Efficacy and safety of tenapanor vs placebo in treating CKD patients on dialysis and with hyperphosphatemia: a systematic review and meta-analysis of 2251 patients.

Background: Hyperphosphatemia is common in chronic kidney disease (CKD) patients, especially patients on hemodialysis. Tenapanor is a novel drug with fewer side effects and high compliance compared to traditional phosphate binders. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of tenapanor.

Methods: A comprehensive search was conducted on PubMed, Scopus, Web of Science, and Cochrane Library, from inception to June 25, 2024. Nine randomized controlled trials (RCTs) and three single-arm studies comparing tenapanor to placebo were included. By adopting a random-effect empirical Bayes model, STATA and RevMan were used to pool dichotomous and continuous data. The primary outcome assessed was serum phosphate. Secondary outcomes included intact parathyroid hormone (iPTH), serum calcium, potassium, and sodium, bowel movement frequency, stool consistency using BSFS score and safety outcomes.

Results: Twelve studies with a total of 2,251 patients were included. Tenapanor was superior to placebo in reducing phosphate at all assessed end points, week 1 (MD = -1.28 mg/dL, P < 0.001), week 2 (MD = -1.07 mg/dL, P < 0.001), week 3 (MD = -1.22 mg/dL, P < 0.001), and week 4 (MD = -0.91 mg/dL, P < 0.001). In addition, iPTH was almost statistically significantly lower in the tenapanor group (MD = -36.53 ng/L, P = 0.07). Moreover, it led to a statistically significant reduction in sodium level (MD = -0.7 mmol/L, P = 0.0003). On the contrary, tenapanor had no statistically significant effect on calcium or potassium levels. Bowel movement frequency and stool consistency were significantly higher in the tenapanor group at all assessed end points. Regarding safety analysis, diarrhea and nausea were statistically significantly higher in the tenapanor group, (RR = 3.71, P < 0.001) and (RR = 1.97, P < 0.001), respectively. There were no significant differences in other adverse events.

Conclusion: Based on our meta-analysis, tenapanor can effectively reduce serum phosphate, iPTH, and sodium. Additionally, it improves bowel movement frequency and stool consistency. However, it is associated with a higher risk of GIT symptoms that should be considered and managed during treatment. We recommend conducting further RCTs to perform head-to-head comparisons against other active comparators such as phosphate binders.