Gastrointestinal actions of glucagon-like peptide-1-based therapies
Glycaemic control beyond the pancreas
Diabetes, Obesity and Metabolism , Volume 18 - Issue 3 p. 224- 235
The gastrointestinal hormone glucagon-like peptide-1 (GLP-1) lowers postprandial glucose concentrations by regulating pancreatic islet-cell function, with stimulation of glucose-dependent insulin and suppression of glucagon secretion. In addition to endocrine pancreatic effects, mounting evidence suggests that several gastrointestinal actions of GLP-1 are at least as important for glucose-lowering. GLP-1 reduces gastric emptying rate and small bowel motility, thereby delaying glucose absorption and decreasing postprandial glucose excursions. Furthermore, it has been suggested that GLP-1 directly stimulates hepatic glucose uptake, and suppresses hepatic glucose production, thereby adding to reduction of fasting and postprandial glucose levels. GLP-1 receptor agonists, which mimic the effects of GLP-1, have been developed for the treatment of type 2 diabetes. Based on their pharmacokinetic profile, GLP-1 receptor agonists can be broadly categorized as short- or long-acting, with each having unique islet-cell and gastrointestinal effects that lower glucose levels. Short-acting agonists predominantly lower postprandial glucose excursions, by inhibiting gastric emptying and intestinal glucose uptake, with little effect on insulin secretion. By contrast, long-acting agonists mainly reduce fasting glucose levels, predominantly by increased insulin and reduced glucagon secretion, with potential additional direct inhibitory effects on hepatic glucose production. Understanding these pharmacokinetic and pharmacodynamic differences may allow personalized antihyperglycaemic therapy in type 2 diabetes. In addition, it may provide the rationale to explore treatment in patients with no or little residual β-cell function.
|Antihyperglycaemic drugs, Extrapancreatic mechanisms, GLP-1 receptor agonists|
|Diabetes, Obesity and Metabolism|
|Organisation||Department of Gastroenterology & Hepatology|
Smits, M.M, Tonneijck, L, Muskiet, M.H.A, Kramer, M.H.H, Cahen, D.L, & van Raalte, D.H. (2016). Gastrointestinal actions of glucagon-like peptide-1-based therapies. Diabetes, Obesity and Metabolism (Vol. 18, pp. 224–235). doi:10.1111/dom.12593