This a a 3 part assignment. First Part:
Prompt
Consider the public health challenge of your choosing from the perspective of a public/community health administrator.
Discuss the challenge.
Where appropriate, explain:
Approaches for assessing and controlling environmental hazards that affect community health.
Individual and community preparedness considerations regarding health emergencies and public disasters.
Advocacy for evidence-based social changes that improve the health of individuals and communities.
The Journal for Nurse Practitioners 16 (2020) 213e217
Contents lists available at ScienceDirect
The Journal for Nurse Practitioners
journal homepage: www.npjournal.org
Insulin Rationing
Leigh Hart, PhD, FNP-C
a b s t r a c t
Keywords:
analog insulin
diabetes mellitus
insulin cost
synthetic human insulin
The high cost of insulin in the United States has led to insulin rationing by some patients. This article presents
a case of insulin rationing and discusses evidence supporting the use of lower-cost synthetic human insulin in
some type 2 diabetics without a history of nocturnal hypoglycemia. Provider considerations for managing the
switch from analog insulin to synthetic human insulin are presented.
© 2019 Elsevier Inc. All rights reserved.
Jaye is a 34-year-old male patient with type 2 diabetes. A year
ago he passed out at home and was admitted to intensive care with
a blood sugar level of 1,200. Before this diagnosis, his medical
history was negative, except for a 100-lb weight gain when he
completed a rehabilitation program for substance use disorder 4
years earlier. He has been sober since that time. He was discharged
from the intensive care unit on 25 U detemir once a day, metformin
1,000 mg twice a day, and lisinopril 10 mg once a day. His primary
care nurse practitioner has titrated his insulin up to 40 U over the
last year, but he continues to have very high hemoglobin A1c levels.
He is employed and has health insurance through his employer.
He is the sole provider for his family. He has a wife and a 1-year-old
daughter, and he is expecting his second child in 6 months. He
works in an industrial setting and averages 60 hours of work a
week. Even with insurance and an income greater than $40,000 a
year, he is having difficulty paying the copay for his current basal
analog insulin. His nurse practitioner states he needs to add a rapidacting analog insulin at mealtimes because his last hemoglobin A1c
was 14%.
Jaye’s hemoglobin A1c is at this critical level because he has
been rationing his insulin because of cost. Recently, while on the
basal insulin alone, he had $100 to last 5 days until his next payday.
He was out of his basal analog insulin, but the $80 copay to refill his
prescription would not leave enough money for him to buy food for
the family and diapers for his 1-year-old daughter. He decided to
wait and go without his insulin until his next payday. By Thursday
of his second week without insulin, his blood sugar was so high that
his meter would not produce a reading and instead flashed “seek
medical attention.” He felt horrible but could not miss any work so
he “borrowed” 20 units of rapid-acting analog insulin from a
coworker, took the medication, and continued to drive his forklift.
Despite insurance and employment, this current plan of care is not
working for this patient. The addition of the bolus analog insulin
will help gain control of his hemoglobin A1c but not if he does not
https://doi.org/10.1016/j.nurpra.2019.10.023
1555-4155/© 2019 Elsevier Inc. All rights reserved.
take it. The new rapid-acting insulin will increase his monthly
copay to over $300. He cannot afford these medications. Is there a
safe, less expensive alternative for this patient?
The History of Insulin
A diagnosis of type 1 diabetes was fatal until the production of
the first commercial insulin in 1923.1 Dr. Frederick Banting
discovered the process for insulin extraction from bovine pancreas,
and Eli Lilly (Indianapolis, IN) was the first company to produce and
market this miracle drug.2 In 1926, crystallization of insulin
improved solubility, but the insulin was only available in a regular
formulation, and patients required multiple injections a day.2 In
1936, a fish protein called protamine and zinc were added to insulin, providing the first much-needed extended-action insulin
protamine zinc insulin.2 A reduction in the amount of protamine
led to neutral protamine Hagedorn (NPH) insulin in 1946. NPH
insulin has a shorter action time compared with protamine zinc
insulin and could be combined with regular insulin to more closely
mimic the basal/bolus pattern of insulin normally released by the
human body. This was followed by the Lente series, which altered
the amount of zinc and produced an intermediate-action insulin.2
Recombinant DNA technology led to a new human insulin
formulation marketed in 1983.2 Recombinant DNA technology uses
a common bacterium and inserts human genes into the genetic
material of the microorganism. The microorganism subsequently
produces the desired protein, in this case human insulin.
In 1996, the analog insulin lispro, a lysine-proline analog insulin,
was introduced as the fastest-acting insulin.3,4 This new rapid insulin has an onset of action of 5 to 15 minutes and a peak of 20
minutes to 90 minutes. This was followed by the basal insulins,
glargine in 2000 and detemir in 2005. Analog basal insulin lasts for
up to 24 hours and produces no or a very limited peak action time,
reducing the risk of hypoglycemia.2-4 These new basal analog
214
L. Hart / The Journal for Nurse Practitioners 16 (2020) 213e217
insulins can be used with rapid-acting analog insulins such as insulin aspart or insulin glulisine at mealtime to closely mimic the
natural patterns of insulin secretion.
Two analog biosimilar insulins are now available. In 2015,
Basaglar (Eli Lilly), a biosimilar form of the analog insulin glargine,
was Food and Drug Administration approved followed by Admelog
(Sanofi, Paris, France), the biosimilar formation of lispro in 2017.
Extensive cost savings have not yet been realized with the addition
of biosimilars. At the time of this writing, the GoodRx.com website
lists 3 insulin 3 mL U-100 pens for the brand insulin Lantus (SanofiAventis US; insulin glargine) for $215.20 with a coupon, whereas
the biosimilar Basaglar was $250.91.
Many ask why insulin is so expensive when it is not a new
product. The production of biosimilar medications is more costly
than other nonbiological medications. In addition, there are 3
manufactures that provide insulin in the United States. These
companies are Eli Lilly, Sanofi, and Novo Nordisk (Bagsvaerd,
Denmark). These companies also produce the 2 available biosimilar
formulations.
The analog insulins have become the most widely used insulins
in the United States.5 The JN Learning podcast titled “Health Care
Spending Gone Wild: Using Expensive Insulin Analogs With Few
Clinical Advantages” provides a good overview of the molecular
modifications used to produce the onsets and duration of action for
analog insulins.5
investigated by a bipartisan Senate Finance Committee with a goal
to stabilize and lower the cost of insulin.8 As our case study illustrates, even with insurance, the copay for insulin analogs may be
too high for some patients. Table 1 presents a summary of certain
insulin types and their costs currently available in the US according
to GoodRx.com.
Lipska9 concludes that recent studies provide evidence that the
expensive insulin analogs do not offer substantial benefits for some
type 2 diabetics.9 The less expensive synthetic human insulins may
lower the financial burden for certain individuals with type 2 diabetes while maintaining good patient outcomes. Lipska et al10
identify candidates for this change as people with type 2 diabetes
without a history of severe nocturnal hypoglycemia. Switching a
patient with type 2 diabetes on an analog basal bolus regimen to a
premixed human 70/30 insulin could result in significant cost
savings and reduce the risk for insulin rationing. In some patients, it
may also lower daily injection burden.10
Human insulin may be an option for some patients with type 1
diabetes who are unable to afford analog insulin. However, there
are identified advantages for patients with type 1 diabetes to be
placed on analog insulins.10 The focus of this article is on insulin
options for patients with type 2 diabetes who do not have a history
of severe nocturnal hypoglycemia.
The High Cost of Insulin
Lipska et al11 completed a retrospective study of Kaiser Permanente of Northern California, Oakland, CA, clients.11 Although insulin analogs are used by more patients with diabetes than other
forms of insulin, Kaiser Permanente of Northern California preferentially uses human insulin. This retrospective study compared the
outcomes of patients with type 2 diabetes mellitus initiated on
basal analog insulin (n ¼ 25,489) and patients initiated on NPH
human insulin (n ¼ 23,561). This study did not find significant
differences in emergency department visits or hospital admissions
The price for insulin analogs has increased dramatically in
recent years. “Insulin prices tripled from 2002 to 2013 and then
nearly doubled 2012 to 2016” for almost the exact same product.6
Similar to the case study presented earlier, there are increasing
reports in the media about people with diabetes rationing their
insulin to the point of severe illness and even death.7 The crisis has
captured the attention of US Congress and is currently being
Review of Evidence
Table 1
Comparison of Insulin Prices for Commonly Used Insulins
Generic Name
Trade Name
Type
Cost per Unit
Rapid
Insulin aspart
Novolog® (Novo Nordisk)
Analog
Insulin glulisine
Apidra® (Sanofi-Aventis)
Analog
Insulin lispro U 100
Humalog® U100 (Lilly)
Analog
$294.86 (U-100/10-mL vial)
$561.65 (5 pens u100/3ml)
$271.93 (U-100/10-mL vial)
$512.40 (5 pens U-100/3 mL)
$122.87 (U-100/10-mL vial)a
$230.27 (5 pens U-100/3 mL)a
$224.77 (3 pens U-200/3 mL)
$137. 85 (U-100/10-mL vial)
Insulin lispro U 200
Insulin lispro
Regular
Regular insulin U100
Regular insulin U 500
®
Humalog U 200 (Lilly)
Admelog® (Sanofi-Aventis)
Analog
Biosimilar Analog
Humulin R® U100 (Lilly)
Humulin R® U 500 (Lilly)
Human
Human
$24.88 (vial)
$1,561 U-500 20-mL vial
Not for ordinary use
Humulin N® (Lilly),
Novolin N® (Novo Nordisk)
Human
$96.25 (U-100/10-mL vial)
$24.88 (U-100/10-mL vial)
Long Acting
Insulin detemir
Levemir® (Novo Nordisk)
Analog
Insulin glargine
Lantus® (Sanofi-Aventis)
Analog
Biosimilar analog
$313.46 (U-100/10-mL vial)
$465.99 (5 pens U-100/3 mL)
$213.44 (U-100/10-mL vial)
$215.20 (3 pens U-100/3 mL)
$250.91 (3 pens U-100/3 mL)
Analog
Analog
Analog
$324.04 (3 pens U-100/3 mL)
$511.75 (3 pens U-100/3 mL)
$612.41 (3 pens U-200/3 mL)
Intermediate
NPH insulin
Insulin glargine
Ultraelong Acting
Insulin glargine U 300
Insulin degludec U 100
Insulin degludec U 200
®
Basaglar (Lilly)
®
Toujeo (Sanofi-Aventis)
Tresiba® (Novo Nordisk)
Tresiba® (Novo Nordisk)
Prices listed are the lowest posted total cost from GoodRx (https://www.pharmacist.com/practice-insights-emerging-insulins and https://www.goodrx.com/admelog)
without insurance at the time of this writing.
a
Retail prices listed at $170 per vial and $322 per 5-pen set.
L. Hart / The Journal for Nurse Practitioners 16 (2020) 213e217
for hypoglycemic events between the 2 groups. It is interesting to
note that the average hemoglobin A1c level in both groups of patients was above the recommended value of 7%, with the basal
analog cohort reaching a mean hemoglobin A1c of 8.2% (95% confidence interval [CI], 8.1%-8.2%) in 1 year and the NPH cohort
reaching a mean hemoglobin A1c of 7.9% (95% CI, 7.9%-8.0%).11
Luo et al12 evaluated a health plan program designed to lower
patient and company cost by switching people with type 2 diabetes
from very high-cost analog insulin to lower-cost human insulins.
This was a retrospective cohort study of 4,635 participants.12 Participants were given financial incentives to self-select human insulin regimens over the more expensive analogs. The switch was
available across the health care plan, but the ideal candidate was an
adult with type 2 diabetes on more than 2 injections a day, not
prone to hypoglycemia, on more than 50 U a day, and/or a history of
nonadherence. A dose conversion protocol was used to convert
patients who selected to change from analog to human insulin. All
analog insulins and secretagogues were stopped. The new premixed human 70/30 insulin or NPH insulin dosage was calculated
at 80% of their former total daily dose (TDD) of analog insulin. For
the participants switching to a premixed human 70/30 insulin, two
thirds of the TDD was taken before breakfast, and one third of the
TDD was taken before dinner. For some patients, this lowered the
daily injection burden. Outcome measures were compared 12
months before and 12 months after the switch. A slight increase in
hemoglobin A1c of 0.14 % (95% CI ,0.05%-0.23%) was found to be
statistically significant (P ¼ .003) but not clinically significant. These
authors conclude that to be clinically significant the change in
hemoglobin A1c would be 0.5% or greater. There was not a significant change in serious hypoglycemic events between the 2 groups
(P ¼ .61 for both groups).
Nabrdalik et al13 completed an observational study (N ¼ 3,264)
comparing patients on premixed human and analog insulin in
relationship to efficacy, safety, and satisfaction. This study found
that both groups had a reduction in hemoglobin A1c levels, but the
hemoglobin A1c levels were significantly higher (P < .001) in the
215
human insulin group compared with the analog group (7.72% vs
7.57%). Nabrdalik et al found no difference between the groups in
hypoglycemic events. This study also evaluated patient satisfaction
using the Diabetes Treatment Satisfaction Questionnaire. Both
groups were satisfied with their treatment regimen, with higher
reports of patient satisfaction in the human insulin group. The
authors did not elaborate or discuss what may have contributed to
this increase in satisfaction.13
These studies provide evidence that synthetic human insulin
may be an alternative for certain patients with type 2 diabetes who
do not have a history of severe hypoglycemia.11-13 Hypoglycemia
has been associated with macro- and microvascular disease and
death from vascular and nonvascular causes.14 Patients identified as
having an increased risk for hypoglycemia include “older age,
longer duration of diabetes, higher creatinine levels, lower body
mass index, lower cognitive function, use of two or more oral
glucose-lowering drugs, history of smoking or microvascular disease, and assignment to intensive glucose control.”14 Insulin analogs are associated with a lower risk for hypoglycemia and are the
recommendation to prevent hypoglycemia.15
Switching From Analog to Human Insulin
One concern noted in the podcast “Health Care Spending Gone
Wild: Using Expensive Insulin Analogs With Few Clinical Advantages” is that newer providers may not be familiar with prescribing
the older human formulation of insulin because of the fact that
currently 90% of diabetics on insulin are using the newer analog
versions.5 The differences in action between the analogs and human insulin require close provider monitoring if it is decided to
switch analogs to synthetic human insulin. Table 2 provides an
overview of insulin type, dosing, and action profile and table.10
Lipska et al10 note that when switching patents from analog to
human insulin, they should consider that patients may not have
been taking their full prescribed dose of analog insulin. They
recommend beginning the switch by reducing the current daily
Table 2
Insulin Type, Dosing, and Action Profile10,16
Synthetic Human Insulin
Type
Onset
Peak
Duration
Dosing Frequency
NPH (Humulin N®a) (Novolin N®)
Regular (Humulin R®a) (Novolin R®)
Insulin NPH 70%/insulin regular 30% (Humulin® 70/30a)
(Novolin® 70/30)
2-4 h
30-60 min
30-60 min
4-10 h
2-3 h
2-6 h
12-18 h
8-10 h
12-18 h
HS, BID
0-30 minutes before meals
BID
Before breakfast and dinner
Insulin Analogs
Type
Basal Insulins
Degludec U-100 and U-200 (Tresiba®)
Detemir U-100 (Levemir®)
Glargine U-100 (Lantus®)
Glargine U-300 (Toujeo®)
Biosimular Glargine U-100 (Basaglar®)Rapid-acting Insulin
Aspart U-100 (Novolog®)
Glulisine U-100 (Apidra®)
Lispro U-100 Pen U-200 (Humalog®)
Premixed insulin aspart protamine 70% and insulin aspart
30% (Novolog® 70/30)
75% insulin lispro protamine 75% and insulin lispro
25% (Humalog® 75/25)
75% insulin lispro protamine 50% and insulin lispro
50% (Humalog® 50/50)
Onset
Peak
Duration
Dosing Frequency
1h
3-4 h
2-6 h
None identified
3-9 h
None identified
> 40 h
6-24 h
20-24 h
QD
QD, BID (for higher doses)
QD, BID (for higher doses)
5-15 min
5-15 min
5-15 min
5-15 min
30-90 min
30-90 min
30-90 min
2-4 h
2-6 h
2-6 h
2-6 h
14-24
0-15 min before meals
0-15 min before meals
0-15 min before meals
Before breakfast and dinner
BID ¼ twice a day; HS ¼ hour of sleep; QD ¼ every day.
a
At the time of this writing, Novolin was approximately one third the cost of Humulin.
216
L. Hart / The Journal for Nurse Practitioners 16 (2020) 213e217
Table 3
Considerations for Using Human Insulin Instead of Analogs10
Concern
Consider
Injection techniques
Regular human insulin is recommended to be injected 30 minutes before a meal as opposed
to with the meal for rapid-acting analogs.
The least expensive human insulin does not come in a pen.
Patients must have the physical and cognitive ability to accurately draw up and administer this insulin.
100 insulin syringes can be purchased for $24.00 at the time of this writing.
Human N must be gently agitated to mix the suspension.
May start at 10 U in the evening and titrate up by 2 units once or twice a week until target FBS and A1c is achieved.
May titrate to 2 injections per day 1 at breakfast and 1 in the evening.
Meal time R may be started at 6 U.
Two injections: 1/2 daily dose before breakfast and 1/2 daily dose with dinner.
If the A1c is greater than 9%, the start can be 0.3 U/kg/d for the total daily dose.
Monitor for midday and midnight hypoglycemia.
Reduce total daily dose on analogs by 20% when switching from analog to human insulin. For example,
if the total daily dose on analogs is 50 U, start human insulin at 40 U.
Premixed human insulins may allow for a reduction in total daily injection burden for people on a basal
bolus analog pattern.
The nocturnal hypoglycemia risk should be a consideration in the switch from analog to
human insulin. Analog insulins may provide benefits to those with a history of nocturnal hypoglycemia.
Consider in-office or telephone monitoring during the switch to monitor for hypoglycemia events.
Patient education
More frequent home glucose monitoring during dosage changes, illness, or change in dietary or activity patterns
Consider less aggressive hemoglobin A1c targets when appropriate.
Consider glucose monitoring before bed and a bedtime snack regimen.
Pen or vial
Human N and R
Premixed
NPH 70/regular 30
Switching from analog to human
Nocturnal hypoglycemia
N ¼ NPH; NPH ¼ neutral protamine Hagedorn; R ¼ regular.
dose of insulin by 20%.10 Human insulins do not provide 24-hour
coverage like the basal analogs. Because of this, 2 injections a day
will be required.10 Table 2 presents an overview of the onset, peak,
and duration for synthetic human and analog insulin. Table 3 presents a summary of provider considerations when prescribing
switching a patient from analogs to synthetic human insulin.5
In the case presented at the beginning of this article, a decision
was made to transition Jaye to a premixed human NPH 70%/regular
30% insulin. He is an ideal candidate because of his lack of nocturnal
hypoglycemic episodes, his financial circumstances, and the daily
injection burden a change to an analog basal bolus regimen would
present. His analog TDD of insulin was reduced from 40 U of a basal
analog to 32 of premixed human NPH 70/regular 30 insulin.
Initially, 20 U will be given before breakfast and 12 U with the
evening meal. The dosage will be titrated up by 2 U every 3 to 4
days until the target fasting glucose and A1c levels are obtained.
Jaye was kept on the metformin and lisinopril. Extensive insulin
education was provided to Jaye, including the frequency of glucose
monitoring and how to recognize and prevent hypoglycemia. The
risk for midday and nocturnal hypoglycemia was emphasized. Jaye
was instructed not to skip meals, and while transitioning to the
new insulin regimen, he checks his glucose before bed and eats a
snack from a preapproved list if his glucose is less than 140. Jaye
will report to the office by phone for the next few days and come in
for a follow-up appointment in 1 week.
Conclusion
The cost burden for insulin is an urgent health care concern in
the US. Although insulin analogs have been considered the
preferred insulin in the US, the high cost and copays for this
product may lead to insulin rationing and poor patient outcomes.
Lower-cost synthetic human insulin may be a good alternative for
certain people with type 2 diabetes without a history of severe
nocturnal hypoglycemia.
There are options for patients who are not candidates for the
lower-cost human insulin alternatives. All 3 of the major insulin
manufactures, Sanofi, Eli Lilly, and Novo Nordisk, have patient
assistance programs advertised on their websites. These programs
provide coupons and discounts for insulin for patients who meet
certain criteria. GoodRx.com is another source for coupons for drug
discounts.
There are efforts underway to lower the cost of insulin in the US.
In addition to the Senate hearings on the high cost of drugs in the
US, some states such as Florida are considering importing drugs
from Canada.8 Until the efforts are successful, it is important to
work with people with diabetes to find the insulin regimen that
works best for them from both a financial and health outcomes
measure. You can join in efforts to promote insulin accessibility and
affordability
by
signing
the
petitions
at
https://
makeinsulinaffordable.org/.
References
1. American Diabetes Association. Science, hope, progress. https://www.diabetes.
org/resources/timeline. Accessed July 31, 2019.
2. White JR. A brief history of the development of diabetes medications. Diabetes
Spectr. 2014;27(2):82-86.
3. Tibaldi JM. Evolution of insulin: from human to analog. Am J Med.
2014;127(10):S25-S38.
4. Quianzon CC, Cheikh I. History of insulin. J Community Hosp Intern Med Perspect. 2012;2(2). https://doi.org/10.3402/jchimp.v2i2.18701.
5. American Medical Association. JN Learning. Health care spending gone wild:
using expensive insulin analogs with few clinical advantages .
May 16, 2019. https://edhub.ama-assn.org/jn-learning. Accessed July 31, 2019.
6. Weixel N. Drug pricing fight centers on insulin. The Hill. 2019. https://
thehill.com/policy/healthcare/430680-drug-pricing-fight-centers-on-insulin.
Accessed July 31, 2019.
7. Smith-Sabel B. Insulin’s high cost leads to lethal rationing. Shots health
news from NPR. 2018. https://ju.idm.oclc.org/login?url¼https://search.
ebscohost.com/login.aspx?direct¼true&db¼ccm&AN¼103945600&site¼ehostlive. Accessed July 31, 2019.
8. Barrett J. Rising insulin costs addressed at Senate hearing on drug prices.
Pharmacy Times. 2019. https://www.pharmacytimes.com/resource-centers/
diabetes/rising-insulin-costs-addressed-at-senate-hearing-on-drug-prices.
Accessed July 31, 2019.
9. Lipska KJ. Insulin analogues for type 2 diabetes. JAMA. 2019;321(4):350-351.
https://doi.org/10.1001/jama.2018.21356.
10. Lipska KJ, Hirsch IB, Riddle MC. Human insulin for type 2 diabetes: an effective,
less-expensive option. JAMA. 2017;318(1):23-24. https://doi.org/10.1001/
jama.2017.6939.
11. Lipska KJ, Parker MM, Moffet HH, Huang ES, Karter AJ. Association of initiation
of basal insulin analogs vs neutral protamine Hagedorn insulin with
hypoglycemia-related emergency department visits or hospital admissions
and with glycemic control in patients with type 2 diabetes. JAMA. 2018;320(1):
53-62. https://doi.org/10.1001/jama.2018.7993.
L. Hart / The Journal for Nurse Practitioners 16 (2020) 213e217
12. Luo J, Khan NF, Manetti T, et al. Implementation of a health plan program for
switching from analogue to human insulin and glycemic control among
Medicare beneficiaries with type 2 diabetes. JAMA. 2019;321(4):374-384.
https://doi.org/10.1001/jama.2018.21364.
13. Nabrdalik K, Kwiendacz H, Sawczyn T, et al. Efficacy, safety, and quality of
treatment satisfaction of premixed human and analogue insulin regimens in a
large cohort of type 2 diabetic patients: PROGENS BENEFIT observational study.
Int J Endocrinol. 2018;1(suppl):1-7. https://doi.org/10.1155/2018/653617.
14. Zoungas S, Patel A, Chalmers J, et al, ADVANCE Collaborative Group. Severe
hypoglycemia and risks of vascular events and death. N Engl J Med.
2010;363(15):1410-1418.
217
15. Howard-Thompson A, Khan M, Jones M, George CM. Type 2 diabetes mellitus:
outpatient insulin management. Am Fam Physician. 2018;97(1):29-37.
16. Woo TM, Robinson MV. Pharmacotherapeutics for Advanced Practice Nurse
Prescribers. 4th ed. Philadelphia, PA: FA Davis; 2016.
Leigh Hart, PhD, FNP-BC, is a professor at Jacksonville University in Jacksonville, FL, and
can be contacted at lhart@ju.edu.
In compliance with national ethical guidelines, the author reports no relationships
with business or industry that would pose a conflict of interest.
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