Hypoglycemia increases the risk of cardiovascular events in patients with type 2 diabetes

This study examined the risk of serious cardiovascular events, such as heart attack and stroke, in patients with type 2 diabetes (T2D). It found that hypoglycemia (low blood-glucose) was associated with an increased risk of these events.

Patients with T2D are at a higher risk of cardiovascular events. Previous studies have examined whether intensive treatment of high blood glucose levels could decrease the risk of these events. Hypoglycemia can occur as a result of intensive treatment of T2D. These previous studies suggested that hypoglycemia might increase the risk of cardiovascular events.  

Dipeptidyl peptidase-4 (DPP-4) inhibitors are treatments that reduce blood glucose levels, increase insulin secretion, and reduce the speed at which food empties from the stomach. In a prior study, the DPP-4 inhibitor alogliptin (Nesina) was not found to increase the rate of cardiovascular events. It is not clear, however, whether HbA1c (average blood glucose over 3 months) affected this result.

The current study examined whether HbA1c affected the rate of cardiovascular events in patients with T2D. 5380 patients were recruited for this study. All had experienced a recent acute coronary syndrome (situation where blood supply to the heart muscle is suddenly blocked). Half of the patients were treated with alogliptin in addition to their normal treatment. The other half received a placebo (substance with no active effect). Both groups were followed up after 1, 3, 6, 9, and 12 months, and then every 4 months.

The group treated with alogliptin achieved lower HbA1c  than the placebo group. HbA1c at the start of the study and after 1 month had no impact on the risk of serious cardiovascular events. Hypoglycemia was not more likely in the group treated with alogliptin.

Patients who had had a serious incident of hypoglycemia were 2.42 times more likely to have a major cardiovascular event. Patients who had had any type of hypoglycemia were 38% more likely to have a major cardiovascular event. When examining only major cardiovascular events that occurred after a hypoglycemia incident, the link was not significant. Patients with serious hypoglycemia were all being treated with insulin and sulphonylureas (a type of drug that increases the release of insulin in the body).

This study concluded that baseline HbA1c or HbA1c levels after 1 month of treatment were not associated with cardiovascular events. Alogliptin improved glycemic control without increasing hypoglycemia. The authors suggested that hypoglycemia was associated with an increased risk of major cardiovascular events. 

No significant relationship between hypoglycemia and future cardiovascular events was found. It is therefore possible that a third, unexamined, factor is responsible for the association.

Discuss the risk of cardiovascular events with your physician if you are undergoing treatment for T2D.