skip to Main Content

Tenapanor (IBSRELA) for Treatment of IBS-C: Effective Over 26 Weeks

Philip Schoenfeld, MD, MSEd, MSc (Epi)

Chief (Emeritus)-Gastroenterology Section, John D. Dingell VA Medical Center, Detroit, MI

This article reviews Chey WD, Lembo A, Yang Y, Rosenbaum DP. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome with Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2). Am J Gastroenterol 2021; 116: 1294-1303.

Access the Review in Evidence-Based GI

Access the Article in The American Journal of Gastroenterology

Listen to the Audio Summary




Tenapanor is a first-in-class, minimally absorbed, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3. This phase 3 trial assessed the long-term efficacy and safety of tenapanor 50 mg b.i.d. for the treatment of patients with irritable bowel syndrome with constipation (IBSC).


In this randomized double-blind study ( identifier: NCT02686138), patients with IBSC received tenapanor 50 mg b.i.d. or placebo b.i.d. for 26 weeks. The primary endpoint was the proportion of patients who had a reduction of ≥30.0% in average weekly worst abdominal pain and an increase of ≥1 weekly complete spontaneous bowel movement from baseline, both in the same week, for ≥6 of the first 12 treatment weeks (6/12-week combined responder).


Of the 620 randomized patients with IBSC, 593 (95.6%) were included in the intention-to-treat analysis set (tenapanor: n = 293; placebo: n = 300) and 481 patients (77.6%) completed the 26-week treatment period. In the intention-to-treat analysis set (mean age: 45.4 years; 82.1% women), a significantly greater proportion of patients treated with tenapanor were 6/12-week combined responders than those treated with placebo (36.5% vs 23.7%; P < 0.001). Abdominal symptoms and global symptoms of IBS were significantly improved with tenapanor compared with placebo. Diarrhea, the most common adverse event, was typically transient and mild to moderate in severity. Diarrhea led to study drug discontinuation for 19 (6.5%) and 2 patients (0.7%) receiving tenapanor and placebo, respectively.


Tenapanor 50 mg b.i.d. improved IBSC symptoms over 26 weeks and was generally well tolerated, offering a potential new long-term treatment option for patients with IBSC (see Visual abstract, Supplementary Digital Content 1,

Access the Article in The American Journal of Gastroenterology

Back To Top