Insulin secretagogues that enhance GLP-1 receptor signaling
They heighten glucose-dependent insulin secretion, reduce glucagon secretion, promote weight loss, slow gastric emptying, decrease appetite, and promote beta-cell regeneration. These are recommended for use as adjunctive therapy to improve glycemic control in patients who are taking metformin, or a combination of metformin and a sulfonylurea. They are:
- Glucagon-like peptide (GLP-1) analogues (also known as Incretins): These are discussed here.
- DPP-IV inhibitors (Gliptins) that inhibit degradation of native GLP-1 and thus enhance the incretin effect.
Incretins
GLP-1 receptor agonist (Incretins) enhance endogenous GLP-1 activity, amplify glucose-stimulated insulin secretion. They do not cause hypoglycemia. They do not promote weight gain, in fact, most patients experience modest weight loss and appetite suppression. Products available:
- Exenatide, a synthetic version of a peptide initially identified in the saliva of the Gila monster (exendin-4), is an analogue of GLP-1.
- Liraglutide, another GLP-1 receptor agonist, is almost identical to native GLP-1 except for an amino acid substitution and addition of a fatty acyl group. Liraglutide is a long acting GLP-1 receptor agonist. Cases of acute pancreatitis have been reported in use of liraglutide use. Brand: Victoza (Novo Nordisk)
- Semaglutide: Brand - Ozemic.
- Lixisenatide
- Albiglutide is a recombinant human serum albumin (HSA)-GLP-1 hybrid protein with half life of about a week.