Published: 4 June 2026

Publications

Insulin autoimmune syndrome

Published: 4 June 2026
Prescriber Update 47(2): 29–30
June 2026

Medsafe recently reviewed the risk of insulin autoimmune syndrome with captopril and requested the sponsor to update their data sheet with information about the syndrome. This article briefly describes insulin autoimmune syndrome and medicines associated with it.

What is insulin autoimmune syndrome (IAS)?

IAS is a rare condition characterised by recurrent hypoglycaemic episodes, elevated serum insulin and positive insulin autoantibodies. Unlike other forms of hypoglycaemia, classical IAS occurs in the absence of exogenous insulin administration.¹

The triggers associated with developing IAS include medicines, viruses (eg, measles, mumps, rubella, varicella zoster) and haematological conditions (eg, multiple myeloma).²

Under normal physiological conditions, insulin is secreted from the pancreas in response to increased blood glucose after eating. Insulin promotes uptake of glucose by cells resulting in a normalisation of blood glucose levels.

In IAS, the presence of insulin autoantibodies disrupts this process by binding to insulin. The autoantibodies have a high binding capacity for insulin which means each autoantibody can bind several insulin molecules, forming large complexes. When insulin is bound it is unable to exert its normal glucose-lowering effect.^1,2

However, while the autoantibodies have a high binding capacity, they also have a low affinity for insulin. This means that insulin is not tightly bound to the autoantibody and can dissociate (detach) from the complex unpredictably. This increases the free insulin in the circulation, leading to recurrent episodes of hypoglycaemia.^1,2

There appears to be a genetic predisposition to IAS associated with variation in the human leukocyte antigen (HLA) system, particularly the DRB1*0406 allele.² The DRB1*0406 genotype is more common in East Asian populations, which may partly explain why IAS occurs more frequently in East Asians than Caucasians.¹

Medicines associated with IAS

Medicines are a common trigger of IAS, with about half of cases thought to be medicine-induced.^1,3

Medicines and active metabolites that contain a sulfhydryl group (-SH) or thiol group (R-SH) have been associated with IAS. Examples include carbimazole, clopidogrel and captopril.^1,2

It is thought these medicines bind and cleave the sulfhydryl bonds between insulin chains making endogenous insulin more immunogenic. This ultimately results in the formation of insulin autoantibodies.^1,2

IAS has also been reported with other medicines, but the mechanism is unclear.

Treatment and prognosis

IAS, although serious, is a self-limiting condition with insulin autoantibodies generally resolving on their own within a few months.¹ Management may include stopping the causative medicine and supportive treatment, such as dietary modifications (eg, small frequent meals with low carbohydrate content) to reduce the risk of hypoglycaemia.^1,2

References

1. Lin M, Chen Y and Ning J. 2023. Insulin autoimmune syndrome: A systematic review. International Journal of Endocrinology 2023(Feb 15): 1225676. DOI: 10.1155/2023/1225676 (accessed 2 April 2026).
2. Cappellani D, Macchia E, Falorni A, et al. 2020. Insulin autoimmune syndrome (Hirata disease): A comprehensive review fifty years after its first description. Diabetes Metabolic Syndrome and Obesity 13: 963-78. DOI: 10.2147/dmso.S219438 (accessed 2 April 2026).
3. Zhang H, Yuan MX and Pan Q. 2025. Insulin autoimmune syndrome: A Chinese expert consensus statement. Aging Medicine 8(1): e70007. DOI: https://doi.org/10.1002/agm2.70007 (accessed 2 April 2026).