Download Concentrate! Key Takeaways of new insulin products

CONCENTRATE!
KEY TAKEAWAYS OF NEW INSULIN
PRODUCTS
Sara Wettergreen, PharmD, BCACP
Assistant Professor of Pharmacotherapy
University of North Texas System College of Pharmacy
Learning Objectives: Pharmacists
•
Compare and contrast use of insulin pen devices
•
Identify patients who may benefit from use of new insulin products
•
Design a patient-specific treatment regimen using new insulin products
Learning Objectives: Technicians
•
Compare and contrast use of insulin pen devices
•
Define safety considerations related to insulin use
•
Assist patients with obtaining pricing discounts for new insulin products
Diabetes: A Growing Problem
• 29.1 million people in the
United States have diabetes
• About 1 in 4 of these are
undiagnosed
• 37% of patients treated for
diabetes use insulin
Center for Disease Control (CDC). National diabetes statistics report, 2014.
“Egregious Eleven”
Schwartz et al. Dia Care 2016;39:179-186
Role of Insulin
American Diabetes Association Dia Care 2016;39:S52-S59
Role of Insulin
Reprinted with permission from American Association of Clinical
Endocrinologists © 2016 AACE. Endocr Pract.2016;22: 84-113.
New Insulin Products
•
Insulin glargine U-100 equivalent (Basaglar®)
•
Became available December 15th, 2016
•
Insulin glargine U-300 (Toujeo®)
•
Insulin degludec U-100 and U-200 (Tresiba®)
•
Regular human insulin u-500 (Humulin R U-500 KwikPen®)
•
Insulin lispro U-200 (Humalog U-200 KwikPen®)
www.accessdata.fda.gov/Scripts/cder/drugsatfda/ .
Characteristics of an Ideal Basal Insulin
• PK/PD profile that more closely mimics endogenous basal insulin secretion
• Low risk of hypoglycemia
• Minimal weight gain
• Dosing flexibility
• Easy for patients to administer
Advances with Basal Insulins
Detemir
Glargine U-100
Glargine U-100
equivalent
NPH
•
•
•
Peak
Shorter duration
Risk of hypoglycemia
•
•
•
Glargine U-300
Degludec U-100, U-200
•
•
•
Less peak
Longer duration
Lower risk of hypoglycemia
Less peak
Longer duration
Lower risk of hypoglycemia
Insulin Glargine U-100 Equivalent (Basaglar®)
•
Not considered a “biosimilar” as the Biologic
License Application (BLA) pathway was not
used, but is a follow-on biologic approved via
the New Drug Application (NDA) pathway
•
Conversion from insulin glargine U-100
(Lantus®) is 1:1 dose
•
Non-inferior to insulin glargine U-100 (Lantus®)
Basaglar [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company.
Rosenstock J, et al. Diabetes Obes Metab. 2015;17(8):734-741.
Insulin Glargine U-300 (Toujeo®)
Volume
•
FDA approved February 2015
•
Available in disposable, prefilled SoloSTAR
pen device
•
1/3 of injection volume compared with U-100
•
Reduces depot surface area by ½
•
Surface Area
Allows for a gradual, prolonged rate of absorption
•
Each pen contains 450 units
•
Maximum single injection dose = 80 units
U-100
TOUJEO® (insulin glargine) injection 300 units/mL [prescribing information].
Bridgewater, NJ: Sanofi-Aventis.
U-300
Insulin (µU/mL)
PK/PD of Insulin Glargine U-300 vs. U-100
30
20
10
0
0
1
2
3
4
5
6
7
8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
Time (hours)
GIR (mg/kg/min)
U-100
U-300
3
2
1
0
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
Time (hours)
U-100
Becker RHA. Diabetes Care 2015;38:637-43.
U-300
EDITION 1: Insulin Glargine U-300
Multicenter, open-label
T2D patients, A1C 7%–10%
Current basal therapy with ≥ 42 units/day of
glargine or NPH + mealtime RAIA ± metformin
Insulin glargine U-100
Once daily using pen device
Adjusted no more than every 3 days to
goal FPG 80–100 mg/dL
Insulin glargine U-300
Once daily using pen device
Adjusted no more than every 3 days to
goal FPG 80–100 mg/dL
Primary Outcome: A1C change from baseline to month 6
Riddle MC. Diabetes Care 2014;37:2755-62.
EDITION 1: Insulin Glargine U-300
Outcome
Glargine U-300
(n=404)
Glargine U-100
(n=403)
Change in A1C from baseline (%)
-0.83
-0.83
Change in weight from baseline (kg)
+0.9
+0.9
Daily basal insulin dose at end of
study (units)
103
94
Confirmed or severe nocturnal
hypoglycemic events (%)
36
46
Met predefined noninferiority criteria.
Riddle MC. Diabetes Care 2014;37:2755-62.
EDITION 2: Insulin Glargine U-300
Multicenter, open-label
T2D patients, A1C 7%–10%
Current basal therapy with ≥ 42 units/day of
glargine or NPH + OADs
Insulin glargine U-100
Once daily using pen device
Adjusted no more than every 3 days to
goal FPG 80–100 mg/dL
Insulin glargine U-300
Once daily using pen device
Adjusted no more than every 3 days to
goal FPG 80–100 mg/dL
Primary Outcome: A1C change from baseline to month 6
Yki-Jarvinen H. Diabetes Care 2014;37:3235-43.
EDITION 2: Insulin Glargine U-300
Outcome
Glargine U-300
(n=404)
Glargine U-100
(n=407)
Change in A1C from baseline (%)
-0.57
-0.56
Daily basal insulin dose at end of
study (units)
91
82
Nocturnal hypoglycemic (%)
30.5
41.6
Confirmed or severe
hypoglycemia (%)
21.6
27.9
Met predefined noninferiority criteria.
Yki-Jarvinen H. Diabetes Care 2014;37:3235-43.
EDITION 3: Insulin Glargine U-300
Multicenter, open-label
T2D patients, A1C 7%–11%
Insulin naive using OADs
Insulin glargine U-100
Once daily using pen device
Adjusted no more than every 3 days to
goal FPG 80–100 mg/dL
Insulin glargine U-300
Once daily using pen device
Adjusted no more than every 3 days to
goal FPG 80–100 mg/dL
Primary Outcome: A1C change from baseline to month 6
Bolli GB. Diabetes Obes Metab 2015;17:386-94.
EDITION 3: Insulin Glargine U-300
Outcome
Glargine U-300
(n=439)
Glargine U-100
(n=439)
Change in A1C from
baseline (%)
-1.42
-1.46
Daily basal insulin dose
at end of study (units)
59.4
52
Nocturnal confirmed or
severe hypoglycemic (%)
18
24
Met predefined noninferiority criteria.
Bolli GB. Diabetes Obes Metab 2015;17:386-94.
Insulin Glargine U-300: Summary
•
Smoother PK/PD profile than glargine U-100
•
Full 24-hour coverage; flexibility in dosing time
•
Less nocturnal hypoglycemia than glargine U-100
•
Smaller injection volume
•
1:1 conversion recommended when switching from glargine U-100
•
Higher doses (~10%) may be needed compared with insulin glargine U-100
TOUJEO® (insulin glargine) injection 300 units/mL [prescribing information].
Bridgewater, NJ: Sanofi-Aventis.
Insulin Degludec (Tresiba®)
•
Approved by FDA September 25, 2015
•
U-100 (Tresiba® 100 units/mL)
• FlexTouch pen device
• 300 units per pen; max single dose = 80 units
• Duration of action > 40 hours; allows for flexibility in dosing
• Doses are selected in 1 unit increments
•
U-200 (Tresiba® 200 units/mL)
• FlexTouch pen device; low volume
• 600 units per pen, max single dose = 160 units
• Bioequivalent to degludec U-100; similar glucose lowering
• Doses are selected in 2 unit increments
Zinman B. Diabetes Care 2012;35:2464-71; Gough SC. Diabetes Care 2013;36:2536-42
Garber AJ. Lancet 2012;379:1498-507.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm464321.htm
Insulin Degludec PK/PD
•
Half life >25 hours
•
Duration of action: 42 hours
•
Steady state is reached within 3
days, thus dose titrations should
occur on a weekly basis
•
Similar PK/PD between the U-100
and U-200 concentrations
Vora J, et al. Diabetes Research in Clinical Practice 2015;109:19-31.
Insulin Degludec
Confirmed or
Severe
Nocturnal
Hypoglycemia
(per pt-year)
Clinical Trial
(Duration)
Background
Therapy
Comparator
Arms
Change in
A1C (%)
End of Trial
Insulin Dose
(units/kg)
Hypoglycemia
(episodes
per pt-year)
Zinman
(52 weeks)
Metformin
(insulin naive)
IDeg U-100
-1.06
0.59
1.52
0.25*
Glargine
-1.19
0.60
1.85
0.39
IDeg U-100
-1.1
0.75
11.1*
1.4*
Glargine
-1.2
0.69
13.6
1.8
IDeg U-200
-1.22
0.53*
1.22
0.18
Glargine
-1.42
0.60
1.42
0.28
Garber
(52 weeks)
Insulin ± OADs
Gough
(26 weeks)
Metformin ±
DPP-4i
(insulin naive)
Noninferiority criteria met.
*p<0.05.
Zinman B. Diabetes Care 2012;35:2464-71; Gough SC. Diabetes Care
2013;36:2536-42; Garber AJ. Lancet 2012;379:1498-507.
Converting to Insulin Degludec
Vora J, et al. Diabetes Research in Clinical Practice 2015;109:19-31.
Patient Considerations with Insulin Degludec
• Titration Frequency
TITRATE Study: Insulin determir was
titrated by 3 units every 3 days
• Titrations with insulin degludec should
be made on a weekly basis due to the
extended duration of action
•
• Adherence
Flexibility in timing between doses
with a minimum of 8 hours between
doses
• Minimal change is safety or efficacy
with variability in timing of doses
between 8 to 40 hours between doses
•
Vora J, et al. Diabetes Research in Clinical Practice 2015;109:19-31.
Insulin Degludec: Summary
•
Extended duration of action compared to other basal insulin products
•
Less nocturnal hypoglycemia with degludec U-100 than glargine U-100
•
1:1 conversion recommended when switching from other basal insulins
•
•
20% dose reduction may be considered if using twice daily dosing
Extended coverage; flexibility in dosing time; weekly titrations
Vora J, et al. Diabetes Research in Clinical Practice 2015;109:19-31.
Regular Human Insulin U-500 (Humulin R U-500 KwikPen®)
• Nothing new about the insulin
Five times as concentrated as U-100 insulin
• Used for severe insulin resistance (total daily dose >200 units/day)
•
• The PEN is new!
1500 units per 3 mL pen
• Doses are selected in 5 unit increments
• No dose-conversions needed (compared to vial use)
•
Humulin R U-500 KwikPen [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company.
Regular Human Insulin U-500
• Continues to be available in a 20 mL vial (10,00 units of insulin)
• U-500 syringe is recommended for use with the U-500 vial
Humulin R U-500 [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company.
Regular Human Insulin U-500: Dosing Review
•
Conversion from U-100 products to U-500
•
•
•
A1c ≥ 8%: 1:1 conversion from U-100 to U-500 insulin total daily dose (TDD)
May decrease TDD by 10-20% if A1c<8%
The TDD is then divided
Required TDD
(Units)
Route and Frequency
U-500 Insulin Dosage
150-300
Twice daily
50/50 or 60/40 before breakfast and supper
Three times daily
33/33/33 before meals
Three times daily
33/33/33 before meals
Four times daily
30/30/30/10 (mealtimes and bedtime)
Four times daily
30/30/30/10 (mealtimes and bedtime)
300-600
>600
Segal AR, et al. Am J Health-Syst Pharm. 2010; 67:1526-35
Regular Human Insulin U-500: Dose Titration
Ballani P, et al. Diabetes Care. 2006; 29(11):2504-2505.
Characteristics of an Ideal Bolus Insulin
• Low risk of hypoglycemia
• Minimal weight gain
• Dosing flexibility
• Easy for patients to administer
Advances with Bolus Insulins
Rapid-acting
insulin analogs
Regular
•
•
•
Slow onset
Longer duration
Risk of hypoglycemia
•
•
•
•
Faster onset
Shorter duration
Clinical outcomes
Pen devices
Lispro U-200
• Decreased number of pens
needed with high doses
• Pen device
Insulin Lispro U-200 (Humalog U-200 KwikPen®)
• The CONCENTRATION is new!
Twice as concentrated as U-100 insulin
• 1500 units per 3 mL pen
• Doses are selected in 1 unit increments
• 1:1 unit conversion recommend when switching
from insulin lispro U-100
• Benefit is that patients on high bolus doses will
use less pens
•
Humalog [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company.
http://www.humalog.com/humalog-u200-hcp.aspx
Ultra-Rapid Acting Insulin Aspart (NN1218)
• Earlier time to 50% maximal concentration
•
Faster-acting insulin aspart: 20.7 minutes
•
Insulin aspart: 31.6 minutes
•
Application submitted to the FDA
•
October 7, 2016 – FDA response letter issued requesting additional
information for the immunogenicity and clinical pharmacology data
Heise T, et al. Diabetes Obes Metab. 2015;17(7):682-688
http://www.novonordisk.com/media/news-details.2047717.html
Discussion Question!
What patients may be good candidates for each of these new
insulin products?
•
Insulin glargine U-300 (Toujeo®)
•
Insulin degludec U-100 and U-200 (Tresiba®)
•
Regular human insulin u-500 (Humulin R U-500 KwikPen®)
•
Insulin lispro U-200 (Humalog U-200 KwikPen®)
Cost Considerations
Insulin product
How supplied
Total units/pen
Cost
Cost/unit
Insulin glargine U-300
1.5 mL pens
450
$134
$0.30
Insulin glargine U-100
3 mL pens
300
$89
$0.30
Insulin glargine U-100
equivalent
3 mL pens
300
TBD
TBD
Insulin degludec U-200
3 mL pens
600
$213
$0.36
Insulin degludec U-100
3 mL pens
300
$107
$0.36
Regular human insulin
U-500 pen
3 mL pens
1,500
$320
$0.21
Regular human insulin
U-500 vial
20 mL vial
10,000
$1655
$0.16
Insulin lispro U-200
3 mL pens
600
$236
$0.39
Insulin lispro U-100
3 mL pens
300
$118
$0.39
Table adapted from: Mospan CM.JAAPA. 2016; 29(6):16-18;
Pricing from www.lexicomp.com as of October 2016
Drug Discount Programs
Insulin product
Insulin glargine U-300
Insulin degludec
U-200/U-100
Regular human insulin
U-500 pen
Insulin lispro U-200
Program Details
Discount cards are available
• Card can reduce copay to $15, with a maximal discount of $200/pack
• Can be used for the first 12 prescription fills
Sanofi Patient Connection Program
• May be able to decrease drug price to $0 copay
Discount cards are available
• Can decrease copayment to as low as $15 (maximal discount of $500 for each fill)
• Can be used for the first 24 prescription fills
Discount cards available
• Card can reduce copay to $25, with a maximum of 7 KwikPen packs per
prescription fills
• Can be used for the first 12 prescription fills
Discount cards available
• Can decrease copayment to as low as $25 (maximal discount of $100 for each fill)
• Can be used for the first 24 prescription fills
www.toujeo.com; www.tresiba.com; www.humulin.com; www.humalog.com;
Not Just an Outpatient Issue!
In the Inpatient Setting:
• Insulin pens are preferred by nurses
Felt it was easier to teach patients to self-administer insulin using a pen device
• Felt that the risk of a dosing error was lower with a pen device vs. syringe
•
• Reduced waste from using insulin pens instead of vials may
reduce cost
•
One study projected a cost savings of $36 per patient per hospital stay with
insulin pen use instead of insulin vials
Haines ST, et al. Am J Health-Syst Pharm. 2016; 73(suppl 5):S4-16.
A Risky Situation…
•
2009: At a Texas hospital in 2009, 2,114 insulin-dependent patients with
diabetes were exposed to disease transmission risk via used insulin pens
•
2011: Over 2,000 patients were exposed to used insulin pens at a Wisconsin
hospital and outpatient clinic
•
2013: Over 700 patients at a New York hospital may have been exposed
inadvertently to human immunodeficiency virus (HIV), hepatitis B, or
hepatitis C because of the reuse of insulin pens on multiple patients
http://www.ismp.org/newsletters/acutecare/showarticle.aspx?id=41
Discussion Question!
Are insulin pens used at your practice site?
If so, how do you decrease the risk of
reusing insulin pens?
Best Practices for Safe Use of Insulin Pen
Devices in Hospitals
• Recommendations have been made for each step in the medication-use
process
• Examples:
• “Warning! Confirm patient. Insulin pens are for use in one patient only”
• Require all health professionals to pass a competency assessment for
insulin pens (at the time of hire and periodically thereafter)
• Develop a system to prompt the proper disposal of insulin pens when
the order is discontinued
Haines ST, et al. Am J Health-Syst Pharm. 2016; 73(suppl 5):S4-16.
Key Takeaways
• 37% of patients treated for diabetes use insulin
• Many new insulin products are available, each with their own advantages
•
Cost may be a barrier to patient use, and drug discount programs are one
method of assisting patients reduce costs
• Addition of new insulin products can lead to further confusion with the various
devices available, which has implications for both the inpatient and outpatient
settings
CONCENTRATE!
KEY TAKEAWAYS OF NEW INSULIN
PRODUCTS
Sara Wettergreen, PharmD, BCACP
Assistant Professor of Pharmacotherapy
University of North Texas System College of Pharmacy