Insulin glargine (Lantus; Aventis, Parsippany, NJ) is a recently available basal insulin analog that appears to have a more consistent activity profile than comparable long-acting insulin products (1). It is typically administered as a single injection before bedtime. Due to minor modification of the amino acid sequence in both the A- and B-chains of the insulin molecule, glargine is soluble only in an acidic pH (2). When injected, glargine precipitates in the neutral pH of subcutaneous tissues, prolonging its systemic absorption (2). Clinical trials have demonstrated that compared with NPH insulin, glargine improves fasting glucose in patients with type 1 diabetes (3) and results in less nocturnal hypoglycemia in patients with both type 1 (4) and type 2 (5) diabetes. It may be particularly useful in individuals who demonstrate labile blood glucose control with conventional insulin formulations. One immediately obvious difference between glargine and other long- (or intermediate-) acting insulins is that the product is a clear solution, similar to short-acting products, not a semi-opaque suspension. To avoid confusion with such insulins, Lantus is marketed in a vial of unique shape, taller and thinner than all other insulin vials, and the label contains purple print. We herein report, however, our recent experience with two patients who mistakenly administered a rapid-acting insulin analog in lieu of their usual glargine dose.
The first patient is a 25-year-old woman with type 1 diabetes duration of 6 years. She had generally been under good control, with a recent HbA1c of 7.0% (normal range 4.3–6.4%). There was no history of diabetes-related complications, including retinopathy or other medical conditions, and her compliance had always been excellent. Her regimen included insulin glargine, 22 units nightly at bedtime plus adjusted-dose insulin lispro (Humalog; Eli Lilly, Indianapolis, IN) before meals, which she had been using for the previous 2 months without difficulty. On 14 October 2001, she accidentally drew her scheduled bedtime dose of 22 units from her lispro vial rather than her glargine vial, realizing her error only after it had been administered. At that time, her blood glucose measured 160 mg/dl on a home glucose meter. The patient was instructed to preemptively consume carbohydrate calories, but her intake was limited because of nausea. By 90 min after the injection, her blood glucose measured 90 mg/dl, and by 2 h, it had dropped to 57 mg/dl. She was, at that point, referred to the emergency ward, where intravenous dextrose was adminstered to reverse her hypoglycemia. Five hours after the insulin injection, her blood glucose stabilized in the 160 mg/dl range.
The second patient is a 52-year-old female college professor with type 1 diabetes duration of almost 40 years. Her control was fair, with a recent HbA1c of 7.4%, on a regimen of 17 units glargine (started 3 months previously), administered in the morning, plus adjusted-dose lispro before meals, which she took by separate injection. There was no history of diabetes-related complications or any other significant medical disorders. Her compliance had been excellent. On the morning of 16 October 2001, she inadvertently injected 17 units lispro instead of glargine. At the time of administration, her blood glucose was 315 mg/dl, at which point she would have normally taken 5 units lispro. Despite eating nearly continuously for the subsequent 3 h, her blood glucose dropped to as low as 67 mg/dl and finally stabilized in the 85 mg/dl range. No further intervention was required.
These cases serve to underscore a significant new risk that may be associated when insulin glargine is used in combination with short-acting insulins (regular, lispro, and aspart). Before the availability of glargine, the distinction between long- (or intermediate-) acting insulins and short-acting insulins was obvious, with the former being cloudy in appearance, whereas the latter was clear. We propose that these patient errors occurred because of the similarity in appearance between glargine and short-acting insulins, despite glargine’s unique vial shape and label. It should be noted that the two patients in whom these episodes occurred had normal cognitive function, no visual impairment, and had previously demonstrated impeccable compliance. In addition, they had been counseled about the likeness in appearance between their two insulin products at the initiation of glargine therapy. Despite this, both admitted that it was indeed the similarity between their insulins, glargine and lispro, that led to the confusion.
We recommend that patients should be made aware of the potential danger of confusing glargine with their short-acting insulins and educated in strategies to help avoid such accidents. We also recommend that the manufacturer of glargine insulin, Aventis Pharmaceuticals, in cooperation with the Food and Drug Administration, consider further alternative packaging or perhaps even solution tinting to more easily distinguish it from the widely used short-acting preparations.
References
Address correspondence to Silvio E. Inzucchi, Endocrinology, TMP 534, Yale University School of Medicine, Box 208020, New Haven, CT 06520. [email protected].
G.R.S. is a member of an advisory board for and has received honoraria from Aventis. S.E.I. is a member of an advisory board for and has received honoraria from Eli Lilly and Aventis and has received grant support from Eli Lilly.
