Gliclazide Combined With Metformin Associated With Lowest Risk of Hypoglycemia

New research suggests that gliclazide added to metformin in the treatment of type 2 diabetes (T2D) is associated with the lowest risk of hypoglycemia when compared with the newer generation sulphonylureas (SUs) (British Journal of Clinical Pharmacology).

Adding SUs, such as gliclazide, glipizide, glimepiride, and glibenclamide, to metformin remains a common strategy for treating T2D, but individual SUs differ and may confer different risks of abnormally low blood sugar.

Corresponding author Stig Ejdrup Andersen, MD, PhD, Roskilde University Hospital (Denmark), and his coauthor conducted a systematic review of randomized controlled trials lasting between 12 to 52 weeks and evaluated SUs added to inadequate metformin monotherapy (≥ 1000 mg/day) in those with T2D.

They found that in 16,260 patients from 13 trials of SUs and 14 trials of oral non-SU anti-hyperglycemic agents, the risk of hypoglycemia was lowest with gliclazide compared to glipizide (OR 0.22, CrI [credible interval] 0.05 to 0.96), glimepiride (OR 0.40, CrI 0.13 to 1.27), and glibenclamide (OR 0.21, CrI 0.03 to 1.48).

“Risk of hypoglycemia with the SU agents makes the newer and more expensive antidiabetics preferable when metformin monotherapy fails. However, our data indicate that the risk of hypoglycemia differs between the SU agents,” said Dr Andersen. “Thus, prescribing an SU with low risk of hypoglycemia might still be a rational and affordable alternative to many patients with type 2 diabetes.”

One major limitation of the review, authors note, is the varying definitions of hypoglycemia across studies. Nonetheless, they advise clinicians to consider the risk of agent-specific hypoglycemia when selecting an SU agent. —Amanda Del Signore