Current pregnancy, alcohol abuse, and use of short-acting insulin were found to be among the strongest risk factors for severe hypoglycemia among adults with insulin-treated type 2 diabetes (T2D), according to the results of a study published in Diabetes, Obesity and Metabolism.

Researchers sought to identify factors — in addition to those already established — associated with increased risk for severe hypoglycemia that resulted in emergency medical treatment among patients with insulin-treated T2D.

The retrospective, nested, case-control study was conducted with use of data from IQVIA PharMetrics Plus, a large US administrative health care claims database. All patients with at least 1 insulin prescription claim from July 1, 2012, to December 31, 2018, were identified. Control individuals were selected with use of incidence-density sampling.

A total of 3153 case-control pairs were included. The median age of case participants was 57 years (range, 18-84), and 52.0% were men. The median age of the control group was 57 years (range, 19-84), and 55.3% were men. The mean (SD) time of being at risk before the initial severe hypoglycemia event was 11.2 (13.8) months.

The following risk factors were found to have the strongest independent association with severe hypoglycemia: current pregnancy (odds ratio [OR], 3.20, P =.0003); alcohol abuse (OR, 2.43, P <.0001); use of short or rapid-acting insulin (OR, 2.22, P <.0001); having a cancer diagnosis 1 month prior to the index date (OR, 1.87, P <.0001); having dementia or Alzheimer disease (OR, 1.73, P =.0175); having peripheral vascular disease (OR, 1.59, P <.0001); use of an antipsychotic agent (OR, 1.59, P =.0059); use of antianxiety medication (OR, 1.51, P =.0012); having paralysis, hemiplegia, or paraplegia (OR, 1.51, P =.0416); and having hepatitis (OR, 1.50, P =.0303).

The long-term use of β-adrenoceptor agonists and the current use of noninsulin glucose-lowering medications were associated with reduced odds of severe hypoglycemia.

A diagnosis after introduction of the International Classification of Diseases–10 coding system (October 1, 2015, or later) was associated with more than twice the odds of having severe hypoglycemia (OR, 2.13, P <.0001).

Among several study limitations, the administrative claims database included data collected for billing purposes instead of research, and medication use was based on pharmacy claims. In addition, the findings are limited by the absence of information regarding behavioral, dietary, and socioeconomic factors that may be associated with severe hypoglycemia.

“Clinicians should take a detailed clinical history that includes documentation of comorbid conditions occurring during the previous six months and either recent or current medication usage, if they are to identify “high-risk” patients,” advised the researchers. “Therapeutic regimens and individualized targets may have to be modified in the presence of factors highlighted in the present study.”

Disclosure: This study was funded by Eli Lilly and Company. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Settles J, Kan H, Child CJ, et al. Previously unrecognised risk factors for severe hypoglycaemia requiring emergency medical care in insulin-treated type 2 diabetes: results from a real-world nested case-control study. Diabetes Obes Metab. Published online March 9, 2022. doi:10.1111/dom.14690