The Journal of Emergency Medicine, Vol. 43, No. 3, pp. 435–437, 2012Copyright � 2012 Elsevier Inc.

Printed in the USA. All rights reserved0736-4679/$ - see front matter

doi:10.1016/j.jemermed.2011.06.038

RECEIVED: 24 NACCEPTED: 4 Jun

ClinicalCommunications: Adults

INTRAVENOUS OVERDOSE OF INSULIN GLARGINE WITHOUT PROLONGEDHYPOGLYCEMIC EFFECTS

Stephen Thornton, MD* and Scott Gutovitz, MD†

*Department of Emergency Medicine, University of California, San Diego Medical Center, San Diego, California and †Departmentof Emergency Medicine, University of Kansas Medical Center, Kansas City, Kansas

Reprint Address: Stephen Thornton, MD, Department of Emergency Medicine, University of California, San Diego Medical Center,200 West Arbor Drive, #8925, San Diego, CA 92103-8925

, Abstract—Background: Insulin glargine is a long-actinginsulin that can cause prolonged hypoglycemia when mis-dosed or overdosed subcutaneously. There are no reportsof intravenous overdoses of insulin glargine. Objectives:We present a case of a patient inadvertently given a large in-travenous dose of insulin glargine (100 units) who had an un-remarkable course. Case Report: A 46-year-old woman witha history of type 2 diabetes was found to be hyperglycemicand was mistakenly given an intravenous bolus of 100 unitsof insulin glargine. She did not become hypoglycemic, didnot require parenteral dextrose, and her blood sugar read-ings stabilized within 3 h. She was admitted and observedfor 17 h and discharged without complication. Conclusion:To our knowledge, this is the first report of a significantintravenous insulin glargine administration. This patienthad an unremarkable course and recovered without anyparenteral glucose. This case, along with prior studies onhealthy volunteers, suggests that unlike subcutaneous over-doses, intravenous insulin glargine misdose/overdose maynot need prolonged observation; an observation time of6 hmay be sufficient in these patients. � 2012 Elsevier Inc.

, Keywords—insulin glargine; overdose; intravenous;medication error

INTRODUCTION

Insulin glargine is a long-acting insulin that was intro-duced in 2000. It has properties that make it unique

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among the many forms of insulin available for the treat-ment of diabetes. It has an extended duration of action(>24 h) and no measurable peak effect (1). It is due tothis long duration of action that overdoses of insulinglargine can be problematic, often requiring hospitaladmissions and prolonged treatment (2–8). All priorreports of insulin glargine overdoses and toxicity haveconcerned exposure via the subcutaneous route. To ourknowledge, there are no reports in the literature ofinadvertent or intentional overdoses of insulin glarginegiven intravenously. We present a case of a patient whowas inadvertently given a large intravenous insulinglargine bolus, with an unremarkable hospital course.

CASE REPORT

A 46-year-old woman with multiple medical problemsincluding a history of type 2 diabetes mellitus, chronicmigraine headaches, fibromyalgia, hypertension, hyper-lipidemia, gastroparesis, and depression presented tothe Emergency Department (ED) complaining of head-ache, nausea, vomiting, and blurred vision, which wastypical for her prior migraine episodes. During her eval-uation it was noted that she had a finger stick blood sugarof 435 mg/dL at 4:56 p.m. There was no laboratoryevidence of diabetic ketosis or ketoacidosis. Her homemedication list included insulin aspartate 4 units subcuta-neously three times daily with meals, and insulin glargine

arch 2011;

Figure 1. Finger stick blood sugar vs. time; insulin glargineinjection occurred at time = 0 h.

436 S. Thornton and S. Gutovitz

100 units subcutaneously at bedtime. The physicianordered the patient to receive 100 units of insulin glarginesubcutaneously. At 10:15 p.m. the nurse inadvertentlygave the 100 units of insulin glargine intravenously.This medication error was immediately noted by thenurse, and the pharmacy was consulted and advised thatthe patient be admitted for observation and serial bloodglucose monitoring. Poison control was not contacted.At 10:37 p.m., the patient’s finger stick blood sugar was291 mg/dL, at 11:14 p.m. it was 207 mg/dL, and at11:59 p.m. it reached a nadir of 158 mg/dL. The patienthad a meal at 12:15 a.m. No parenteral glucose was givenin the ED. The patient was admitted and her blood sugarremained elevated during her entire hospital stay(Figure 1). She was observed for a total of 17 h afteradministration of the insulin glargine and discharged instable condition. She never required any parenteralglucose while in the hospital. In fact, she was placedback on her regular insulin aspartate dose within 12 hof the accidental intravenous insulin glargine dose.

DISCUSSION

Diabetes is one of the most common chronic diseases in theUnited States. It is estimated to affect as much as 13.7% ofmen and 11.7% of women (9). Insulin is one of the maintreatment modalities of diabetes, and insulin glargine isthemost widely prescribed analogue of insulin (10). Insulinglargine is unique among the currently available insulinpreparations in that it has a long duration of activity andnodiscernible peak effect. These properties are due to a sub-stitution of the #21 amino acid residue on A chain with gly-cine, and the addition of 2 arginine residues to the B chain(11). The result is a shift in the isoelectric point, makinginsulin glargine less soluble in neutral or alkaline solutions.Subsequently, when injected subcutaneously, insulinglargine forms microprecipitates, and these are slowlyabsorbed. The tendency of insulin glargine to form hexam-ers and the addition of zinc also serve to extend absorptiontime (11). It is precisely due to these properties that subcu-taneous overdoses of insulin glargine are reported to causeprolonged hypoglycemia, frequently requiring large dosesof parenteral glucose (2–8). In one report, hypoglycemiawas noted 106 h after overdose of 1000 units of insulinglargine (7). Another case required 460 grams of parenteralglucose over 48 h (2). However, as our case illustrates,insulin glargine behaves much differently when injectedintravenously. This has been suggested by several healthyvolunteer studies. In one study of 20 healthy subjects,a 0.1-IU/kg insulin glargine intravenous infusion over30 min was found to be equipotent to a 0.1-IU/kg regularhuman insulin 30-min intravenous infusion whencomparing glucose infusion rates, suppression of serumC-peptide, and duration of action (12). Another study of

15 healthy volunteers given 40-mU/m2 intravenous infu-sions of either insulin glargine or regular human insulinfound no difference when comparing endogenous glucoseoutput or peripheral glucose disposal. They came to theconclusion that insulin glargine’s unique clinical propertiesare due to its absorption kinetics (13). It is important to notethat both of these prior studies investigated infusions ofinsulin glargine and not a large single bolus such as oc-curred in this case. The patient we describe received an in-travenous bolus dose of 0.77 units/kg, and she seemed tohave a peak clinical effect at approximately 105 min afterinjection. Prior studies indicate that an intravenous bolusof regular insulin seems to have a peak hypoglycemic effectaround 30 min, though this may be prolonged to 90 minin patients with diabetes (14,15). Therefore, althoughintravenous dosing of insulin glargine does not seem tobe associated with the prolonged hypoglycemia that isseen with the subcutaneous route, it may have a longerclinical effect than intravenous regular human insulin.

CONCLUSION

To our knowledge, this is the first report of a significantintravenous insulin glargine administration. This patienthad an unremarkable course and recovered without anyparenteral glucose. Although further verification isneeded, this case, along with prior studies on healthyvolunteers, suggests that unlike subcutaneous overdoses,intravenous insulin glargine misdose/overdose may notneed prolonged observation, and an observation time of6 h may be sufficient in these patients.

Acknowledgment—The authors thank Chris Tomaszewski, MD,for his assistance and support.

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