Half of T2D Patients on Insulin Make Insulin Antibodies

Marlene Busko

March 09, 2022

Researchers published the  study covered in this summary on Research Square as a preprint that has not yet been peer reviewed.

Key Takeaways

  • In a retrospective, cross-sectional study of 1863 Chinese patients with type 2 diabetes who received insulin roughly half developed clinically meaningful levels of insulin antibodies, and this status linked with worse outcomes.

  • Elderly nonsmokers with higher levels of low-density lipoprotein cholesterol had especially increased risk for developing insulin antibodies.

  • Patients with a positive insulin antibody level (greater than 5%) had significantly higher fasting plasma glucose levels and a significantly higher level of insulin resistance compared with the patients who were negative for insulin antibodies.

  • The study confirmed, for the first time in such a large population, that insulin glargine induced fewer positive insulin antibody responses than other insulin regimens.

  • Treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, and insulin secretagogues each linked with fewer patients having positive levels of insulin antibodies.

Why This Matters

  • Patients with type 2 diabetes who take insulin commonly form insulin antibodies that tend to bind and/or release insulin in unpredictable ways that can hamper glycemic control, and higher levels of insulin antibodies are associated with increased risks of hypoglycemia, diabetes complications, and earlier mortality.

  • The results confirmed that insulin glargine induced less insulin antibodies than other insulin regimens, and showed this for the first time in a large population.

  • The findings suggest that all patients with type 2 diabetes who are on insulin should have a test to determine if they are positive for insulin antibodies, especially elderly, nonsmoking patients who also have a lipid metabolic disorder.

  • Clinicians should consider treating patients with type 2 diabetes who require insulin with glargine and DPP-4 inhibitors, metformin, or insulin secretagogues to try to minimize the risk of insulin antibodies.

Study Design

  • The researchers retrospectively analyzed 2496 consecutive patients with type 2 diabetes and treated with insulin seen at a center in China during 2017 and 2018. They focused on 1863 patients with data available on their insulin antibody status who also met certain inclusion criteria.

  • The patients were taking one of nine types of insulin, and several patients were also on stable treatment with one or more oral antidiabetic drugs.

  • Patients underwent an insulin antibody test that used radioactive iodine and scored positive when the percentage of bound to total 125-iodine in serum was greater than 5%.

Key Results

  • Close to half of the patients (48%) had a positive insulin antibody test.

  • Glargine was the most common insulin type, used by 29% of patients.

  • The prevalence of a positive insulin antibody test was lowest in patients who used glargine (32%) and highest in patients who used human insulin (70%, P < .001), and was 52% to 60% among patients who received other insulin forms (detemir, detemir plus aspart, aspart insulin, premixed human insulin, premixed lispro, or premixed aspart).

  • Patients with a positive insulin antigen test were older, had a longer diabetes duration, and higher total cholesterol, LDL-cholesterol, fasting blood glucose, insulin, and glutamate decarboxylase antibody levels and cancer rates, as well as lower alanine transferase and triglyceride levels and smoking rates, compared with other patients.

  • After adjusting for multiple variables, glargine significantly associated with the lowest insulin antibody levels (7%) and insulin aspart significantly linked to the highest insulin antibody levels (18%).

  • Insulin antibody levels were significantly lower in patients who used sulfonylureas/glinides, metformin, or DPP-4 inhibitors than in patients who used agents from other classes of oral antidiabetes drugs.


  • This was a cross-sectional study and hence cannot determine whether blood-glucose lowering drugs cause changes in insulin antibody levels; other factors such as duration of insulin use, age, and blood lipid levels may affect drug prescription and insulin antibody levels. 

  • The study focused on hospitalized patients who mostly had poor glycemic control. Correlations between insulin antibody levels and treatment with various glucose-lowering drugs in insulin-treated patients with good glycemic control needs further study.

  • Few patients received a sodium-glucose cotransporter 2 inhibitor, so the effect of agents in this class on insulin antibodies needs additional study.


  • The study did not receive commercial funding.

  • The authors report no relevant financial disclosures.

This is a summary of the preprint research study "Association between glucose-lowering drugs and circulating insulin antibodies induced by exogenous insulin therapy in patients with type 2 diabetes," by researchers from Nanging First Hospital, Nanjing Medical University, China. Preprints from Research Square are provided to you by Medscape Medical News. This study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com.

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