DEVOTE 3: temporal relationships between severe hypoglycaemia, cardiovascular outcomes and mortality

Area of Science:

• Cardiovascular medicine
• Endocrinology
• Clinical trials

Background:

• The Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) assessed cardiovascular safety.
• Severe hypoglycemia and all-cause mortality were secondary outcomes in DEVOTE.
• This analysis investigates the association between severe hypoglycemia and cardiovascular outcomes/mortality.

Purpose of the Study:

• To investigate the association between severe hypoglycemia and major adverse cardiovascular events (MACE).
• To determine the association between severe hypoglycemia and all-cause mortality in patients with type 2 diabetes.
• To evaluate the temporal relationship between severe hypoglycemia and subsequent MACE and mortality.

Main Methods:

• Secondary analysis of the DEVOTE trial data.
• Pooled population of patients with type 2 diabetes randomized to insulin degludec or insulin glargine.
• Time-to-event analyses used severe hypoglycemia as a time-dependent variable.

Main Results:

• No significant difference in MACE risk between patients with and without severe hypoglycemia (HR 1.38, p=0.080).
• Significantly higher risk of all-cause mortality in patients who experienced severe hypoglycemia (HR 2.51, p<0.001).
• Increased mortality risk observed up to 365 days post-hypoglycemia, maintained after baseline adjustments.

Conclusions:

• Severe hypoglycemia is associated with increased all-cause mortality in type 2 diabetes patients.
• Patients experiencing severe hypoglycemia face a greater short-term risk of death.
• The study indicates severe hypoglycemia is a risk marker for mortality, but causality remains undetermined.