l Research and Grant Support to Employer: Future...
Transcript of l Research and Grant Support to Employer: Future...
![Page 1: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/1.jpg)
David G Robertson MD
Atlanta Diabetes Associates
Atlanta, Georgia
Future Directions in Diabetes
Management
Disclosures
l Research and Grant Support to Employer: Janssen, Lilly, Pfizer, Novo Nordisk, Eisai, Agramatrix
l Consultant: Lilly
l Speaker’s Bureau: AstraZeneca, Lilly, Abbvie, Novo Nordisk, Boehringer Ingelheim
Topics
l Insulin the future
l Type 2 Diabetes: More drugs or new approaches
l Type 1 : Until Islet transplants, what options are close?
Insulin the future
l Ultra Fast Acting Prandial Insulins
– Inhaled
– Subcutaneous
– Oral
l Ultra Long Acting Basal Insulins
![Page 2: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/2.jpg)
Insulin of the future: Oral?
l Oramed annouced 11/3/14 results of 7 days of treatment in Type 1 patients
– Small decrease in daytime glucose values
– Moderate decrease in nightime glucose values
– No increase of ypoglycemia
– Small decrease in insulin needs
l May also be able to deliver exenatide orally
Type 2 Diabetes: More drugs or new approaches
l Multidrug therapy at diagnosis
l Kidney Specific SGLT1 cotransport inhibition
l Prevention investment
l Bariatric Surgery:
– Could we actually save money?
![Page 3: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/3.jpg)
![Page 4: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/4.jpg)
Topics
l Insulin the future
l Type 2 Diabetes: More drugs or new approaches
l Type 1 : Until Islet transplants, what options are close?
The image shows human-embryonic-stem-cell-derived
beta cells that have formed islet-like clusters in a mouse
http://harvardmagazine.com/2014/10/melton-creates-beta-cells
Islet-like cluster of beta celss derived from stem cells
![Page 5: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/5.jpg)
STAP stem cells: acid washing of adult cells converted to plueropotent stem cells A FRAUD
Nature 511, 5–6 (03 July 2014)
doi:10.1038/511005b
Viacyte system for insertion of embryonic beta cells into a patient fot 1 to 5 years
http://viacyte.com/products/encaptra-drug-delivery-system/
Cartoon of Cell Encapsulation
1919
• Cells implanted in environment where they are secluded from host
immune system
• Cells sense and respond to ambient metabolic conditions
"CAUTION--Investigational device. Limited by Federal (or US) law to investigational use."
Interstitial Glucose Readings
![Page 6: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/6.jpg)
Artificial Pancreas: Fundamentals of
closed-loop systems
HCL FCLTS PLGM
Subject Burden Automation
Regulatory Ease System Complexity
Example of Threshold Suspend Cycle
22
Suspend time maximum = 2 hrs
Insulin infusion stops
Basal insulin infusion will resume even if glucose is below
Thresh Suspend limit
Basal Insulin Basal Insulin2 Hour Suspend
Insulin Suspends for 2 hours / Resumes for 4 hours
Automatically suspends insulin delivery if sensor glucose reaches the user-set limit
ASPIRE In-Home Study: Results
Study conducted with Veo pump that is not FDA approved and not commercially available in the US. Study data and final report have not been submitted to FDA.
Bergenstal RM, Klonoff DC, Garg SK, et al. Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med. 2013;369(3):224-232.
The severity and/or duration of nocturnal hypoglycemic events was lower in the Threshold Suspend Group.
1547 980 1406 1568
37.5% reduction (p<0.001)
ASPIRE In-Home Study: Results
Hypoglycemic events were less frequent in the Threshold Suspend Group.
Study conducted with Veo pump that is not FDA approved and not commercially available in the US. Study data and final report have not been submitted to FDA.
Bergenstal RM, Klonoff DC, Garg SK, et al. Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med. 2013;369(3):224-232.
30% reduction (p<0.001)
32% reduction
(p<0.001)
![Page 7: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/7.jpg)
ASPIRE In-Home Study: Results
∆A1C was similar in the two groups. The 95% CI of the difference in ∆A1C (-0.05, 0.15) did not include the non-inferiority limit of 0.4%.
Study conducted with Veo pump that is not FDA approved and not commercially available in the US. Study data and final report have not been submitted to FDA.
Bergenstal RM, Klonoff DC, Garg SK, et al. Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med. 2013;369(3):224-232.
Predictive Low Glucose Suspend
Danne, Diab Technol Ther 2014
Predictive Low Glucose Suspend
Danne, Diab Technol Ther 2014
• N=16
• Hypoglycemia
averted in 13
Predictive Low Glucose Suspend –
Larger Scale Testing
0%
10%
20%
30%
40%
50%
< 70 < 60 < 50
Control Intervention
Maahs, Diab Care 2014
0%
10%
20%
30%
>30 min
>60 min
>120 min
>180 min
Control Intervention
Nights with Hypoglycemia Duration of Hypoglycemia
• N=45, 900+ nights
![Page 8: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/8.jpg)
In-Home Overnight CL – Fuzzy Logic
Nimri, Pediatr Diab 2014
• N=15, 4 nights
Overnight CL – Outpatient Study
Hovorka, Diab Care 2014• N=16, 3 weeks
Overnight CL – Outpatient Study
Hovorka, Diab Care 2014
![Page 9: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/9.jpg)
Medtronic Ambulatory Closed-Loop System Overnight CL – Feasibility
O’Grady, Diab Care 2012
• N=8, 1 night
Overnight CL – Multiple Nights
Ly, Diab Care 2014
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:000
40
80
120
160
200
240
280
320
360
400
Glu
cose
(m
g/d
L)
Date: 1-Oct-2014
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:000123456789
101112131415
Infu
sio
n R
ate
(U
/h)
Clock (HH:MM)
![Page 10: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/10.jpg)
00:000
40
80
120
160
200
240
280
320
360
400G
luco
se (
mg
/dL
)
00:000
1
2
3
4
5
6
7
8
9
10
Infu
sio
n R
ate
(U
/h)
18:00 20:00 22:00 00:00
18:00 20:00 22:00 00:00
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00
Date: 1-Oct-2014
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00
Clock (HH:MM)
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:000
40
80
120
160
200
240
280
320
360
400
Glu
co
se (
mg
/dL
)
Date: 29-Sep-2014
00:00 02:00 04:00 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:000123456789
101112131415
Infu
sio
n R
ate
(U
/h)
Clock (HH:MM)
UVA DiAs Ambulatory Closed-Loop System Overnight camp study
Ly, Diab Care 2014
• N=20, 5-6 nights
![Page 11: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/11.jpg)
Del Favero, Diab Care 2014
Outpatient Full-Day Hybrid Closed-Loop
• N=6, 28 hr on CL
Boston University Dual-Hormone Delivery System with Insulin And Glucagon
Hybrid Closed-Loop – multiple hormone
(glucagon) plus standardized pre-meal bolus
Russell, Diab Care 2012• N=6, 48 hr
Bi-Hormonal Delivery in
20 Adults & 32 Adolescents
Russell SJ et al. N Engl J Med 2014;371:313-325
![Page 12: l Research and Grant Support to Employer: Future ...diabetesatlanta.org/web/wp-content/uploads/2014/11/... · Insulin Suspends for 2 hours / Resumes for 4 hours ... (p](https://reader036.fdocuments.us/reader036/viewer/2022081614/5fc34bc9d408cd649f145db4/html5/thumbnails/12.jpg)
Full Closed-Loop – multiple hormone
(pramlintide) without meal bolus
Palau-Collazo, ADA 2013
6 9 12 15 18 21 24 27 30 330
100
200
300
Pramlintide
Control
Time (hrs)
Blo
od
G
luco
se (
mg
/dL
)
• N=10, 48 hr
Conclusions
• Sensor-augmented pump systems are becoming increasingly integrated and incrementally more automated
• Hybrid closed-loop systems with meal bolus requirements will soon be market-ready
• Fully-automated single- or multiple-hormone systems are in pipeline but more distant in product development and/or regulatory approval