Combination of insulin therapy and sulfonylureas: a literature review

Article Abstract:

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by hyperglycemia, or elevated blood glucose levels. People with NIDDM are at a much higher risk for developing vascular disease, kidney disease and eye problems. Most patients are treated with sulfonylurea agents. These drugs maintain good glycemic (blood sugar) control in most patients with NIDDM; they increase insulin secretion and may increase sensitivity to insulin as well. A large number of NIDDM patients either do not respond to therapy with these drugs or drug responsiveness diminishes over time. Insulin therapy is also used to treat NIDDM, but may cause adverse side effects and does not always lead to good glycemic control. Consequently, insulin is not usually the preferred treatment for NIDDM. Combining the two treatments has been suggested for certain patients with NIDDM. Recently, a number of studies have evaluated the effectiveness and safety of combined hypoglycemic (blood glucose-lowering) therapy. Results have been promising, with patients obtaining good glycemic control and requiring relatively low doses of insulin. The reduction in insulin dosages in combined therapy appears to be due to increased insulin secretion (by the pancreatic beta cells) induced by the sulfonylurea agents. Combined therapy resulted in more cases of hypoglycemia (low blood sugar), but the cases were mild. Weight gains were also noted. Combined therapy can result in a 30 to 50 percent increase in treatment cost. Studies have examined using combined therapy to treat insulin-dependent diabetes. Most patients have shown no improvement over insulin therapy alone. This would indicate that sulfonylurea agents mainly act by stimulating insulin secretion by the pancreas; such stimulation is useless in insulin-dependent diabetics. In conclusion, combined therapy appears useful in treating certain cases of NIDDM, but not insulin-dependent diabetes. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cases, Hypoglycemic agents, Type 1 diabetes, Insulin, Drug synergism, editorial

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Effects of sulfonylureas on adipocyte and skeletal muscle insulin action in patients with non-insulin-dependent diabetes mellitus

Article Abstract:

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by abnormally high fasting blood glucose levels. It appears to be caused by insulin resistance in the liver, poor glucose uptake by the tissues, and abnormal pancreatic beta cell response to glucose levels, which results in reduced insulin secretion. (The pancreatic beta cells secrete the hormones insulin and glucagon.) Appropriate drug therapy for NIDDM should involve improving one or more of these abnormalities. Sulfonylurea agents appear to be effective in treating NIDDM. Recent studies have shown that they enhance the uptake of glucose in tissues that require insulin. This study examined the effects of the sulfonylurea glibenclamide on the action of insulin and the uptake of glucose in adipose (fat) cells. The drug was given to eight obese NIDDM patients who had not responded to diet therapy. Blood glucose levels were measured and adipose tissue samples were examined before and three months after therapy was initiated. Results showed that glycemic control (of blood glucose levels) was improved with glibenclamide treatment. Blood glucose concentrations averaged 10.8 millimoles per liter (mmol/L) before and 7.0 mmol/L after therapy. Insulin concentrations increased from an average of 40 mU/L before to 71 mU/L after therapy. Glibenclamide did not seem to enhance insulin binding to receptors on the adipose cells. Insulin-stimulated glucose transport and lipogenesis (production of fat) in the cells was shown to increase with drug therapy. These results confirm that glibenclamide improves glycemic control in NIDDM patients, and that the effects are at least partially due to increased glucose disposal by adipose tissues. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Muscle cells, Fat cells, Adipocytes

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Effects of the sulfonylureas on muscle glucose homeostasis

Article Abstract:

Sulfonylureas are agents used to treat non-insulin-dependent diabetes mellitus (NIDDM), a disorder of glucose metabolism, which develops mainly in obese adults. NIDDM is characterized by hyperglycemia, or increased blood levels of glucose, and glycosuria, the excretion of glucose in the urine, which result from the decreased utilization of glucose by tissues. In NIDDM, the cells are less responsive to the actions of insulin, a hormone which regulates the consumption of glucose by cells for the production of energy. Insulin is produced by the beta cells of the pancreas and normally released in response to increased blood levels of glucose. Sulfonylureas such as glyburide increase the release of insulin from the pancreas and the responsiveness of the tissues to insulin. The skeletal muscle is an important site of glucose consumption and may influence the balance of glucose in the body. The effects of glyburide on glucose uptake by skeletal muscle were assessed. Glyburide appears to enhance the insulin-activated uptake of glucose by skeletal muscle, but does not appear to alter glucose balance in the absence of insulin. The mechanism by which sulfonylureas enhance insulin-activated glucose uptake by skeletal muscle is not known, but may involve effects on the production and numbers of glucose transport proteins, which mediate the uptake of glucose into skeletal muscle cells. Sulfonylureas may stimulate the production of glucose transport proteins, which may then be activated by insulin. This may explain why insulin is necessary for glyburide to exert its effect to increase glucose uptake by skeletal muscle. (Consumer Summary produced by Reliance Medical Information, Inc.)

Striated muscle, Glucose metabolism, Hypoglycemic sulphonylureas

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