Traditional Chinese Medicine for Type 2 Diabetes with Metabolic-Associated Steatotic Liver Disease: Unified Effects and Design Thresholds

Youfang Liu¹bibi Wang¹liting Wang¹haozhe Xiong²Hua Zhang¹yang cheng^1*

• ¹Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
• ²Beijing University of Chinese Medicine, Beijing, China

Objective: To reorganize randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) for adults with type 2 diabetes mellitus (T2DM) and metabolic-associated steatotic liver disease (MASLD; including legacy NAFLD) into a clinical evidence–anchored knowledge graph (KG), and harmonize effect semantics ("Unified Effects") to support endpoint-and design-aware evidence navigation. Methods: We systematically reviewed RCTs (2015–2025). Effect direction and scale were unified using a prespecified rule (treatment effect [TE] >0 indicates improvement). Prespecified primary endpoints maximizing cross-trial comparability were alanine aminotransferase (ALT), triglycerides (TG), homeostatic model assessment of insulin resistance (HOMA-IR), and controlled attenuation parameter (CAP); aspartate aminotransferase (AST) was retained for robustness. Metabolic endpoints were synthesized at the 12-week timepoint, while imaging endpoints (CAP and liver stiffness measurement [LSM]) were synthesized within a prespecified 8–24-week window. Trials were stratified as Add-on versus Mixed, with primary efficacy inferences based on Add-on trials with balanced background Western medicine. Evidence was synthesized using REML-based random-effects meta-analysis (reporting prediction intervals) and weighted meta-regression. Risk of bias was assessed using RoB 2 and certainty of evidence using GRADE. Results: Ninety-five trials were included (n=8,813; follow-up 2–48 weeks; predominantly Add-on). The KG linked intervention categories (classic formulas, custom formulas, and Chinese patent medicines) to recurrent syndrome/symptom patterns; Salvia miltiorrhiza emerged as a central herb-layer hub. In Add-on trials, pooled effects for ALT, AST, HOMA-IR, and TG were directionally favorable, but heterogeneity was substantial and prediction intervals for biochemical endpoints were often wide and crossed the null. CAP showed a comparatively more reproducible short-term imaging signal than LSM. Meta-regression suggested hypothesis-generating design patterns in which estimate stability tended to improve with larger per-arm sample sizes (≈≥40–50) and longer follow-up (≈≥12–16 weeks). RoB 2 ratings were predominantly "some concerns," and GRADE certainty was commonly downgraded for inconsistency and/or imprecision. Conclusion: In adults with T2DM and MASLD, Add-on trials show directionally favorable pooled biochemical/metabolic changes after unified effect harmonization, but uncertainty remains substantial; CAP may be a more reproducible short-term imaging endpoint than LSM. Evidence-derived design patterns should be interpreted as hypothesis-generating rather than causal thresholds. Registration: PROSPERO CRD420251167450.