Pharmacologic Differences of Sulfonylureas and the Risk of Adverse Cardiovascular and Hypoglycemic Events

Diabetes Care. 2017 Nov;40(11):1506-1513. doi: 10.2337/dc17-0595. Epub 2017 Sep 1.

Abstract

Objective: Sulfonylureas have been associated with an increased risk of cardiovascular adverse events and hypoglycemia, but it is unclear if these risks vary with different agents. We assessed whether the risks of acute myocardial infarction, ischemic stroke, cardiovascular death, all-cause mortality, and severe hypoglycemia differ between sulfonylureas grouped according to pancreas specificity and duration of action.

Research design and methods: Using the U.K. Clinical Practice Research Datalink, linked with the Hospital Episodes Statistics and the Office for National Statistics databases, we conducted a cohort study among patients with type 2 diabetes initiating monotherapy with sulfonylureas between 1998 and 2013. Adjusted hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, comparing use of pancreas-nonspecific, long-acting sulfonylureas (glyburide/glimepiride) to pancreas-specific, short-acting sulfonylureas (gliclazide/glipizide/tolbutamide).

Results: The cohort included 17,604 sulfonylurea initiators (mean [SD] follow-up 1.2 [1.5] years). Compared with specific, short-acting sulfonylureas (15,741 initiators), nonspecific, long-acting sulfonylureas (1,863 initiators) were not associated with an increased risk of acute myocardial infarction (HR 0.86; CI 0.55-1.34), ischemic stroke (HR 0.92; CI 0.59-1.45), cardiovascular death (HR 1.01; CI 0.72-1.40), or all-cause mortality (HR 0.81; CI 0.66-1.003), but with an increased risk of severe hypoglycemia (HR 2.83; CI 1.64-4.88).

Conclusions: The nonspecific, long-acting sulfonylureas glyburide and glimepiride do not have an increased risk of cardiovascular adverse events compared with the specific, short-acting sulfonylureas gliclazide, glipizide, and tolbutamide. However, nonspecific, long-acting sulfonylureas glyburide and glimepiride have an increased risk of severe hypoglycemia.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • Cardiovascular Diseases / mortality*
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / drug therapy
  • Female
  • Follow-Up Studies
  • Gliclazide / administration & dosage
  • Gliclazide / adverse effects
  • Glipizide / administration & dosage
  • Glipizide / adverse effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / mortality*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Incidence
  • Male
  • Middle Aged
  • Myocardial Infarction / mortality
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Proportional Hazards Models
  • Risk Factors
  • Stroke / mortality
  • Sulfonylurea Compounds / administration & dosage*
  • Sulfonylurea Compounds / adverse effects*
  • Tolbutamide / administration & dosage
  • Tolbutamide / adverse effects
  • United Kingdom / epidemiology

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Tolbutamide
  • Gliclazide
  • Glipizide

Grant support