It s quite exciting to know that I can learn something like this and make it work. I think it s like a crystal ball seeing what it s going to be like for all diabetics in 60 years 30 if you think positive. Courtesy Conor Farrington

19 670G Hybrid closed-loop PID controller N=124 3 months years HbA1c 7.4%(0.9) Bergenstal et al JAMA 2016

20 Adult 24/7 hotel vs home study 5 nights RCT Closed loop (hotel) vs SAP (home) Adults (n=10) Two-centre Baseline A1C 7.0% 23:00 to 07:00 data Time in target 22% Mean glucose 1.7mmol/l Improved time in target and no change in hypo burden Brown et al Diabetes Technol Ther Mar;17(3):203-9

21 5-9 year old 24/7 camp study 3 days RCT Closed loop vs SAP Preadolescents (n=30) One-centre Baseline A1C 7.3% Overnight data Mean glucose 1.3mmol/l Hypo 3.9mmol/l 2.2% Increased mean glucose reduced time below target Del Favero et al Diabetes Care 2016 Jul; 39(7):

22 Bi-hormonal closed-loop system at camp 5 days diabetes camp RCT (usual therapy) Young children 6-11 years (n=19) Baseline A1C 7.8% 24 hour data Time in target 23% Mean glucose 1.7 mmol/l Hypo 3.3mmol/l 1.6% Overnight data Time in target 32% Mean glucose 2.6 mmol/l Hypo 3.3mmol/l 2.2% Russell et al, Lancet Diabetes Endocrinol. 2016;4(3):233-43

23 Single vs dual hormone overnight closed loop at camp Adolescents and adults N=28 2 nights per treatment Haidar et al, JCEM 2016

24 Dual hormone closed-loop Benefits Increased hypoglycaemia protection More aggressive insulin delivery Challenges Room-temperature stable glucagon Dual-chamber pumps (and two catheters) Insulin trumps glucagon Meal bolus required Chronic sc delivery biological risks Cost Russell et al, Diabetes Care, 2012 Castle et al, Diabetes Care, 33, 2010 El Khatib et al, Sci Transl Med, 2, 2010

25 Variability in insulin requirements (adults) Ruan Y et al, Diabetes Care. 2016;39:830-2

26 Commercialisation of artificial pancreas single single dual single single dual single single Kropff et al, Diabetes Technol Ther. 2016;18 Suppl 2:S253-63

27 OpenAPS

28 Outlook: Cambridge and colleagues APCam11: 6 years to adulthood over three months Dan05: 6 to 18 years adulthood over 12 months CLOuD: newly diagnosed years over 24 months Children aged 1 to 7 years 60+ years over 4 months

29 CLOuD study: newly diagnosed youth Closed loop within 6 weeks of diagnosis 2 year closed loop use Primary endpoint residual C-peptide secretion Clinicaltrials.gov NCT

30 Closed-loop on general ward Tablet with control algorithm Nav 2 glucose sensor CGM receiver Insulin pump Nav 2 sensor: No interference with paracetamol containing drugs Fully closed system (no meal announcement) Thabit et al Lancet Diabetes Endocrinol Feb;5(2):117-12

31 Glucose levels and insulin delivery Sensor glucose Insulin delivery Thabit et al ADA 2017

32 Clinical practice adoption Adoption challenges Approved system Target populations Training Reimbursement Performance barriers Speed of insulin absorption/reliability of insulin delivery Sensor reliability

33 Thank you