Abstract
INTRODUCTION: Type 2 diabetes (T2D) is a complex chronic metabolic disease characterized by insulin resistance, dyslipidemia, inflammation, and visceral fat accumulation, leading to complications, such as cardiovascular disease and kidney damage. Emerging metabolic regulators, including chiglitazar, semaglutide, and pioglitazone, have gained prominence in managing T2D and associated metabolic disorders. However, their relative efficacy and optimal clinical applications remain unclear. This study's objective was to compare the effects of chiglitazar, semaglutide, and pioglitazone on glycemic control, lipid metabolism, insulin resistance, inflammatory response, liver function, kidney function, and dawn phenomenon intensity in T2D participants, and to explore their relative efficacy and clinical value. METHODS: This retrospective study was conducted from October 2024 to November 2024 to compare the effects of chiglitazar, semaglutide, and pioglitazone in managing type 2 diabetes (T2D) and associated metabolic disorders.This retrospective cohort study included 175 participants with T2D divided into three groups: chiglitazar (n = 55), semaglutide (n = 57), and pioglitazone (n = 63). participants underwent a 4-week treatment period. Core metrics, including blood glucose, lipid metabolism indicators, urinary albumin-to-creatinine ratio (UACR), and metabolic insulin resistance score (METS-IR), were assessed before and after treatment to evaluate drug efficacy. RESULTS: Dawn phenomenon: chiglitazar significantly improved dawn phenomenon intensity (Δ0.004 ± 0.80 to -0.77 ± 0.67, p < 0.01), outperforming other drugs. Lipid metabolism: semaglutide demonstrated superior efficacy in reducing total cholesterol (TC) and free fatty acids (FFA) (p < 0.05). Kidney function: both semaglutide and chiglitazar significantly lowered UACR (p < 0.01), with semaglutide showing greater efficacy (-0.13 ± 0.02 versus -0.08 ± 0.01, p < 0.05). Insulin resistance and cardiovascular protection: all three drugs significantly improved METS-IR, with no statistical differences between groups (p > 0.05). SAFETY: all drugs exhibited good tolerability with no severe adverse events. CONCLUSIONS: Chiglitazar is particularly effective for participants with pronounced dawn phenomenon, semaglutide excels in lipid metabolism improvement and kidney protection, while pioglitazone remains effective for insulin resistance and glycemic control. These findings provide evidence-based guidance for individualized T2D management.