Early Changes in Composite Insulin-Resistance Indices After Adjunctive Probiotic Treatment in Olanzapine-Treated Schizophrenia: A Longitudinal Secondary Analysis

Objective Olanzapine is effective for schizophrenia but commonly causes metabolic dysregulation. This study examined whether adjunctive probiotic treatment was associated with short-term changes in composite insulin-resistance-related indices during olanzapine therapy. Methods This longitudinal secondary analysis included 84 patients with schizophrenia receiving olanzapine: 40 received adjunctive Bifidobacterium tetravaccine live tablets and 44 received olanzapine alone. The triglyceride-glucose index (TyG), triglyceride-glucose–body mass index (TyG-BMI), metabolic score for insulin resistance (METS-IR), single-point insulin sensitivity estimator (SPISE), and triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) were assessed at baseline, Week 2, and Week 4. Baseline-adjusted linear mixed-effects models evaluated group × visit interactions and visit-specific contrasts. False discovery rate (FDR) correction and sensitivity analyses were applied. Results Significant group × visit interactions were observed for TyG-BMI ( P < 0.001; FDR <0.001) and SPISE ( P = 0.005; FDR = 0.012), but not for TyG, METS-IR, or TG/HDL-C. At Week 2, TyG-BMI was lower in the probiotic group (adjusted difference, −16.76; 95% CI, −23.78 to −9.74; P < 0.001; FDR <0.001), whereas SPISE was higher (adjusted difference, 0.54; 95% CI, 0.16 to 0.93; P = 0.006; FDR = 0.016). No index differed significantly between groups at Week 4. Conclusions Adjunctive probiotic treatment was associated with early favorable differences in TyG-BMI and SPISE, but these were not sustained at Week 4. TyG, METS-IR, and TG/HDL-C showed no significant primary-analysis effects. Larger, longer studies with direct insulin-based measurements are needed to determine reproducibility and clinical significance.