Among sulfonylureas, no definitive advantages have been demonstrated for one compound compared with others in trials with hard endpoints. The potent long-acting sulfonylureas bear a higher risk of protracted hypoglycemias in elderly people who may miss meals, and in poorly controlled conditions. Shorter acting and less potent insulin releasers may be advantageous under these circumstances (16,28). Specific advantages have been proposed for gliclazide, due to its antioxidant actions, and glimepiride, due to its insulin sensitizing effects, both of which are of unknown significance (29,30).
Meglitinides have been compared with glibenclamide and glipizide with regard to effects on average glucose- and meal-related insulin secretion. Indeed, repaglinide and nateglinide caused a more rapid increase in meal-related insulin secretion compared with glibenclamide, and achieved a more potent lowering of postprandial increases in glucose. Studies with nateglinide performed in patients with a fasting glucose slightly above 200 mg/ dL also showed that nateglinide was less potent in lowering fasting plasma glucose. Used as a single agent, the therapeutic effect is relatively small and HbA1c was lowered by 0.6%. Thus, the drug appears most suitable for use in early diabetes. With more pronounced elevations of fasting glucose, combination with metformin was effective. This is, however, true for all combinations of sulfonylureas with metformin (see below). The faster acting meglitinides may achieve better postprandial control of blood glucose in combination with metformin or insulin sensitizers. It is unproven whether this difference of postprandial glucose results in advantages for the patient with regard to the risk of macrovascular disease.
Increases in postprandial glucose were shown to be associated with elevated risk of cardiovascular disease in impaired glucose tolerance (Lancet Decode 1999). This was not shown as well among patients with manifest type 2 diabetes. The extrapolation of studies in impaired glucose tolerance suggest that near-normal control of glucose, both fasting and postprandial, should decrease the cardiovascular risk associated with type 2 diabetes back to the normal range. Although this is plausible, and is expressed in the current treatment guidelines, it has not yet been proven in prospective trials. Such trials would have to overcome the difficulty that it is presently much harder to lower blood glucose into the normal range than to lower blood pressure or elevated cholesterol levels. However, the impact of clinical studies demonstrating a substantial advantage of normalizing—and not just lowering—blood glucose would be enormous and would change current treatment practices.
A reduction of postprandial glucose levels, however, is most likely to be successful in a setting of normalized fasting glucose levels i.e., 80 to 120 mg/dL. Advantages of better control of postprandial glucose are of unknown relevance with permanently elevated fasting glucose levels.
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Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...