Sulfonylureas not supported as second-line treatment for type 2 diabetes
Risk for major adverse cardiovascular events and all-cause mortality was higher when a sulfonylurea was added to metformin compared to other typical second- or third-line therapy options in a recent Danish study.
Among second- and third-line treatments for type 2 diabetes, sulfonylurea added to metformin was associated with the greatest risk for adverse outcomes, according to a recent study.
Researchers in Denmark analyzed 20 years of data from a national registry to perform a time-to-event analysis of outcomes associated with different antihyperglycemic therapies. The primary end points were major adverse cardiovascular events (MACE), defined as nonfatal acute myocardial infarctions, nonfatal ischemic strokes, and cardiovascular deaths; severe hypoglycemia, defined as hypoglycemia as the primary cause of a hospitalization; and all-cause mortality. The goal of the study was to determine the efficacy and safety of dual and triple therapy for type 2 diabetes in a clinical setting. The results were published by Diabetes Care on April 1.
Overall, 66,807 patients with type 2 diabetes who were treated with metformin and different second- and third-line therapies were included in the study. Risk for MACE and all-cause mortality were highest in patients treated with metformin plus sulfonylurea, while risk for severe hypoglycemia was highest in patients treated with metformin plus basal insulin. Patients whose treatment regimen included a glucagon-like peptide-1 (GLP-1) receptor agonist had the lowest risk for MACE. Risk for all three end points, especially severe hypoglycemia, was lower in patients treated with metformin, a GLP-1 receptor agonist, or basal insulin than in patients treated with metformin plus basal insulin. A treatment regimen of metformin, a sodium-glucose cotransporter-2 inhibitor, and a GLP-1 receptor agonist was associated with the lowest risk for all three end points.
The study results could have been confounded by indication bias, and no data were available on HbA1c level, smoking status, body mass index, or cholesterol levels, among other limitations. The authors concluded that clinicians could consider adding a GLP-1 receptor agonist and reducing basal insulin in patients who are currently taking metformin plus basal insulin but are prone to hypoglycemia. They also concluded that based on their data, sulfonylurea is not supported as second-line treatment in patients with type 2 diabetes who are taking metformin.
“It is important to notice that these general recommendations are on a drug class level and should be combined with evidence on differences between individual compounds from other studies,” they wrote. “Furthermore, the choice of treatment is a multifactorial process in which many other factors, such as price, efficacy, other side effects, drug delivery technology, patient preferences, etc., should be considered.”