Effect of dietary counseling and dietary fiber on tolerability during weight management with EMP16 and conventional orlistat: a single-blind randomized pilot trial.

The aim of this trial was to assess whether dietary counseling together with supplemental fiber improves gastrointestinal (GI) tolerability during dose escalation with controlled-release orlistat-acarbose (EMP16) in adults who had reported prior GI side effects. In this randomized, single-blind, phase 2 pilot trial, adults with obesity (BMI ≥ 30 kg/m² or ≥ 27 kg/m² with risk factors) and prior GI problems to conventional orlistat or EMP16 were randomized 1:2 to EMP16 plus psyllium-based fiber or conventional orlistat plus maltodextrin placebo for 39 days, both with diet counseling. The primary endpoint was the composite gastrointestinal tolerability events (GITE) area-under-the-curve (AUC) score (diarrhea, oily spotting, flatulence with discharge, fecal incontinence) from daily electronic diaries. Additional endpoints included investigator-assessed GI adverse events, anthropometry, and cardiometabolic markers. Thirty-six participants completed treatment. GI event rates were much lower than expected in both arms, and GITE AUC differences were not statistically significant. Total events and time to first GI event favored EMP16 plus fiber. Greater relative weight loss occurred with EMP16 plus fiber vs. conventional orlistat plus placebo (p = 0.026), with similar ~ 10% LDL-cholesterol reductions. Dietary counseling during treatment with EMP16 or conventional orlistat may mitigate GI side effects in adults with prior GI side effects and co‑administration of fiber might further enhance tolerability and efficacy.