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Hypersensitivity reactions to insulins

Lucie Heinzerling, MD, PhD, MPH
Section Editors
N Franklin Adkinson, Jr, MD
David M Nathan, MD
Deputy Editor
Anna M Feldweg, MD


Several types of hypersensitivity reactions to insulin preparations have been described. These reactions may be caused by the insulin itself or by additives within the preparation. Hypersensitivity reactions to insulin are rare with human insulins and insulin analogues. However, some types are serious and even life-threatening and may have a significant detrimental impact on the patient's diabetic management. Evaluation requires close collaboration with endocrinology and allergy experts.

The clinical manifestations, classification, diagnosis, and management of hypersensitivity reactions to insulin preparations are discussed in this topic review. Other adverse effects of insulin therapy are discussed separately. (See "General principles of insulin therapy in diabetes mellitus", section on 'Safety'.)


Hypersensitivity to insulin can occur in all age groups and in patients with either type 1 or type 2 diabetes.

Hypersensitivity reactions to the human insulins and insulin analogues used today are rare, although comprehensive epidemiologic studies are lacking. Estimates of incidence range from 0.1 to 3 percent of patients [1-3]. In contrast, insulin hypersensitivity was more common when relatively impure and heterologous porcine and bovine insulins were widely used, as these are far more immunogenic. The progressive improvement in purification of nonhuman insulins, use of single animal species insulins, and the nearly universal adoption of highly purified human insulins beginning in the 1980s, all contributed to the reduction in injection site and systemic allergic reactions to insulin.


When first approaching a patient with possible insulin hypersensitivity, the history should focus on the rapidity with which the signs and symptoms develop after injection (ie, within minutes to one hour versus later) to distinguish immediate from delayed reactions, the presence or absence of systemic symptoms to judge the severity, and whether the reactions have become worse over time. If signs and symptoms are limited to the skin, the injection site and the rest of the integument should be carefully examined. In most cases, skin changes that are suspected to be a manifestation of insulin hypersensitivity have other causes, such as injection site irritation or a separate dermatologic condition, such as prurigo nodularis simplex subacuta or atopic dermatitis. (See 'Injection site irritation' below and 'Differential diagnosis' below.)

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Literature review current through: Nov 2017. | This topic last updated: Mar 17, 2016.
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