Exenatide: first-in-class incretin mimetic for the treatment of Type 2 diabetes mellitus - PubMed (original) (raw)
Exenatide: first-in-class incretin mimetic for the treatment of Type 2 diabetes mellitus
Curtis Triplitt et al. Expert Rev Endocrinol Metab. 2006 May.
Abstract
Exenatide is the first-in-class incretin mimetic for the treatment of Type 2 diabetes mellitus. Mechanistically, it mimics several of the glucoregulatory effects of glucagon-like peptide-1 including: 1) glucose-dependent insulin secretion via the glucose-dependent glucagon-like peptide-1 pancreatic receptor; 2) suppression of elevated plasma glucagon levels; 3) reduction in the rate of appearance of glucose into the systemic circulation by normalizing the accelerated rate of gastric emptying often present in Type 2 diabetes mellitus; 4) reduction of food intake, which in turn promotes weight loss; 5) stimulation of the glucagon-like peptide-1 receptor. A1C reductions of approximately 1% can be expected with a baseline A1C of 8.0-8.5%. Exenatide significantly reduces postprandial glucose levels, while having only a modest effect on the fasting plasma glucose. Hypoglycemic risk is no different to placebo when combined with metformin or a thiazolidinediones, but is higher when combined with a sulfonylurea, possibly requiring reduction in the sulfonylurea dose. Exenatide may cause gastrointestinal side effects upon initiation, which usually lessen over time. Gastrointestinal side effects can be reduced by starting exenatide 5 µg subcutaneously twice daily before meals; if tolerated, titration to 10 µg twice daily before meals at 1 month may further improve glycemia and weight loss.
Keywords: diabetes; exenatide; glucagon-like peptide-1; incretin mimetics.
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