A high rate of non-severe hypoglycemic episodes (NSHEs) is associated with increased risk of severe hypoglycemia and major adverse cardiovascular events (MACE), according to analysis of data from the LEADER trial published in the journal Diabetologia.¹

In this post-hoc analysis of the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial, the researchers set out to investigate the association between the rate of episodes of non-severe hypoglycemia episodes (NSHEs) (plasma glucose level 56 mg/dL) and severe hypoglycemia in type 2 diabetes and/or major adverse cardiac outcomes including all-cause mortality.

The patients were grouped into three based on the rate of NSHEs: Group A (<2 NSHEs per year), Group B (2–11 NSHEs per year) and Group C (≥12 NSHEs per year). Occurrence of ≥2 episodes of NSHEs per year (Groups B and C) was found to be associated with higher rates of episodes of severe hypoglycemia with a hazard ratio of nearly 2 and 5, respectively compared to those who experienced <2 NSHEs every year.

Patients with higher annual rates of NSHEs (≥12 episodes per year) were also found to be associated with higher risk of MACE (HR 1.50), cardiovascular death (HR 2.08) and all-cause mortality (HR 1.80). No such correlation was observed in Groups A and B patients.

This long-term cardiovascular outcome trial has shown that type 2 diabetes patients who suffered high rates of NSHEs were at a higher risk of experiencing episodes of severe hypoglycemia later on. They were also vulnerable to adverse cardiovascular outcomes in terms of MACE, CV death including death from any cause. The authors therefore recommend that regardless of the cause of this association, treating physicians must identify such vulnerable patients to reduce NSHEs and prevent adverse CV complications.

Reference

1. Heller SR, et al. A higher non-severe hypoglycaemia rate is associated with an increased risk of subsequent severe hypoglycaemia and major adverse cardiovascular events in individuals with type 2 diabetes in the LEADER study. Diabetologia. 2022 Jan;65(1):55-64. doi: 10.1007/s00125-021-05556-7.