Devoting attention to glucose variability and hypoglycaemia in type 2 diabetes.

Area of Science:

• Cardiovascular medicine
• Endocrinology
• Diabetes research

Background:

• The Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine (DEVOTE) showed insulin degludec was non-inferior to insulin glargine for cardiovascular events and mortality, with lower severe hypoglycemia rates.
• Observational analyses from DEVOTE data (DEVOTE 2 and DEVOTE 3) investigated the impact of glycemic variability and severe hypoglycemia on outcomes in high-risk type 2 diabetes patients.

Purpose of the Study:

• To analyze the association between day-to-day fasting glycemic variability and major adverse cardiovascular events (MACE), severe hypoglycemia, and mortality.
• To assess the risk of MACE and mortality in patients who experienced severe hypoglycemia compared to those who did not.

Main Methods:

• DEVOTE 2: Compared outcomes based on high vs. lower day-to-day fasting glycemic variability in insulin-treated type 2 diabetes patients.
• DEVOTE 3: Compared MACE and mortality risks in patients with and without severe hypoglycemia events.

Main Results:

• Higher glycemic variability was associated with similar MACE risk but increased risk of severe hypoglycemia and all-cause mortality.
• Severe hypoglycemia was linked to similar MACE risk but more than double the risk of subsequent total and cardiovascular disease mortality.

Conclusions:

• While DEVOTE 2 and DEVOTE 3 highlight mortality risks associated with glycemic variability and severe hypoglycemia, causal relationships cannot be confirmed due to observational data and trial limitations.
• Preventing severe hypoglycemia is a clinical priority; future trials are needed to determine if targeting glycemic variability benefits high-risk type 2 diabetes patients by reducing cardiovascular events and mortality.