Can combined therapy with sodium-glucose co-transporter 2 inhibitors and sulfonylureas affect the risk of hypoglycemia in patients with type 2 diabetes?

This review assessed the risk of hypoglycemia (dangerously low blood glucose) with the addition of sodium-glucose co-transporter 2 (SGLT-2) inhibitors to sulfonylureas in patients with type 2 diabetes (T2D). The authors concluded that this combination was associated with an increased risk of hypoglycemia.

T2D affects the regulation and use of glucose, resulting in increased blood glucose (hyperglycemia). Glucose-lowering oral drugs such as sulfonylureas are commonly used in patients with T2D. However, many glucose-lowering medications increase the risk of abnormally low blood glucose (hypoglycemia).  Hypoglycemia has been linked to an increased risk of heart disease, impaired daily activities, and mortality.

SGLT-2 inhibitors represent a newer class of oral glucose-lowering drugs. They reduce blood glucose levels by increasing the amount of glucose that is passed in the urine. On their own, the risk of hypoglycemia is similar to other oral anti-diabetic drugs. However, some studies indicate that hypoglycemia is significantly increased when SGLT-2 inhibitors are administered with sulfonylureas such as glimepiride (Amaryl). However, other studies do not support these findings. There is a need to assess the risk of hypoglycemia due to the use of SGLT-2 inhibitors with sulfonylureas in patients with T2D.  

This review analyzed 12 studies with a total of 3761 patients with T2D. 2529 patients received SGLT-2 inhibitors with sulfonylureas. 1232 patients received a placebo with sulfonylureas. The risk of hypoglycemia was evaluated.

There was a 67% higher risk of hypoglycemia when an SGLT-2 inhibitor was given with sulfonylureas to patients with T2D, compared to placebo and sulfonylureas.

The study showed that the combination of SGLT-2 inhibitors and sulfonylureas increases the risk of hypoglycemia in patients with T2D.  

This review included studies with varied definitions of hypoglycemia. Many different types of SGLT-2 inhibitors and sulfonylurea were included in these studies.