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DOI:10.4158/EP-2018-0223
© 2018 AACE.

Original Article EP-2018-0223

GLUCAGON PRESCRIPTIONS FOR DIABETES PATIENTS AFTER EMERGENCY DEPARTMENT

VISITS FOR HYPOGLYCEMIA

A. Mark Fendrick, MD2, Xuanyao He, PhD1, Dongju Liu, MS1, Jason D. Buxbaum, MHSA2,
Beth D. Mitchell, MPH, BSN, RN1

Running Title: Glucagon prescriptions after an ED visit for hypoglycemia

From: 1Eli Lilly and Company, Indianapolis, IN 46285; 2 Center for Value-Based Insurance
Design, Ann Arbor, MI 48105

Corresponding Author: Beth D. Mitchell

Lilly Corporate Center
Indianapolis, IN 46160
Email: Mitchell_Beth_D@lilly.com

DOI:10.4158/EP-2018-0223
© 2018 AACE.
Abstract

Objective To determine the proportion of prescription fills for glucagon within 90 days of an

emergency department (ED) visit for hypoglycemia.

Methods This is a retrospective research study of glucagon prescriptions filled after an ED visit

for hypoglycemia (from January 2011 to June 2014) by people with Type 1 diabetes (T1D) and

people with Type 2 diabetes (T2D) taking insulin who did not already have an unexpired

glucagon prescription within the Truven Health MarketScan® Research Database.

Results Less than 10% (T1D: 10.9%; T2D: 3.5%) filled a glucagon prescription after the ED

visit.

Conclusion A substantial opportunity exists to improve care for at-risk patients with diabetes

through a more consistent provision of glucagon, perhaps through the implementation of a

quality metric.

Keywords: hypoglycemia, glucagon, emergency department, quality measures

Acknowledgments

The authors acknowledge Rod Everhart (Syneos Health) for his critical review of the manuscript

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Abbreviations:

ED = Emergency Department; T1D = Type 1 diabetes; T2D = Type 2 diabetes; US = United

States; DM = diabetes mellitus; ICD-9-CM = International Classification of Diseases, Ninth

Revision, Clinical Modification; CCI = Charlson Comorbidity Index; SD = standard

deviation; IQR = interquartile range; Rx = prescription.

INTRODUCTION

Severe insulin-related hypoglycemia is associated with seizures, cardiac events, and fatalities and

is often iatrogenic in nature (1). Insulin related hypoglycemia accounts for nearly 100,000

emergency department (ED) visits annually in the United States (US), about 30 percent of which

result in inpatient admissions (2). Inpatient admissions for hypoglycemia now exceed admissions

for hyperglycemia for Medicare fee-for-service beneficiaries aged 65 and older (3).

American Diabetes Association guidelines state that glucagon should be prescribed to all patients

with diabetes mellitus (DM) at increased risk of clinically significant hypoglycemia (4).

However, a limited literature search suggests that DM patients at risk for hypoglycemia often

have expired glucagon at home or do not know if the glucagon used in the case of a severe

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hypoglycemic event is expired (5,6). A history of a prior hypoglycemic episode requiring acute

care and insulin use increases the risk of severe hypoglycemia (7,8); one study estimated that a

prior history of severe hypoglycemia raises the risk of future severe hypoglycemia events by a

factor of 4 (7).

No population-based study has assessed glucagon prescriptions among people at risk for severe

hypoglycemia, such as those people with diabetes taking insulin who have experienced an ED

visit associated with hypoglycemia. The purpose of this research was to quantify the rate at

which people at risk for severe hypoglycemia had possession of glucagon as per medical care

guidance. Accordingly, to quantify glucagon receipt, we analyzed insurance claims from a cohort

of insulin users who had an ED visit for hypoglycemia and who did not already have an

unexpired glucagon prescription.

METHODS
Data Source and Study Population

The Truven Health MarketScan® Research Databases contain individual-level, de-identified,

healthcare claims information from employers, health plans, hospitals, and Medicare and

Medicaid programs. Since their creation in the early 1990s, the MarketScan Databases have

grown into one of the largest collections of de-identified patient-level data in the US. These

databases reflect real-world treatment patterns and costs by tracking millions of patients as they

travel through the healthcare system, offering detailed information about all aspects of care. Data

about individual patients are integrated from all providers of care, maintaining healthcare

utilization and cost-record connections at the patient level. Used primarily for research, these

databases are fully compliant with US privacy laws and regulations (i.e., HIPAA). Research

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using MarketScan data has been widely published in peer-reviewed medical and health services

journals. (9). No ethical approval was required.

The study sample included people with diabetes who had at least one ED visit for hypoglycemia

(index event) between January 1, 2011 and June 30, 2014 (N=251,809). The hypoglycemia event

had to have the same date as the ED visit. Since the shelf life of glucagon is 2 years, people who

had filled a glucagon prescription in the 2 years before the index ED event were excluded to be

confident that a new glucagon prescription was needed (excluded only 3.3% of the original

sample). Further, people needed to be continuously enrolled for 3 years (2 years before and at

least 1 year after the index event) (N=86,182). The sample was then limited to people taking

insulin; only those who had filled at least two prescriptions of any insulin in each of these

continuous years were included (N=19,778). To analyze by diabetes type, only those meeting the

definition for Type 1 diabetes (T1D) or Type 2 diabetes (T2D) were included, which resulted in

5.5% of the original sample or N=13,744. Finally, the main outcome measure could be

influenced by insulin regimen, so each regimen was defined as having filled at least 2

prescriptions in a year of either basal only, basal and bolus, and insulin mixtures only (Table 1).

Cohort Definition

The overall population refers to individuals who had at least one ED visit for hypoglycemia. The

index event was identified as the first ED visit for hypoglycemia that happened between January

1, 2011 and June 30, 2014. A validated algorithm was used to identify hypoglycemia visits in

administrative data sets (10). The cohort was divided by T1D and T2D from an adapted

algorithm based upon International Classification of Diseases, Ninth Revision, Clinical

Modification (ICD-9-CM) codes (11).

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 Identification of Key Events, Comorbidities, and Demographics

The main outcome measure was the proportion of people who filled a glucagon prescription

within 90 days after the index ED event. Secondary analyses included the timing of filling a

glucagon prescription relative to the index ED visit (within 90 days and within 1 year post-

index). Exploratory analyses were undertaken to examine 30-day ED readmissions for

hypoglycemia to study a potentially important quality metric to hospitals (12). Patient

demographics were characterized at index ED date, and comorbidities were classified at the pre-

index period. To classify comorbidities of interest, ICD-9-CM codes were used to identify acute

coronary syndrome, heart failure, peripheral vascular disease, renal disease, neuropathy,

retinopathy, ketoacidosis, cerebrovascular disease, myocardial infarction, and cardiovascular

disease. The Charlson Comorbidity Index (CCI), a tool for categorizing comorbidities and

predicting mortality or higher resource use, was averaged (13). A higher CCI score means higher

disease severity.

Analytic Plan

Descriptive statistics were generated and included patient demographics, insulin treatment type,

baseline comorbidities, and 2-year history of ED-related hypoglycemia. The number and

percentage of people who filled a glucagon prescription within 90 days, and within 1 year after

the index event, for T1D and T2D separately, were quantified. Meanwhile, the baseline

characteristics (e.g., age, gender, insulin type, history of ED-related hypoglycemia,

comorbidities, etc.) of those who filled a glucagon prescription within 90 days after index date

and those who did not were described, i.e., numbers and percentages of people were reported for

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categorical variables, and the mean and standard deviation (SD) were reported for continuous

variables. The Student’s t-test for continuous variables and chi-square test for categorical

variables were used for comparison between the two groups. For the time from index event to

glucagon prescription, the median and interquartile range (IQR) was reported.

All the above analyses were conducted using SAS version 9.2 (SAS Institute Inc., Cary, NC).

RESULTS

There were 3,177 people with T1D and 10,567 people with T2D who had an ED visit for

hypoglycemia and met the additional study inclusion and exclusion criteria. Of those individuals

with T1D, 10.9% (n=346), and 3.5% (n=372) with T2D filled a glucagon prescription within 90

days of the index ED visit for hypoglycemia (Table 2). Of those who filled glucagon within 90

days, median time to fill was 15 (IQR: 4-43) days and 9 (IQR: 3-36) days, for T1D and T2D,

respectively (Figure 1).

There were 291 (9.2%) people with T1D and 1,184 (11.2%) people with T2D who had a 30-day

ED readmission for hypoglycemia.

The baseline characteristics between people who filled and who did not fill a glucagon

prescription within 90 days are shown in an online appendix. Overall, the percentage of people

filling basal-bolus insulin prescriptions or on commercial insurance was significantly higher with

those who did fill versus those who did not fill glucagon. The percentage of people with T1D

≤18 years and with T2D ≥65 years is higher among those who filled glucagon when compared

with those who did not.

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DISCUSSION

Guidelines call for DM patients at increased risk of clinically significant hypoglycemia to have

prescription glucagon available for rescue if needed (4). This retrospective, population-based

study found that only 5% of insulin users who had recently presented to the ED with

hypoglycemia, established risk factors for future instances of severe hypoglycemia (7,8), filled a

prescription for glucagon within 90 days after the ED visit. Since patients with T2D experienced

more hypoglycemia ED events and were less likely to fill a glucagon prescription, quality

improvement efforts should focus on all insulin users who experience a severe hypoglycemia

event.

These disappointing findings are consistent with the body of literature suggesting substantial

opportunity to improve care for patients with diabetes at risk of severe hypoglycemia (14).

Improvements that prevent even a fraction of the 100,000 annual ED visits for insulin-related

hypoglycemia (2) could avert substantial clinical morbidity and produce considerable cost

savings.

Improved measurement of quality of care for patients at risk of hypoglycemia is critical. A 2017

study reported that of 23 performance measure initiatives since 2011, 21 did not include

performance measures corresponding to hypoglycemia (15). Suitable measures should be

developed and adopted.

Both provider-facing and patient-engagement interventions can be implemented to reduce the

incidence of these preventable episodes. Such efforts might include the use of clinical support

services such as “best practice alerts” and/or diagnosis-based checklists to identify patients not in

possession of glucagon at the time of ED diagnosis. As has been described elsewhere,

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partnerships with in-facility pharmacies could be implemented to provide education and

glucagon for patients at discharge.(14) The patient’s role in reducing recurrent hypoglycemia

events could be enhanced and supported if education/training for patients, family members, and

caretakers was to be delivered on site (5,6) and consumer cost-sharing for glucagon was reduced

or eliminated for high-risk DM patients (i.e., use of value-based insurance design) (16). These

interventions could increase the likelihood that a prescription be filled.

Limitations of insurance claims research are well documented (e.g., coding errors, incomplete

data). However, in identifying the index event, the Gold Standard, Ginde Method was used in

this research and has been validated for use in identifying hypoglycemia visits. Another

limitation is that this research does not allow an assessment of prescriptions ordered, only

prescriptions filled.

CONCLUSIONS

Severe hypoglycemia is associated with an enormous clinical and financial burden, some of

which could be prevented with the increased use of guideline-recommended services (17-19). A

substantial opportunity exists to improve care for patients who have already experienced a

hypoglycemic event necessitating an ED visit through the more consistent provision of glucagon,

perhaps through the implementation of a quality metric. Both provider and patient-focused

efforts are needed to improve outcomes and lower medical costs for this at-risk population.

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REFERENCES.

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10. Ginde AA, Blanc PG, Lieberman RM, Camargo CA Jr. Validation of ICD-9-CM coding

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hospital discharge: a missing part of the equation. Ann Emerg Med. 2013 Apr 4 [Epub ahead

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CM administrative databases. J Clin Epidemiol. 1992;45:613-619.

14. Ginde AA, Pallin DJ, Camargo CA Jr. Hospitalization and discharge education of emergency

department patients with hypoglycemia. Diabetes Educ. 2008;34:683-691.

15. Rodriguez-Gutierrez R, Ospina NS, McCoy RG, et al, for the Hypoglycemia as a Quality

Measure in Diabetes Study Group. Inclusion of hypoglycemia in clinical practice guidelines

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2016;176:1714-1716.

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18. Boulin M, Diaby V, Tannenbaum C. Preventing unnecessary costs of drug-induced

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Figure Legend

Fig. 1. (a) Time to glucagon prescription in 1 year, Type 1 diabetes. (b) Time to glucagon
prescription in 1 year, Type 2 diabetes.

Abbreviation: Rx=prescription

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Table 1. Attrition table for study population

Criteria N %

Patients who had at least one emergency department (ED)

visit for hypoglycemia from 01/01/2011 to 06/30/2014 in
Commercial, Medicare, or Medicaid database 251,809 100

Patients had no glucagon 2 years before ED visit for

hypoglycemia (index date = first ED visit for
hypoglycemia) 243,574 96.7

Patients have continuous enrollment for 24 months pre- and

12 months post-index date 86,182 34.2

Patients received ≥2 prescriptions of any insulin each year

for 3 continuous years 19,778 7.9

Patients meet T1D/T2D definition 13,744 5.5

T1D patients 3177 1.3

T1D basal-bolus insulin users 902 0.4

T1D basal insulin only users 67 0

T1D insulin mixture users 136 0.1

T2D patients 10,567 4.2

T2D basal-bolus insulin users 2233 0.9

T2D basal insulin only users 1400 0.6

T2D insulin mixture users 1056 0.4

Abbreviations: T1D=type 1 diabetes; T2D=type 2 diabetes

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 Table 2. Number and Proportion of People Filling a

Glucagon Prescription Within 90 Days Post-Index Event

Diabetes Type n (%)

T1D (N=3,177) 346 (10.9%)

Any insulin
T2D (N=10,567) 372 (3.5%)

T1D (N=902) 104 (11.5%)

Basal-bolus insulin
T2D (N=2,233) 98 (4.4%)

T1D (N=67) 2 (3.0%)

Basal insulin only
T2D (N=1,400) 18 (1.3%)

T1D (N=136) 6 (4.4%)

Insulin mixtures
T2D (N=1,056) 18 (1.7%)

Abbreviations: T1D=Type 1 diabetes; T2D=Type 2 diabetes

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Fig. 1a. Time (days) to first glucagon prescription filled after the index date/event
Type 1 Diabetes

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Fig. 1b. Time (days) to first glucagon prescription filled after the index date/event
Type 2 Diabetes

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