Hypersensitivity reactions to human insulin analogs in insulin-naïve patients: a systematic review

The objective of this study was to raise awareness of hypersensitivity reactions to human insulin analogs (HIAs) in insulin-naïve patients and encourage consistent and detailed reporting of HIA reactions.

A search of PubMed, MEDLINE and International Pharmaceutical Abstracts using the terms 'insulin' and 'hypersensitivity' was completed with English language, humans, and publication date after 1 January 1990 as limits.

The initial search identified 598 articles. These titles and abstracts were reviewed for relevance (e.g. mention of HIA) resulting in the exclusion of 477 articles. The full texts of the remaining titles were evaluated in addition to each article's references to identify additional reports meeting criteria (n = 14). Upon extensive review, 118 articles were excluded for not meeting prespecified inclusion criteria, resulting in 17 articles.

Evidence supporting hypersensitivity reactions to HIAs was variable, potentially due to a variety of causes (e.g. difficulty identifying a true case of hypersensitivity reaction to HIAs). Inconsistencies were noted for the identification, confirmatory testing, management, and reporting of these reactions. Management strategies included use of insulin desensitization protocols, antihistamines, steroids, immunosuppressant/immunomodulator therapies, conversion to noninsulin therapies, and pancreas transplantation.

Complete and consistent identification, evaluation, management, and reporting of these reactions is essential. Specific aspects of the patient's history should be reported, including previous insulin exposure, the specific HIAs used, duration of use prior to the reaction, a clear timeline of the reaction, and discussion of precipitating events or confounding factors.