Sulfonylurea

Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture. They are antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas. A number of sulfonylureas are also used as herbicides, because they can interfere with plant biosynthesis of certain amino acids. Sulfonylureas are also used experimentally to inhibit interleukin 1 beta release from the NALP3 (or NLRP3) inflammasome.Sulfonylurea group highlighted in (red)General formula of a sulfonylurea, showing the sulfonylurea backbone itself in red and the side chains that distinguish each compound in blue.Chlorpropamide (1st generation)Tolazamide (1st generation)Gliclazide (2nd generation)Glimepiride (2nd generation) Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture. They are antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas. A number of sulfonylureas are also used as herbicides, because they can interfere with plant biosynthesis of certain amino acids. Sulfonylureas are also used experimentally to inhibit interleukin 1 beta release from the NALP3 (or NLRP3) inflammasome. Sulfonylureas are used primarily for the treatment of diabetes mellitus type 2. Sulfonylureas are ineffective where there is absolute deficiency of insulin production such as in type 1 diabetes or post-pancreatectomy. Sulfonylureas can be used to treat some types of neonatal diabetes. While historically people with hyperglycemia and low blood insulin levels were diagnosed with type I diabetes by default, it has been found that patients who receive this diagnosis before 6 months of age are often, in fact, candidates for receiving sulfonylureas rather than insulin throughout life. While prior sulfonylureas were associated with worse outcomes, newer agents do not appear to increase the risk of death, heart attacks, or strokes. Sulfonylureas, as opposed to metformin, the thiazolidinediones, exenatide, pramlintide and other newer treatment agents may induce hypoglycemia as a result of excesses in insulin production and release. This typically occurs if the dose is too high, and the patient is fasting. Some people attempt to change eating habits to prevent this, however it can be counter productive. Like insulin, sulfonylureas can induce weight gain, mainly as a result of their effect to increase insulin levels and thus utilization of glucose and other metabolic fuels. Other side-effects are: gastrointestinal upset, headache and hypersensitivity reactions. The safety of sulfonylurea therapy in pregnancy is unestablished. Prolonged hypoglycemia (4 to 10 days) has been reported in children borne to mothers taking sulfonylureas at the time of delivery. Impairment of liver or kidney function increase the risk of hypoglycemia, and are contraindications. As other anti-diabetic drugs cannot be used either under these circumstances, insulin therapy is typically recommended during pregnancy and in hepatic and renal failure, although some of the newer agents offer potentially better options. A 2014 Cochrane review found tentative evidence that people treated with sulfonylureas have fewer non-fatal cardiovascular events than those treated with metformin (RR 0.67, 95% CI 0.48 to 0.93) but a higher risk of severe hypoglycemia (RR 5.64, 95% CI 1.22 to 26.00). There was not enough data available to determine the relative risk of mortality or of cardiovascular mortality. An earlier review by the same group found a statistically significant increase in the risk of cardiovascular death for first generation sulfonylureas relative to placebo (RR 2.63, 95% CI 1.32 to 5.22; P = 0.006) but there was not enough data to determine the relative risk of first generation sulfonylureas relative to insulin (RR 1.36, 95% CI 0.68 to 2.71; P = 0.39). Likewise it was not possible to determine the relative mortality risk of second generation sulfonylureas relative to metformin (RR 0.98, 95% CI 0.61 to 1.58; P = 0.68), insulin (RR 0.96, 95% CI 0.79 to 1.18; P = 0.72), or placebo. The FDA requires sulfonylureas to carry a label warning regarding increased risk of cardiovascular death. Second-generation sulfonylureas have increased potency by weight, compared to first-generation sulfonylureas. Similarly, ACCORD (Action to Control Cardiovascular Risk in Diabetes) and the VADT (Veterans Affairs Diabetes Trial) studies showed no reduction in heart attack or death in patients assigned to tight glucose control with various drugs.