2025美国肥胖周热点：双重突破！0602K联手替尔泊肽，协同效应重塑脂肪与肌肉

Core Insights - Obesity is a global epidemic closely linked to insulin resistance and various serious metabolic complications. GLP-1 receptor agonists, particularly the dual-action GLP-1/GIP agonist Tirzepatide, have significantly advanced obesity treatment, but they have limitations such as potential muscle loss and dependence on sustained weight loss for improving insulin sensitivity [6][13]. Treatment Innovations - Azemiglitazone Potassium (0602K) is a new generation insulin sensitizer optimized to avoid the side effects associated with traditional insulin sensitizers that activate metabolic nuclear receptor PPARγ directly. Research suggests that combining 0602K with Tirzepatide could enhance metabolic improvement by acting on both muscle and fat tissues [7][13]. Research Findings - During the 2025 ObesityWeek, Dr. Jerry Colca from Cirius Therapeutics presented findings on the synergistic effects of 0602K and Tirzepatide. In a study using a diet-induced obesity model with C57BL/6J mice, the combination treatment maintained weight loss achieved by Tirzepatide alone and significantly promoted the remodeling of subcutaneous and visceral fat structures while preserving skeletal muscle function [9][11]. Mechanism of Action - The combination therapy was shown to enhance UCP1 expression, effectively increasing the activity of thermogenic pathways in subcutaneous fat. Notably, 0602K alone increased muscle mass, and when combined with Tirzepatide, it altered the muscle transcriptome, significantly upregulating key structural and functional proteins such as myosin and troponin, indicating protective remodeling of skeletal muscle [11][13]. Future Implications - Overall, the experimental data reveal a surprising synergistic effect between 0602K and Tirzepatide, suggesting that combining MPC inhibitors with GLP-1/GIP agonists could promote beneficial remodeling of adipose tissue and mitigate muscle loss associated with monotherapy. This combination may further expand the application prospects in weight management treatments [13].