Chronic Constipation
Persistent difficulty with bowel movements lasting at least 3 months. Linaclotide and plecanatide are approved peptide treatments that activate guanylate cyclase-C receptors on intestinal epithelial cells, increasing fluid secretion and accelerating intestinal transit.
Technical Context
Defined as: <3 spontaneous bowel movements per week for ≥3 months with additional symptoms (straining, hard stools, incomplete evacuation, sensation of blockage). Linaclotide (14 amino acids) and plecanatide (16 amino acids) are structurally related to uroguanylin (an endogenous GC-C agonist). Their local mechanism of action in the GI lumen (no clinically significant systemic absorption — peptides are degraded in the intestine) provides a favourable safety profile. Unlike osmotic or stimulant laxatives, GC-C agonists address the underlying secretory and sensory dysfunction rather than merely promoting evacuation. Linaclotide Phase III trials showed significant improvement in complete spontaneous bowel movements (CSBM), straining, abdominal pain, and global symptom relief vs placebo.