From the Guidelines
Sulfonylureas are generally considered safe and cardiovascular neutral, with some benefits in microvascular outcomes, but are associated with an increased risk of hypoglycemia and weight gain.
Comparison of Sulfonylureas
- Sulfonylureas have been shown to be effective in lowering blood glucose by stimulating insulin secretion from pancreatic β-cells 1.
- They are inexpensive, widely available, and have high glucose-lowering efficacy, but are associated with weight gain and risk for hypoglycemia 1.
- The risk of hypoglycemia varies among different sulfonylureas, with glipizide, glimepiride, and gliclazide having a lower risk compared to other sulfonylureas 1.
- Newer-generation sulfonylureas, such as glimepiride, have been shown to be safe and cardiovascular neutral in large controlled clinical trials, including the CAROLINA randomized trial 1.
- Sulfonylureas have been linked to improved microvascular outcomes, specifically retinopathy and albuminuria, in the context of intensive glycemic control in the UKPDS study 1.
- However, sulfonylureas are known to have a lack of durable effect on glucose lowering, and down-titration of dose to reduce the risk of hypoglycemia results in higher HbA1c 1.
From the Research
Comparison of Sulfonylureas
- Sulfonylureas have been linked with increased cardiovascular disease risk, with a meta-analysis of 33 studies finding a significantly increased risk of cardiovascular death and composite cardiovascular events compared to other oral diabetes drugs 2.
- A population-based cohort study found that initiating treatment of type 2 diabetes with a sulfonylurea rather than metformin is associated with higher rates of ischemic stroke, cardiovascular death, and all-cause mortality 3.
- A systematic review comparing sulfonylureas and dipeptidyl peptidase-4 inhibitors as second-line therapies in type 2 diabetes found that sulfonylureas are considered better than DPP-4 inhibitors for treatment in patients with cardiovascular disease history and hypoglycemia, but may have a higher risk of hypoglycemic events 4.
- A cohort study assessing the risks of adverse cardiovascular and hypoglycemic events with different sulfonylureas found that nonspecific, long-acting sulfonylureas (glyburide and glimepiride) do not have an increased risk of cardiovascular adverse events compared to specific, short-acting sulfonylureas (gliclazide, glipizide, and tolbutamide), but have an increased risk of severe hypoglycemia 5.
- A systematic review and meta-analysis of head-to-head trials comparing sulfonylureas and low hypoglycaemic risk antidiabetic drugs found that sulfonylureas have higher odds for all-cause mortality, MACE, myocardial infarction, and hypoglycaemia compared to drugs with low hypoglycaemic potential, with important differences existing within the drug class 6.
Key Findings
- Sulfonylureas are associated with an increased risk of cardiovascular disease and hypoglycemic events compared to other oral diabetes drugs 2, 3, 6.
- The risk of adverse cardiovascular and hypoglycemic events may vary with different sulfonylureas, with nonspecific, long-acting sulfonylureas having an increased risk of severe hypoglycemia 5.
- Sulfonylureas may be considered better than DPP-4 inhibitors for treatment in patients with cardiovascular disease history and hypoglycemia, but may have a higher risk of hypoglycemic events 4.
- Important differences may exist within the sulfonylurea drug class, with glimepiride seeming to have the best safety profile 6.