New Insulins and Insulin Delivery Systems Bruce W. Bode, MD, FACE Atlanta Diabetes Associates Atlanta, Georgia
Dec 26, 2015
New Insulins and
Insulin Delivery Systems
Bruce W. Bode, MD, FACE
Atlanta Diabetes Associates
Atlanta, Georgia
Methods For Managing Persons with Diabetes
Take Diabetes out of the equation.
Control glucose!!!
Undiagnosed diabetes
~5.2 million
Prevalence of Glycemic Abnormalities in the United States
Additional 25 -35 million
with Prediabetes
Diagnosed type 2 diabetes
~12 million
Diagnosed type 1 diabetes
~1.0 million
Centers for Disease Control. Available at: http://www.cdc.gov/diabetes/pubs/estimates.htm; Harris MI. In: National Diabetes Data Group. Diabetes in America. 2nd ed. Bethesda, Md: NIDDK; 1995:15-36; U.S. Census Bureau Statistical Abstract of the U.S.; 2001
US Population: 275 Million in 2000
3
Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.
Diabetes Care. 2001;24(Suppl 1):S5-S20.
FPG
126 mg/dL
100 mg/dL
7.0 mmol/L
5.6 mmol/L
Prediabetes
NormalNormal
2-Hour PG on OGTT
200 mg/dL
140 mg/dL
11.1 mmol/L
7.8 mmol/L
Diabetes MellitusDiabetes Mellitus
Impaired Glucose Tolerance
NormalNormal
Diabetes MellitusDiabetes Mellitus
Diagnostic Criteria Associated with Glucose Abnormalities
Relative Risk of Progression of Diabetes Complications (DCCT)
DCCT Research Group, N Engl J Med 1993, 329:977-986.
1
3
5
7
9
11
13
15
6 7 8 9 10 11 12
Retinop
Neph
Neurop
RELATIVE RISK
Mean A1C
Gain of 15.3 years of complication free living compared to conventional therapy
Gain of 5.1 years of life compared to conventional therapy
Lifetime Benefits ofIntensive Therapy (DCCT)
DCCT Study Group, JAMA 1996, 276:1409-1415.
Effect of A1C On Complications in the UKPDS Study
A1C
Stratton IM et al. BMJ 2000;321:405
0
10
20
30
40
50
60
Myocardial Infarction Microvasc Disease
5.5%6.5%7.5%8.5%9.5%10.5%
Lessons from the DCCT and UKPDS:Lessons from the DCCT and UKPDS:Sustained Intensification of Therapy is DifficultSustained Intensification of Therapy is Difficult
DCCT EDIC(Type 1)
UKPDS (Type 2),Insulin Group
DCCT/EDIC Research Group. New Engl J Med 2000; 342:381-389Steffes M et al. Diabetes 2001; 50 (suppl 2):A63UK Prospective Diabetes Study Group (UKPDS) 33Lancet 1998; 352:837-853
4
6
8
10
9.0
8.1
7.3
7.9
0 6.5 + 4 + 6 yrs
DCCT EDIC
0
6
7
8
0 2 4 6 8 10 yrs
A1C (%)
Normal
Baseline
A1C (%)
Specific Goals in Management of Diabetes
Fasting < 110 mg/dL
Post-meal < 140 mg/dL
A1C < 6.5%
Blood Pressure < 130/80
LDL < 100 mg/dL; HDL > 45 mg/dL
Triglycerides < 150 mg/dL
Primary Objectives of Effective Management
A1C%
SBPmm Hg
LDLmg/dL
45 50 55 60 65 70 75 80 85 90
9
Diagnosis
8
7
130
100
145
140
Patient Age
Reduction of both
micro- and macro-vascular
event rates
…by 75%!
lGæde P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl
J Med. 2003;348:383-393.
0
2
4
6
8
10
12
14
16
<150 150-175 175-200 200-225 225-50 >250
Average Post-operative glucose (mg/dl)
Mo
rtali
ty
Cardiac-related mortalityNoncardiac-related mortality
Mortality of DM Patients Undergoing CABG
Furnary et al J Thorac Cardiovasc Surg 2003;123:1007-21
0
5
10
15
20
25
30
35
40
45
0 50 100 150 200 250
Days after inclusion
Cum
ulat
ive
% M
orta
lity
(in h
ospi
tal d
eath
)
P=0.0009
P=0.026
BG<110
110<BG<150
BG>150
Surgical ICU MortalityEffect of Average BG
Van den Berghe et al (Crit Care Med 2003; 31:359-366)
05
1015202530354045
80-99 100-119
120-139
140-159
160-179
180-199
200-249
250-299
>300
Average ICU glucose (mg/dl)
Mo
rtal
ity
%
Hyperglycemia and Hospital Mortality1826 consecutive ICU patients 10/99 thru 4/02, Stamford CT
Krinsley JS: Mayo Clin Proc 78: 1471-1478, 2003
Glucose Goals in Type 2 DiabetesGlucose Goals in Type 2 Diabetes
• Fasting < 110 mg/dL
• Post-meal < 140 mg/dL
• A1C < 6.5%
Glucose Goals in Type 1 DiabetesGlucose Goals in Type 1 Diabetes
• Fasting and Premeal 70 - 140 mg/dL
• Post-meal < 160 mg/dL
• A1C < 6.5%
Glucose Goals in Hospital
80 – 110 mg/dl in Surgical ICU patients
80 - 140 mg/dl premeal and < 180 mg/dl postmeal in other Surgical and Medical Patients
70 – 100 mg/dl in Pregnancy
Insulin
The most powerful agent we have
to control glucose
Patient J.L., December 15, 1922 February 15, 1923
The Miracle of Insulin
Progression of Type 1 Diabetes
Adapted from: Atkinson. Lancet. 2002;358:221-229.
Age (y)
Precipitating Event
Be
ta-c
ell
ma
ss
Genetic predisposition
Normal insulin release
Glucose normal
Overt diabetes
No C-peptidepresent
Progressive loss of insulin release
C-peptidepresent
AntibodyAntibody
Options in Insulin Therapy for Type 1 Diabetes
Current
– Multiple injections
– Insulin pump (CSII)
Future
– Implant (artificial pancreas)
– Transplant (pancreas; islet cells)
Type 2 Diabetes … A Progressive Disease
Over time, most patients will need insulin
to control glucose
Multiple factors may drive progressive decline of -cell function
-cell(genetic background)
Hyperglycaemia(glucose toxicity)
Proteinglycation
Amyloiddeposition
Insulin resistance
“lipotoxicity”elevated FFA,TG
Approach to Combination Oral Therapy
Intensifying of Oral Therapies
metformin &/or glitazone+
sulfonylurea/repaglinide&/or glucosidase inh
sulfonylurea/repaglinide&/or glucosidase inh
+metformin &/or glitazone
Continue
FPG < 120 mg/dl A1C < 6.5% FPG > 120 mg/dl A1C >6.5%
Add Insulin
Comparison of Human Insulins / Analogues
Insulin Onset of Duration ofpreparations action Peak action
Regular 30–60 min 2–4 h 6–10 h
Lispro/aspart 5–15 min 1–2 h 4–6 h
NPH/Lente 1–2 h 4–8 h 10–20 h
Ultralente 2–4 h Unpredictable 16–20 h
Glargine 1–2 h Flat ~24 h
Dissociation & Absorption of Aspart / Lispro
Insulin Aspart or Lispro
Regular Human Insulin
Peak Time = 80-120 min
Peak Time = 40-50 min
CapillaryMembrane
Su
bcu
tan
eou
s T
issu
eS
ub
cuta
neo
us
Tis
sue
400
350
300
250
200
150
100
MealSC injection
50
00 30 60
Time (min)90 120 180 210150 240
Regular Lispro
500450400350300250
150
50
200
100
00 50 100
Time (min)150 200 300250
Pla
sm
a i
ns
uli
n (
pm
ol/
L)
Pla
sm
a i
ns
uli
n (
pm
ol/
L)
MealSC injection
Heinemann, et al. Diabet Med. 1996;13:625–629; Mudaliar, et al. Diabetes Care. 1999;22:1501–1506.
Short-Acting Insulin AnalogsLispro and Aspart Plasma Insulin Profiles
Regular Aspart
Lepore, et al. Diabetes. 1999;48(suppl 1):A97.
6
5
4
3
2
1
00 10
Time (h) after SC injection
End of observation period
20 30
GlargineNPH
Glu
cose
uti
lizat
ion
rat
e(m
g/k
g/h
)
Glargine vs NPH Insulin in Type 1 DiabetesAction Profiles by Glucose Clamp
4:004:00
2525
5050
7575
8:008:00 12:0012:00 16:0016:00 20:00 20:00 24:0024:00 4:004:00
BreakfastBreakfast LunchLunch DinnerDinner
Pla
sma
insu
lin
(P
lasm
a in
suli
n (µ U
/ml)
U
/ml)
TimeTime
8:008:00
Physiological Serum Insulin Secretion Profile
4:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
8:0012:008:00
Time
Glargine
Lispro Lispro Lispro
Aspart Aspart Aspartor oror
Pla
sma
insu
lin
Basal/Bolus Treatment Program withRapid-acting and Long-acting Analogs
The Basal/Bolus Insulin Concept
Basal insulin
– Suppresses glucose production between meals and overnight
– 40% to 50% of daily needs
Bolus insulin (mealtime)
– Limits hyperglycemia after meals
– Immediate rise and sharp peak at 1 hour
– 10% to 20% of total daily insulin requirement at each meal
Insulin Therapy in Type 2 Diabetes Indications
Significant hyperglycemia at presentation Hyperglycemia on maximal doses of oral agents Decompensation
– Acute injury, stress, infection, myocardial ischemia– Severe hyperglycemia with ketonemia and/or ketonuria– Uncontrolled weight loss– Use of diabetogenic medications (eg, corticosteroids)
Surgery Pregnancy
Starting With Basal Insulin in DM 2Advantages
1 injection with no mixing
Insulin pens for increased acceptance
Slow, safe, and simple titration
Low dosage
Effective improvement in glycemic control
Limited weight gain
6-37
Treatment to Target Study: NPH vs Glargine in DM2 patients on OHA
Add 10 units Basal insulin at bedtime (NPH or Glargine)
Continue current oral agents
Titrate insulin weekly to fasting BG < 100 mg/dL
- if 100-120 mg/dL, increase 2 units
- if 120-140 mg/dL, increase 4 units
- if 140-180 mg/dL, increase 6 units
- if >180 mg/dL, increase 8 units
Treatment to Target Study; A1C Decrease
8.6
7.5
7.16.9 7
6.5
7
7.5
8
8.5
9
0 5 10 15 20 25 30
Weeks in Study (N=691)
Mea
n H
bA
1c%
Treatment to Target Study: % at Goal
57% of patients in both groups reached A1C 7%
At wk 24, mean insulin glargine dose was higher than mean NPH insulin dose:
Insulin glargine NPH insulin
48.8 IU/day 42.4 IU/day , P<0.001
Rosenstock J, Riddle M, HOE901/4002 Study Group. Diabetes 2002;51(suppl 2):A482. Abstract 1982-PO
Results
Treat to Target Study: Glargine vs NPH Added to Oral Therapy of Type 2 Diabetes
Nocturnal Hypoglycemia reduced by 40% in the Glargine group (532 events) vs NPH group (886 events)
Riddle et al, Diabetes June 2002, Abstract 457-p
Morning vs Bedtime InsulinMorning vs Bedtime Insulin
Baseline: 9.11.0
Morning Glargine
Bedtime Glargine
Bedtime NPH
-2
-1
0
A1C
Ch
ang
e F
rom
B
asel
ine
(%)
–1.24
–0.96–0.84
P<0.001
P=0.008
Adapted from Fritsche A et al, and the 4001 Study Group. Ann Intern Med. 2003:138:952
Starting with Bolus Insulin
16 obese Type 2 patients on NPH or Human 70/30 insulin twice daily randomized to:
Insulin aspart premeal with metformin and rosiglitazone
NPH or Human 70/30 twice daily
Insulin titrated to 90 to 126 mg/dl at 1.5 hr post meal in the aspart group and premeal in the conventional group with goal A1C <7%
Diabetes Care 2003
Insulin Aspart Premeal with Metformin and Rosiglitazone vs Conventional Insulin
5
6
7
8
9
10
Insulin Aspart Premeal NPH or 70/30 BID
Baseline
6 months
A1C%
N =16
0.42 units/kg
3 kg weight gain
0.67 units/kg
1 kg weight gain
P = 0.03
Advancing Basal/Bolus Insulin
Indicated when FBG acceptable but– A1C > 7% or > 6.5%
and/or– SMBG before dinner > 140 mg/dL
Insulin options– To glargine or NPH, add mealtime aspart / lispro– To suppertime 70/30, add morning 70/30– Consider insulin pump therapy
Oral agent options– Usually stop sulfonylurea– Continue metformin for weight control– Continue glitazone for glycemic stability?
Novo Nordisk devices in diabetes care
First pen (NovoPen 1) launched in 1985
Committed to developing one new insulin administration system per year.
Lilly Insulin Pens
Prefilled Syringe with Flexible Dosing
82%
2%
16%
Prefer FlexPen
Prefer Humalog pen
No preference
82% of DNEs Preferred FlexPen®
Source: Diabetes Nurse Educators In-Depth Study—Reactions to FlexPen.
NovoLog® FlexPen®
®
Novo Innolet®
Large push button with low resistance
Large-scale numbers
1 unit increments
Support shoulder
Maximum dose 50 units
Clear & uncomplicated dial, dials forward and back
Contains 300 units Novolin® 70/30, NPH, or R
Audible clicks
NovoFine® disposable needle
Needle storage compartment
Starting MDI
Starting insulin dose is based on weight
0.2 x wgt. in lbs. or 0.45 x wgt. in kg
Bolus dose (aspart/lispro) = 20% of starting dose at each meal
Basal dose (glargine/NPH) = 40% of starting dose at bedtime
Starting MDI in 180 lb person
Starting dose = 0.2 x wgt. in lbs.
0.2 x 180 lbs. = 36 units
Bolus dose = 20% of starting dose at each meal
20% of 36 units = 7 units ac (tid)
Basal dose = 40% of starting dose at bedtime
40% of 36 units = 14 units at HS
Individually determined
CIR = (2.8 x wgt in lbs) / TDD
Anywhere from 5 to 25 g CHO is covered by 1 unit of insulin
Estimating the Carbohydrate to Insulin Ratio (CIR)
Correction Bolus (Supplement)
Must determine how much glucose is lowered by 1 unit of short- or rapid-acting insulin
This number is known as the correction factor (CF)
Use the 1700 rule to estimate the CF
CF = 1700 divided by the total daily dose (TDD)
ex: if TDD = 36 units, then CF = 1700/36 = ~50
meaning 1 unit will lower the BG ~50 mg/dl
Correction Bolus Formula
Example:
–Current BG: 220 mg/dl
– Ideal BG: 100 mg/dl
–Glucose Correction Factor: 50 mg/dl
Current BG - Ideal BGGlucose Correction factor
220 - 100 50
=2.4u
Options to MDI
A Simpler Regimen
Insulin Pump
Premixed BID (DM 2 only)
Human Insulin Time-action Patterns
Time (h)
Baseline
level
Regular insulin
Premix 70/30
SC injection
Normal insulin secretionat mealtime
NPH insulin
Ch
ang
e in
ser
um
in
suli
n
A More Physiologic Insulin
Time (h)SC injection
Baseline
Level
Normal insulin secretion at mealtime
NPH insulin
NovoLog
NovoLog Mix 70/30
Ch
an
ge
in s
eru
m in
su
lin
Analog Mix 70/30: Serum Insulin Levels in Type 2 Diabetes
Breakfast Lunch
06:00 PM 10:00 PM 8:00 AM 6:00 PM1:00 PM
Dinner
Cmax
Se
rum
ins
ulin
(m
U/L
)
100
Time
80
40
20
60
* * NovoLog® Mix 70/3070/30 Premix
McSorley. Clin Ther. 2002;24(4):530-539.
*P<0.05.
Analog Mix 70/30 vs 75/25 vs 70/30 Premix: Serum Insulin Levels in Type 2 Diabetes
Lispro Mix 75/25
70/30 Premix
Aspart Mix 70/30
0 1 2 3 4 50
80
Time (h)
Se
rum
ins
ulin
(m
U/L
)
60
40
20
Hermansen. Diabetes Care. 2002;25(5):883-888.
Aspart Mix 70/30:Serum Glucose Levels in Type 2 Diabetes
Aspart Mix 70/3070/30 Premix
Dinner Breakfast Lunch
*
0
300
200
150
250
Se
rum
glu
co
se (
mg
/dL
)
6:00 PM 10:00 PM 8:00 AM 6:00 PM1:00 PM
**
*Glucose excursions 0-4 h, P<0.05.McSorley. Clin Ther. 2002;24(4):530-539.
4:004:00 16:0016:00 20:00 20:00 24:0024:00 4:004:00
BreakfastBreakfast LunchLunch DinnerDinner
8:008:0012:0012:008:008:00
TimeTime
Basal infusion
Bolus Bolus Bolus
Pla
sma
insu
lin
Pla
sma
insu
lin
Variable Basal Rate: CSII Program
Photograph reproduced with permission of manufacturer.
Pump Infusion Sets
CSII vs MDI in 100 DM 1 Patients
Bode, et al. Diabetes 52,(Suppl 1), 2003 Abstract 438.
Mean ± 2 SEM
200
160
140
120
100
180
Se
lf-m
on
ito
red B
G (
mg
/dL
)
BB AB BL AL BD AD Midnight 3 AM
CSII (n=93)
MDI (n=91)
n=63 in each treatment
0
500
1000
1500
2000
2500
3000
CSII MDI
p = 0.0027
Novo Nordisk, data on file (Study 2155/US)
Aspart (CSII) vs Aspart/Insulin glargine (MDI) Glucose Exposure During CGMS
Measurement of AUC(glu) ≥80 mg/dL during the 48-hour continuous glucose monitoring period
†
AUCglu (mg•hr/dL)
†
6
6.5
7
7.5
8
8.5
9
Baseline 4 weeks 8 weeks 12 weeks 16 weeks
Glargine (n=16)
CSII (n=14)
CSII vs. MDI with Glargine in Children (Preliminary Data)
Boland, E. Diabetes 52,(Suppl 1), 2003 Abstract 192.
A1c
CSII vs MDI in Children – Preliminary Data Safety and Preference
SafetySevere hypoglycemic episodes
MDI: 4CSII: 2
No cases of DKA
Preference (at 16 weeks)All 12 CSII subjects remained on CSII12 of 14 MDI subjects switched to CSII
Boland et al., Diabetes 2003, 52:S1, A45, 192-OR
CSII vs MDI with NPH in 127 DM 2 Patients
7.0
7.2
7.4
7.6
7.8
8.0
8.2
8.4
CSII MDI
Baseline
End of study (24 weeks)
Raskin et al. Diabetes Care Sept 2003
A1C
(%
)
Change in scores (raw units) from baseline to endpoint
-5 0 5 10 15 20 25 30 35
Convenience
Less burden
Less hassle
Advocacy
Preference
General satisfaction
Flexibility
Less life interference
Less pain
Fewer social limitations
MDICSII
CSII vs MDI in DM 2 Patients
Testa et al. Diabetes. 2001;50(suppl 2):1781
Current Pump Therapy Indications
Diagnosed with diabetes (even new onset DM 1)
Need to normalize blood glucose (BG)
–A1C > 6.5%
–Glycemic excursions
Hypoglycemia
Monitoring– A1C = 8.3 - (0.21 x BG per day)
Recording 7.4 vs 7.8
Diet practiced– CHO: 7.2– Fixed: 7.5– WAG: 8.0
Insulin type (Aspart)
CSIIFactors Affecting A1C
Bode et al. Diabetes 1999;48 Suppl 1:264
Bode et al. Diabetes Care 2002;25 439
• Total Daily Dose = 0.23 x Wgt. In lbs.
• Basal Dose = 0.47 x Total Daily Dose
• CIR = (2.8 x Wgt in lbs) / TDD
(Anywhere from 5 to 25 g CHO is covered by 1 unit of insulin)
• Correction Factor = 1700 / TDD
• Target = 100 mg/dl
Pump Formulas
Davidson et al: Diabetes Tech & Therap. April 2003
Individually determined
• CIR = (2.8 x wgt in lbs) / TDD
• Anywhere from 5 to 25 g CHO is covered by 1 unit of insulin
Estimating the Carbohydrate to Insulin Ratio (CIR)
Davidson et al: Diabetes Tech & Therap. April 2003
Bolus: Source of Errors
“Inability” to count carbs correctly
– Lack of knowledge, skill
– Lack of time
– Too much work
Incorrect use of SMBG number
Incorrect math in calculation
“WAG” estimations
Most common bolusing errors
Under-estimation of carbohydrates consumed (CHO bolus)
Over-correction of post-prandial elevations (CF bolus)
– Remaining unused, active insulin
– Stacking of boluses
The Major Problems
♦ Up until now we have not taken the active insulin issue into consideration
♦ The math involved with this has become too complicated, and it would be impossible to accurately calculate the active insulin without assistance
Smart Insulin PumpsSmart Insulin Pumps
Monitor sends BG value to pump via radio waves : No transcribing error
Enter carbohydrate intake into pump
“Bolus Wizard” calculates suggested dose
Paradigm Link™
Paradigm 512™) ) ) ) ) ) ) ) ) )
) ) )
Bolus Wizard Calculator : meter-entered
For This System To Work
♦ It is critical the target, basal doses, the correction doses, and the carbohydrate ratios are accurate
♦ Understanding how to match carbohydrate amounts with insulin is critical
♦ If the target is set too high (>110 mg/dl), glucoses will run too high. Normal target is 100 mg/dl and for pregnancy 80 mg/dl is safe.
Do Smart Pumps Enable Others To Go To CSII?
YES
All patients with diabetes not at goal are candidates for Insulin Pump Therapy
- Type 1 any age
- Type 2
- Diabetes in Pregnancy
If A1C is Not to Goal
SMBG frequency and recording
Diet practiced
– Do they know what they are eating?
– Do they bolus for all food and snacks?
Infusion site areas
– Are they in areas of lipohypertrophy?
Other factors:
– Fear of low BG
– Overtreatment of low BG
Must look at:
If A1C Not to Goal and No Reason Identified
Place on a continuous glucose monitoring system (CGMS by Medtronic Minimed, Glucowatch by Cygnus) to determine the cause
CGMS
CGMS Sensor
GLUCOSE MONITORING SYSTEMS - Telemetry
“Real time” glucose readings
Wireless communication from sensor to monitor
High and low glucose alarms
FDA panel pending
Consumer Product
GlucoWatch® Biographer
FreeStyle NavigatorTheraSense Continuous Glucose Monitor
• Patient Inserted Sensor
• “On demand” glucose and trend arrow
• User-configurable Low Glucose and High Glucose Alarms
• Projected alarms give advance warning of glucose excursions
• Integrated FreeStyle blood glucose meter
• (3) BG calibrations for each 3-day sensor
• Wireless sensor-to-Meter path (10 foot operating range)
FreeStyle NavigatorTheraSense Continuous Glucose Monitor
–Designed to monitor interstitial fluid and provide continuous glucose readings–Patient-attached adhesive section includes sensor, and wireless transmitter–Designed to be self-inserted every three days and provide patients with glucose for use in managing therapy
The DexCom Continuous Glucose Sensor System
Sensor
– 7 x 1 cm
– Cylindrical
– 7 cc
– Battery
– Microprocessor
– Antenna
Receiver
– Pager-Like Receiver with Graphical Display
Implantable Pump
Average HbA1c 7.1%
Hypoglycemic events reduce to 4 episodes per 100 pt-years
Implanted Closed-Loop External Closed-Loop
Vision towards the Artificial Pancreas
* This product concept not yet submitted to the FDA for commercialization.
Predicted Times
Glucose Sensors
- Alarm sensor (72 hr) early 2004
- Replace fingersticks mid late 2005
Semi-Closed loop 2006 – 2007
Implantable 2007-2008
Summary
Insulin remains the most powerful agent we have to control diabetes
When used appropriately in a basal/bolus format, near-normal glycemia can be achieved
Newer insulins and insulin delivery devices along with glucose sensors will revolutionize our care of diabetes
Billing Get paid for what you do
Use your codes and negotiate for coverage
Detailed visit: 99214
Prolonged visit with contact plus above: 99354 or 99355
(insulin start or pump start)
Prolonged visit w/o contact plus above:
99358 or 59 (faxes, phone calls, emails)
Billing
Bill faxes as prolong visits with out contact or negotiate a separate charge
Bill meter download: 99091
Bill CGMS: 95250
Bill immediate A1C: 83036
Questions
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