CGM and Closing The Loop

CGM and Closing The Loop

Dualities Research: Helmsely Charitable Trust, ADA, JDRF, NIDDK Consulting: Abbott Diabetes Care, Roche, Intarcia, Valeritas, Adocia, Big Foot

Like With Pumps, We ve Come A Long Way With CGM

Sensors: Continual Evolution For the Near Future Guardian Sensor 3 Freestyle Libre Glysense Implantable Sensor Raise you hand if you use the FreeStyle Libre Pro routinely in your practice? Dexcom Gen 6 Sensionics Implantable Sensor

What s Going On? 85 y/o man, no cognitive concerns, changed 5 years ago to multiple injections from 70/30 premix Mean/SD on glucose testing at home 185/60 testing 2.5 times daily on meter first started to use 18 months ago HbA1c now 11.8% What to do?

No glycation gap! Not enough blood on new CMS meter, readings consistently low when compared to FGM

Fingerstick BG 95 162 188

CASE 2 69 y/o woman with 35 years T1D Stage 3 CKD, + CAD s/p stent, +PDR, recent toe amputation No hx severe hypoglycemia HbA1c stable X years around 8% Refuses to test more than 2-3 times/day (and sometimes less than that!) What to do?

CASE 2 Freestyle Libre Pro: Where to start?

CASE 2

CASE 2 What she needs: Less basal Give prandial insulin (and check BG) before eating!!

Medtronic Guardian Connect: Possibly Available Later this Year

Dexcom G6: 2018

Dexcom/Verily CGM: Gen 1 Available Late 2018; Smaller Gen 2 Available 2020-2021

Sensionics Eversense: Under FDA Review: Possible Approval Late 2017

Sensionics.com Florescence to transmitter

Sensor Longevity Median sensor life: 149 days Diabetes Care 2017;40:1-6

What is AP? CGM + Pump + Controller Controller: laptop, tablet, phone to start, chips will get smaller

Our Current Pathway to AP (Closed Loop)

Past, Present, and Future of CSII/AP CSII LGS and PGS Lancet Diabetes Endocrinology 2014; 2:701-709 SAP Nocturnal CL HCL DT&T, 2017

ARTIFICIAL PANCREAS

Raise Your Hand if You Have Patients on Our First Hybrid Closed Loop? Patient still needs to bolus for meals and notify the system for exercise. Won t be for everyone-many love it, others don t want the extra burden on their diabetes, yet others don t find it aggressive enough.

Key Pearls for 670G for Hybrid Closed Loop Patients HAVE to use bolus calculator for auto mode to engage In auto mode, glycemia is maintained by changing basal doses Manual mode basal rates have no bearing in auto mode Meal doses: generally need higher doses (ICR), IOB 2-3 hours work best; algorithm determines auto basal, ISF, targets! Programmed manual mode ISF dose not apply in auto mode Calibration of CGM: 3-4 times daily

Medtronic 670G Pivotal Trial Bergenstal, et al: JAMA 2016;316:1407, Garg et al: DT&T 2017;19:155-163 Single-arm, non-randomized, 3 months N = 124 (n=94 adults, 30 adolescents) Baseline A1C 7.4%; mean reduction 0.5% Those with baseline > 7.5% reduction by 1.0% Time < 70 mg/dl reduced by 44%, < 50 mg/dl by 40% Time in range increased 72% 1.4 kg weight increase in adults, 1.0 kg weight gain in adolescents MARD 10.3%

All patients

Adolescents

More Information About the 670G No control group: an up-coming 1000 patient trial is underway Two on-going pediatric studies in 7-14 year-olds and 2-6 year-olds DreaMed MD Logic (Fuzzy Logic): incorporate automatic correction doses: bridge funding from NIH secured. This product will be called Medtronic 690G

More To Think About with our First HCL Psycho-social studies now on-going: little now known how will this impact QOL for needing to unlearn behaviors (eg., hypo Rx with down arrow) Are expectations too high, especially for clinicians in non-centers of excellence? What about type 1 patients not seen by endocrinologists. How will the elderly do with this technology?

Components of a Bi-Hormonal AP (Bionic Pancreas) Are 2 hormones better than 1? Are we better off with glucagon, pramlintide, or GLP-1?

Finally: Some Data For What We ve All Been Wondering! N = 10; CL, then 4 weeks 60 mcg PRAM ac Mean age 20 years, 9 years T1D, A1C 7.2% N = 11: CL, then 4 weeks 1.8 mg daily LIRA Mean age 22 years, 10.5 years T1D, A1C 7.5% Meals were not announced Diabetes Care 2016;39:1127 1134

CL vs. CL + PRAM or LIRA Adjunctive Rx: Purple Control: Green Diabetes Care 2016;39:1127 1134

CL vs. CL + PRAM or LIRA CL vs. CL + PRAM CL vs. CL + LIRA 3.5 3.5 3 2.5 2 1.5 1 0.5 0 P<0.001 2.9 1.6 Time to Peak G (h) 3 2.5 2 1.5 1 0.5 0 P=NS 1.8 1.8 Time to peak G (h) CL alone CL + PRAM CL alone CL + LIRA CL vs. CL + PRAM CL vs. CL + LIRA 150 100 50 0 P<0.001 96 59 [VALUE] [VALUE] 0 Glucose Spike Glucose spike CL CL + LIRA CL CL+PRAM 150 100 50 Diabetes Care 2016;39:1127 1134 P=0.05

CL vs. CL + PRAM or LIRA TIR during daytime better with PRAM (p<0.004) but not LIRA (p=ns). Neither drug with better TIR overnight LIRA: better weight loss (3.2 kg) compared to PRAM (0.7 kg) Longer-term studies with these adjunctive agents are warranted. Diabetes Care 2016;39:1127 1134

Don t Give Up On Pramlintide Just Yet! Basal-bolus pram-regular insulin (9 mcg/unit fixed ratio) proof of concept Two period cross-over trial, N = 32 adults with T1D, HbA1c 8.1% ADA Abstract 1121P, 2017

But What About Glucagon? Would this be a better adjunctive hormone to infuse in a CL system?

Bihormonal AP 2014

ẞeta ẞionics 2017

Mean CGM and Percentage <70 mg/dl Bionic Pancreas vs Usual Care (Adults) 159+30.4 <70 = 7.3% 2017: stable liquid glucagon analogue: ZP4207 from Zealand Pharmaceuticals 133+13.4 <70 = 4.1% <60 = 3.7% <60 = 1.5% Russell et al. New Engl J Med 2014; 371:313-325

Bionic Pancreas Plan Start with insulin-only studies 2017-2018 Dual-hormone

Insulet: OmniPod Horizon HCL As of July, 2017: pod talks directly to Dexcom G6 82 patients tested for over 3300 hours

Big Foot Smart Loop: Hopeful Launch 2019

TypeZero Technologies Commercial side of UVA s AP projects Private company currently backed by angel investors and early stage venture capital Products will range from closed loop systems to cloudbased predictive analytics, to smart bolus calculators to clinician tools for therapy optimization

TypeZero Development Partners CellNovo Sensionnics Tandem

My Questions Could a more automated pump system make the therapy simpler and more efficient so both clinical endocrinologists and non-specialists can easily oversee closed loop systems with better A1C levels with less hypoglycemia? OR, will this create a greater clinical burden making this therapy an even greater hassle requiring more infrastructure than it does now? Raise your hand if you think the administrative burden managing all of this new technology from your offices and clinics will be MORE than it is now! Will payers want to pay for this if the cost is more than a pump and sensor alone? (BTW-many Medicaid patients in WA state are now back on human insulin)

Conclusions CGM technology is exploding and integration with pump therapy is finally about to become a reality outside of academia and research centers Still It is unclear to me how access for patients, training for physicians, and cost will make this standard of care for tens of thousands of patients