Plecanatide: a new guanylate cyclase agonist for the treatment of chronic idiopathic constipation

Chronic constipation affects millions of Americans, consumes significant healthcare resources, and significantly affects quality of life (QOL). Recently, several new treatment options have become available for the treatment of constipation, including intestinal secretagogues such as lubiprotone, and linaclotide, prokinetics such as prucalopride, and bile acid transporter antagonists. Plecanatide is the newest of the secretagogue class of compounds that has been approved by the US Food and Drug Administration for the treatment of adults with chronic idiopathic constipation (CIC) in the USA. It is a guanylate cyclase agonist, and a 16 amino acid synthetic peptide that is a structural analog of human uroguanylin. Two large randomized, double-blind, placebo-controlled studies assessed the efficacy and safety of plecanatide in CIC patients (Rome III). Both doses of plecanatide, 3 mg and 6 mg resulted in a significantly greater percentage of patients who were durable overall complete spontaneous bowel movement (CSBM) responders (primary endpoint) compared with those who received placebo (plecanatide 3 mg, 21.0%; plecanatide 6 mg, 19.5%; placebo, 10.2%; p < 0.001 for each drug dose versus placebo). Plecanatide treatment also significantly reduced the severity of other CIC symptoms (straining effort, stool consistency, bloating). Also, plecanatide-treated patients reported high levels of satisfaction and improved QOL and desire to continue treatment. The rate of treatment-emergent adverse events with plecanatide was low, including rates of diarrhea (5%). Plecanatide is a luminally acting secretagogue that is efficacious and safe for the treatment of CIC. This article provides an overview of plecanatide in the management of adults with CIC.