Case Report
ROLE OF STEROIDS IN REFRACTORY HYPOGLYCEMIA
DUE TO AN OVERDOSE OF 10,000 UNITS OF INSULIN GLARGINE:
A CASE REPORT AND LITERATURE REVIEW
Komal Tariq, MD1; Saira Tariq, MBBS2; Amanda M. Denney Queen, MD1
ABSTRACT
Objective: A massive overdose of insulin glargine is
an emergent condition that causes prolonged and refractory
hypoglycemia, which may lead to coma and even death.
We present a case of an intentional overdose with the
highest reported dose of 10,000 units of insulin glargine
(Lantus®, 100 units/mL). In addition to the use of glucagon
and octreotide, we report here the benefit of adding steroids
to the regimen.
Methods: The case report is accompanied by a review
of the literature.
Results: A 36-year-old female presented nearly 44
hours after a massive overdose of 10,000 units of insulin
glargine. The patient was admitted to the intensive care unit
and required continuous dextrose infusion for 150 hours
along with frequent dextrose 50% boluses. Pharmacological
therapies used included glucagon to promote glycogenoly-
sis and gluconeogenesis, octreotide to prevent any endog-
enous insulin secretion from the pancreas, and steroids
for their hyperglycemic effects. Although not much effect
was noted on blood glucose levels with the glucagon and
octreotide, steroids did bring down the dextrose require-
ments after they were initiated. The patient was transferred
out of intensive care on day 6 for the psychiatric unit.
Submitted for publication January 30, 2017
Accepted for publication June 4, 2017
From 1The Christ Hospital Health Network, Cincinnati, Ohio, and
2Foundation University Medical College, Islamabad, Pakistan.
Address correspondence to Dr. Komal Tariq, The Christ Hospital, Internal
Medicine Residency, 2139 Auburn Avenue, Cincinnati, OH 45219.
E-mail: komaltariq@yahoo.com.
DOI: 10.4158/EP171780.CR
To purchase reprints of this article, please visit: www.aace.com/reprints.
Copyright © 2018 AACE.
e70 AACE CLINICAL CASE REPORTS Vol 4 No. 1 January/February 2018
This is an Open Access article under the CC-BY-NC-ND license.
Conclusion: Physicians should keep in mind that a
massive overdose with insulin glargine can be life threaten-
ing because the hypoglycemia can be severe and prolonged
therefore it requires prompt intensive care unit admission,
frequent glucose checks and sustained dextrose infusion
along with close electrolyte monitoring. While there is
no prior case report of steroid use for insulin overdose,
they proved to be beneficial in the current case. (AACE
Clinical Case Rep. 2018;4:e70-e74)
Abbreviation:
D50 = dextrose 50%
INTRODUCTION
Insulin glargine is a long-acting, recombinant human
insulin analogue administered once daily to maintain a
constant basal insulin level. Human insulin consists of
A and B chains, and insulin glargine is similar but has 2
arginine residues added to the B chain and asparagine is
replaced by glycine at position 21 of the A chain. These
substitutions help with stabilization of the molecule, lead-
ing to duration of action around 24 hours. However, case
reports have shown that overdoses may have hypoglyce-
mic effects for as long as 5 days (1-15). The proposed theo-
ries for this prolonged duration of action include the micro-
precipitation of insulin glargine in the subcutaneous tissue
leading to a ‘depot’ effect (1), down regulation of insulin
receptors in target tissues (1), and the latest research show-
ing the formation of an active metabolite, glargine-M1, at
the injection site (2).
The PubMed database was used to search for case
reports of insulin glargine overdose and less than 20 were
found, with the highest overdose level being 4,800 units
(3). In another incidence, 3,600 units were reported with
hypoglycemia lasting 120 hours (4).
Copyright © 2018 AACE
Copyright © 2018 AACE Steroids in Insulin Overdose, AACE Clinical Case Rep. 2018;4(No. 1) e71
CASE REPORT
A 36-year-old female with a history of bipolar disor-
der, obsessive-compulsive disorder, type 2 diabetes melli-
tus, chronic kidney disease stage 3, hypothyroidism, obesi-
ty (body mass index 47 kg/m2), and multiple prior suicide
attempts was transferred to our intensive care unit from an
outside facility, where she presented nearly 44 hours after
a massive overdose of 10,000 units of insulin glargine
(Lantus®, 100 units/mL). The patient lived alone and had
stored vials of prescribed insulin glargine. She was previ-
ously taking 200 units nightly but no longer required it for
blood glucose control since an intentional weight loss of
100 pounds and hemoglobin A1c of 5.2% over the previous
6 months. Two weeks prior to overdose, her hemoglobin
A1c level was 6.8% and her physician started her on empa-
glifozin and pioglitazone.
She reported feeling depressed and lined up 10 full
vials of insulin glargine (1,000 units each), then she filled
up 100 U-100 syringes and injected them into multiple
sites primarily in the anterior abdominal wall. She woke
up 36 hours later and did not recall anything after the over-
dose. She called her father who then notified the emergen-
cy medical services who found her in a state of profound
hypoglycemia. The patient’s glucometer read “very low,”
which meant her blood glucose level was between 0 to 12
mg/dL according to the package insert. She was given a
bolus of dextrose 50% (D50) intravenously and taken to
the emergency room of the outside facility where the initial
blood glucose reading was 22 mg/dL. The patient was
drowsy; she required multiple boluses of D50, was started
on a dextrose 5% drip, and was transferred to the intensive
care unit at our hospital.
On admission to the intensive care unit (49 hours after
the overdose), the patient’s blood glucose was 41 mg/
dL despite 4 ampules of D50 given by emergency medi-
cal services en route. Upon exam the abdominal wall was
found to be unremarkable with no areas of fluctuance or
induration at the injection sites to suggest delayed absorp-
tion of insulin. The dextrose 5% infusion was immediately
changed to dextrose 10% at 150 mL/h, and a glucagon drip
at 1 mg/h was also added. Lab analyses showed her potas-
sium level was 2.8 mmol/L, creatinine was 1.34 mg/dL,
aspartate aminotransferase was 60 U/L, and alanine amino-
transferase was 62 U/L. The patient was later found to have
hepatitis C. The patient’s insulin level was >3000 μIU/mL
(the reference range is 4.0 to 13.1 μIU/mL).
During the first 12 hours in the intensive care unit,
the patient continued to have blood sugar levels as low
as 36 mg/dL requiring multiple D50 boluses, hence the
infusion was increased to dextrose 20% at 150 mL/h via a
central line.
In the next 12 hours, with no change in dextrose
requirement, glucagon was considered ineffective and
discontinued. Octreotide was started using a 100-μg,
subcutaneous injection followed by a drip at 50 μg/h to
prevent any insulin release by the pancreas in response
to the dextrose being given. The patient’s mental status
improved as she was no longer drowsy and a liberal carbo-
hydrate diet was started along with a cornstarch slurry, but
dextrose requirements remained high.
During the second day of admission, the rate of 20%
dextrose administration was increased to 300 mL/h, but
she continued to have hypoglycemic episodes with blood
glucose as low as 49 mg/dL despite being on both intra-
venous dextrose and octreotide. Therefore, steroids were
initiated (Fig. 1) and 100 mg of hydrocortisone was given
intravenously every 6 hours. Soon after the first steroid
dose, her blood glucose went up to 205 mg/dL.
During the third day in the intensive care unit the
patient’s dextrose drip was closely titrated and was
weaned off. Her insulin level was down to 118.5 μIU/mL.
Octreotide treatment was also stopped. Hydrocortisone
administration was tapered down to 100 mg every 12 hours.
At approximately 125 hours after the overdose, the patient
had another hypoglycemic episode and was restarted on an
infusion of 10% dextrose. Her insulin level at the time was
48.8 mIU/mL. Hydrocortisone was changed to methylpred-
nisolone for longer duration of action as well as enhanced
glucocorticoid effect.
On the fifth day in the intensive care unit, the insulin
level decreased to 29.4 μIU/mL, liberal oral carbohydrates
were continued, and dextrose infusion was stopped at 150
hours after the overdose. The patient was still closely moni-
tored, but she had no more episodes of hypoglycemia and
was transferred to the psychiatric unit on day 6. Linagliptin
(at 5 mg/d) was started for her type 2 diabetes mellitus after
another week of inpatient blood sugar monitoring at the
psychiatric unit.
DISCUSSION
Insulin glargine overdose can lead to prolonged hypo-
glycemia. Neurogenic symptoms like tremors and sweating
or neuroglycopenic symptoms such as confusion, perma-
nent cognitive dysfunction, coma, and ultimately death can
occur (16). Electrolyte abnormalities like hypokalemia,
hypophosphatemia, and hypomagnesemia have also been
noted. Massive amounts of dextrose-containing fluids are
given intravenously which can cause fluid overload and
lead to pulmonary edema. It has also been reported that
massive glucose supplementation may lead to acute liver
injury (1,3).
Monitoring insulin levels can be a useful tool in deter-
mining the ongoing dextrose requirements (14). This may
also prevent recurrent hypoglycemia due to premature
cessation of dextrose infusion.
Case reports of insulin glargine overdose in the litera-
ture (Table 1) have shown that the hypoglycemia can persist
for several days, and comorbidities like renal or hepatic
e72 Steroids in Insulin Overdose, AACE Clinical Case Rep. 2018;4(No. 1)
Fig. 1. Blood glucose levels over time starting from first presentation (line graph) as well as grams of dextrose infused per hour
including additional dextrose boluses (bar graph).
dysfunction may further reduce insulin metabolism. In the
reported cases, insulin glargine doses used ranged between
26 to 4,800 units; some of the patients also co-injected
insulin aspart. The duration of hypoglycemia varied from
40 to 130 hours. Treatment modalities used included liber-
al amounts of intravenous dextrose, glucagon, octreotide,
and excision of insulin depots.
Glucagon can be used for hypoglycemia as it
promotes glycogenolysis and gluconeogenesis provided
there are enough glycogen stores. Given that our patient
came into our care nearly 48 hours after the overdose, it
is likely that her glycogen stores were already depleted.
We initially started our patient on glucagon but, as no
effect was observed on the blood glucose levels, it was
soon discontinued.
Octreotide has been previously used successfully in
treating poisoning with oral hypoglycemic agents and,
although it has been used in insulin overdoses with the aim
of suppressing endogenous insulin secretion (1), in this
case we did not observe much difference in total glucose
requirement after starting octreotide.
Corticosteroids are known for their hyperglycemic
effects. In one study, the majority of patients receiving the
equivalent of 40 mg prednisone daily developed hypergly-
cemia in just 2 days (17). The mechanism of hyperglyce-
mia is predominantly decreased insulin sensitivity in target
tissues leading to insulin resistance. In the liver it results in
increased basal glucose production, and in the periphery,
Copyright © 2018 AACE
especially the adipose and skeletal tissues, glucose use is
impaired (18). Glucocorticoids decrease insulin-mediated
glucose uptake by inhibiting glucose transporter type 4.
Additionally they increase fatty acid release into the blood
from the liver which further interferes with glucose utili-
zation, especially by skeletal muscles (18-20). They can
also cause beta cell dysfunction in the pancreas leading to
an inability to release insulin. In this case the hyperglyce-
mic effects of glucocorticoids were seen in just a few hours
after administration. The drop in blood glucose seen on day
4 after stopping the dextrose infusion was thought to be
secondary to premature tapering of the steroid dose. In our
patient, when hydrocortisone was changed to methylpred-
nisolone, it stabilized the blood sugar better.
Another reported treatment involves excision of the
insulin depot from the subcutaneous tissue if a large area
of fluctuance is apparent (3,4). Hemodialysis is also known
to remove insulin from the blood and theoretically could be
used if fluid overload is a concern, but it has not yet been
used in cases of insulin overdose. Raw cornstarch has been
also used to prevent nocturnal hypoglycemia using 1.5 g/
kg body weight mixed in water and given at bedtime and
every 3 hours (15) as it slowly releases glucose.
CONCLUSIONS
Clinicians should be aware that a massive insulin
glargine overdose requires prompt intensive care, frequent
Copyright © 2018 AACE Steroids in Insulin Overdose, AACE Clinical Case Rep. 2018;4(No. 1) e73

Table 1
Case Reports of Insulin Glargine Overdose
Duration of
Reference Time elapsed Initial dextrose Insulin levels Treatment
number Age/sex Insulin dose since overdose blood glucose infusion at presentation modalities
300 U IG
(6) 33-year-old female 15 hours 38 mg/dL 40 hours Not checked D5, D10, and D50
200 U IA
(7) 21-year-old female 26 U IG 2.5 hours 16 mg/dL 60 hours Not checked D10 and D50
300 U IG
(8) 22-year-old female 4 hours Undetectable 59 hours Not checked D20 and D30
300 U IA
(9) 55-year-old female 100 U IG 20 minutes 134 mg/dL None Not checked Managed at home
D5, D10, D25,
(10) 37-year-old male 150 U IG 5 hours 15 mg/dL >48 hours Not checked
and D50
(11) 31-year-old female 1,000 U IG 3 hours 43 mg/dL 130 hours Not checked D5 and D10
(12) 51-year-old female 2,700 U IG 16 hours 23 mg/dL 120 hours Not checked D10 and D50
800 U IA
(14) 39-year-old male Not reported 50 mg/dL 81 hours 3,712 μU/mL D5 and D10
3,800 U IG
D10, D20,
(15) 12-year-old female 2,000 U IG 1-2 hours 25 mg/dL 130 hours Not checked
and cornstarch
(13) 76-year-old male 500 U IG Not reported 30 mg/dL 96 hours Not checked D10 and D50
1,200 U IG D50 and dextrose
(4) 18-year-old male 50 minutes 41 mg/dL 67 hours 4,220 pmol/L
600 U IA excision
D10, D20,
(3) 26-year-old male 4,800 U IG A few hours 67 mg/dL Not reported Not checked and dextrose
excision
D5, D10, D50,
(1) 56-year-old male 3,300 U IG 1-1.5 hours 64 mg/dL >100 hours Not checked
and octreotide
Dextrose and
(5) 45-year-old male 3,600 U IG Not reported 20 mg/dL 120 hours Not checked
glucagon
1,500 U IG
(2) 43-year-old male 5 hours 30 mg/dL 115 hours <400 pg/mL D20 and D50
600 U IA
900 U IG
(2) 43-year-old male 3 hours 49 mg/dL 96 hours Not detected D20 and D50
600 U IA
D5, D10, D20,
Present D50, glucagon,
36-year-old female 10,000 U IG 44 hours 0-12 mg/dL 150 hours >3,000 μU/mL
case octreotide,
and steroids
Abbreviations: D = dextrose (following number represents percent level of infusion); IA = insulin aspart; IG = insulin glargine; U = units.

blood sugar monitoring, aggressive electrolyte replace- DISCLOSURE

ment, and a prolonged dextrose infusion well beyond what
would be expected from the pharmacokinetic properties of
the insulin preparation. Octreotide has been previously used
with success as an adjunct to dextrose for hypoglycemia
associated with sulfonylurea overdose. Given the results
in this patient, we propose an earlier initiation of glucocor-
ticoids for treatment of insulin overdose as octreotide has
stronger rationale in sulfonylurea-induced hypoglycemia
than in cases of insulin overdose. Steroids may prove to be
especially helpful in cases where adverse effects such as
fluid overload and pulmonary edema are a concern due to
the large amount of dextrose given intravenously.
A.M.D.Q. serves on the Speakers Bureau for Sanofi-
Aventis and Janssen. The other authors have no multiplic-
ity of interest to disclose.
REFERENCES
1. Groth CM, Banzon ER. Octreotide for the treatment of hypo-
glycemia after insulin glargine overdose. J Emerg Med. 2013;45:
194-198.
2. Kim CCK, Rosano TG, Chambers EE, Pai MP, Desemone J.
Insulin glargine and insulin aspart overdose with pharmacokinetic
analysis. AACE Clin Case Rep. 2016;2:e122-e128.
e74 Steroids in Insulin Overdose, AACE Clinical Case Rep. 2018;4(No. 1)
3. Warriner D, Debono M, Gandhi RA, Chong E, Creagh F.
Acute hepatic injury following treatment of a long-acting insulin
analogue overdose necessitating urgent insulin depot excision.
Diabet Med. 2012;29:232-235.
4. Droste J, Hundia V, Pettit A, Narayan N, Nejim A. Excision of
injection site substantially reduced serum insulin concentration in
a potentially life-threatening insulin analogue overdose. Practical
Diabetes. 2012;29:243-245.
5. Karatas F, Sahin S, Karatas HG, Karsli PB, Emre C,
Kivrakoglu F. The highest (3600 IU) reported overdose of
insulin glargine ever and management. Indian J Crit Care Med.
2015;19:750-751.
6. Tofade TS, Liles EA. Intentional overdose with insulin glargine
and insulin aspart. Pharmacotherapy. 2004;24:1412-1418.
7. Brvar M, Mozina M, Bunc M. Poisoning with insulin glargine.
Clin Toxicol. 2005;43:219-220.
8. Fromont I, Benhaim D, Ottomani A, et al. Prolonged glucose
requirements after intentional glargine and aspart overdose.
Diabetes Metab. 2007;33:390-392.
9. Kuhn B, Cantrell L. Unintentional overdose of insulin glargine.
Am J Health Syst Pharm. 2008;65:508.
10. Fuller ET, Miller MA, Kaylor DW, Janke C. Lantus over-
dose: case presentation and management options. J Emerg Med.
2009;36:26-29.
11. Ashawesh K, Padinjakara RN, Murthy NP, Nizar H, Anwar
A. Intentional overdose with insulin, glargine. Am J Health Syst
Pharm. 2009;66:534.
Copyright © 2018 AACE
12. Lu M, Inboriboon PC. Lantus insulin overdose: a case report. J
Emerg Med. 2011;41:374-377.
13. Doğan FS, Onur ÖE, Altınok AD, Güneysel Ö. Insulin glargine
overdose. J Pharmacol Pharmacother. 2012;3:333-335.
14. Mork TA, Killeen CT, Patel NK, Dohnal JM, Karydes HC,
Leikin JB. Massive insulin overdose managed by monitoring
daily insulin levels. Am J Ther. 2011;18:e162-e166.
15. Kumar A, Hayes CE, Iwashyna SJ, et al. Management of inten-
tional overdose of insulin glargine. Endocrinol Nutr. 2012;59:
570-572.
16. Vue MH, Setter SM. Drug-induced glucose alterations part
1: Drug-induced hypoglycemia. Diabetes Spectrum. 2011;24:
171-177.
17. Donihi AC, Raval D, Saul M, Korytkowski MT, DeVita MA.
Prevalence and predictors of corticosteroid-related hyperglycemia
in hospitalized patients. Endocr Pract. 2006;12:358-362.
18. Hwang JL, Weiss RE. Steroid-induced diabetes: a clinical and
molecular approach to understanding and treatment. Diabetes
Metab Res Rev. 2014;30:96-102.
19. Kwon S, Hermayer KL. Glucocorticoid-induced hyperglycemia.
Am J Med Sci. 2013;345:274-277.
20. Clore J, Thurby-Hay L. Glucocorticoid-induced hyperglycemia.
Endocr Pract. 2009;15:469-474.