Evaluating Long-Term Persistence of FDA-Approved Secretagogues for Chronic Idiopathic Constipation: A Real-World Analysis

Presenter: Hamilton B.

This retrospective cohort study evaluated real-world treatment persistence among adults with chronic idiopathic constipation (CIC) initiated on the secretagogues linaclotide, lubiprostone, or plecanatide within a large academic health system. Adults prescribed these agents between January 2019 and December 2024 were included, and treatment duration was defined from the earliest prescription date to the last documented refill.

A total of 1,510 patients were included, comprising 1,153 treated with linaclotide, 201 with lubiprostone, and 156 with plecanatide. Baseline differences were observed across treatment groups prior to matching; however, PSM substantially improved covariate balance, with most standardized mean differences approaching zero following adjustment. Kaplan–Meier analysis demonstrated significant differences in treatment persistence across agents (log-rank p<0.001). Linaclotide showed the greatest treatment persistence, plecanatide demonstrated intermediate persistence, and lubiprostone had the shortest persistence duration.

In Cox proportional hazards analyses, both lubiprostone and plecanatide were associated with significantly higher risks of treatment discontinuation compared with linaclotide. No significant associations were identified between persistence and demographic factors, psychiatric comorbidities, BMI, or laboratory parameters.

Overall, these findings provide real-world evidence supporting greater treatment persistence with linaclotide compared with lubiprostone and plecanatide in patients with CIC.

Linaclotide Efficacy in Adults with Severe Chronic Idiopathic Constipation (CIC): A Post-hoc Pooled Analysis of Phase 3 Studies

Presenter: Lembo A.

This post hoc pooled analysis evaluated the efficacy of linaclotide (LIN) in adults with severe chronic idiopathic constipation (CIC), focusing on symptom improvements beyond the conventional FDA-responder endpoint. Data were pooled from four Phase 3 randomized, placebo-controlled studies assessing LIN 72 µg, LIN 145 µg, and placebo over 12 weeks. Severe CIC was defined as the absence of complete spontaneous bowel movements (CSBMs) during the 2-week baseline period. Outcomes included changes in spontaneous bowel movements (SBMs), CSBMs, stool consistency, straining, constipation severity, and abdominal symptoms including pain, bloating, and discomfort.

Among 2,400 enrolled patients, 1,773 (74%) met criteria for severe CIC at baseline. Over the 12-week treatment period, patients receiving LIN achieved mean weekly CSBM frequencies of 1.6–1.8 and SBM frequencies of 3.7–4.4. Both LIN doses demonstrated significantly greater improvements in weekly SBM and CSBM frequency compared with placebo (nominal p<0.001 for both doses), along with improved stool consistency.

Across most evaluated symptom domains, a greater proportion of patients treated with LIN experienced clinically meaningful symptom improvement compared with placebo. Improvements were observed in straining, constipation severity, bloating, and abdominal discomfort, while abdominal pain improvement was less evident in the LIN 72 µg group. Symptom improvement rates generally appeared greatest with LIN 145 µg. Sensitivity analyses in patients with severe baseline symptoms supported these findings.

Overall, LIN 72 µg and 145 µg improved bowel movement frequency, stool consistency, and multiple constipation-related symptoms in patients with severe CIC, highlighting its benefit in addressing both bowel function and overall symptom burden in this difficult-to-treat population.

DDW 2026, May 2-5, Chicago, IL