To evaluate the efficacy of chiglitazar, a novel pan-PPAR agonist, on metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with type 2 diabetes (T2D) in a real-world clinical setting.

This prospective cohort study included T2D patients with MASLD who received either chiglitazar or other glucose-lowering medications over a 24-week period. To minimize selection bias, 1:1 propensity score matching (PSM) was implemented. The primary outcomes were changes in controlled attenuation parameter (CAP, measuring hepatic steatosis) and liver stiffness measurement (LSM, assessing fibrosis). Secondary outcomes included glycemic parameters and liver enzymes.

A total of 235 T2D patients were enrolled (40 chiglitazar users, 195 non-chiglitazar users), and 31 matched pairs were derived after 1:1 PSM. The adjusted mean reduction in CAP from baseline to 24 weeks was significantly greater in the chiglitazar group (-28.38 dB/m [95 % CI:36.11;-20.65]) compared to the non-chiglitazar group (-16.74 dB/m [-24.47;-9.01]), with a between-group difference of -11.64 dB/m (-22.38;-0.90, P = 0.038). LSM changes were similar between groups (difference in LS mean:0.11 [-1.04;0.82], P = 0.813). Subgroup analyses indicated that the beneficial effect of chiglitazar was consistent across variables such as sex, age, body mass index, and concomitant use of SGLT-2 inhibitors or GLP-1 receptor agonists (all P for interaction > 0.05).

Chiglitazar administration is associated with a significant reduction in CAP values in T2D patients with MASLD, suggesting its potential as a dual therapeutic approach for both conditions.