Li Wenxuan, Wang Yangang, Liu Chuanfeng, Yu Yongzhuo, Xu Lili, Dong Bingzi
The Affiliated Hospital of Qingdao University, Qingdao, China.
Diabetes Ther. 2025 Apr;16(4):731-748. doi: 10.1007/s13300-025-01708-9. Epub 2025 Feb 28.
The dawn phenomenon (DP), characterized by early morning hyperglycemia, poses a significant challenge in diabetes management and is associated with increased glycemic variability and long-term complications. Despite its clinical impact, effective therapeutic strategies remain limited. Chiglitazar, a novel pan-PPAR agonist, has demonstrated benefits in improving lipid metabolism and insulin sensitivity, but its potential role in mitigating DP remains unexplored. This study evaluates the regulatory effect of chiglitazar on DP and investigates its possible mechanisms beyond lipid modulation.
This retrospective observational study included 22 hospitalized diabetic patients who received chiglitazar (20 mg). Blood glucose levels at 3:00 a.m. and fasting glucose levels over three consecutive days were measured pre- and post-treatment, and the dawn phenomenon intensity was calculated. Lipid profiles were assessed to explore potential correlations with glucose changes.
Following chiglitazar administration, significant reductions were observed in LDL-C (43.82 ± 18.27 vs. 36.97 ± 16.90, p < 0.05), FFA (6.00 ± 2.38 vs. 5.06 ± 1.77, p < 0.05), mean 3:00 a.m. blood glucose (Z = - 2.03, p < 0.05), and fasting blood glucose (Z = - 2.96, p < 0.05). DP intensity also significantly improved (Z = - 3.48, p < 0.01). However, no significant correlation was found between glucose improvements and lipid profile changes (p > 0.05), suggesting an alternative mechanism of action.
Chiglitazar effectively reduces DP intensity and improves glycemic control, independent of its effects on lipid metabolism. These findings suggest a potential link between chiglitazar's mechanism and circadian rhythm regulation, possibly through the modulation of REV-ERB nuclear receptors. Further research is needed to confirm this hypothesis and evaluate the long-term clinical benefits of chiglitazar in diabetes management.
黎明现象（DP）以清晨高血糖为特征，给糖尿病管理带来了重大挑战，并且与血糖变异性增加及长期并发症相关。尽管其具有临床影响，但有效的治疗策略仍然有限。新型泛过氧化物酶体增殖物激活受体（PPAR）激动剂西格列他扎已显示出在改善脂质代谢和胰岛素敏感性方面的益处，但其在减轻黎明现象方面的潜在作用仍未得到探索。本研究评估西格列他扎对黎明现象的调节作用，并研究其除脂质调节之外的可能机制。
这项回顾性观察性研究纳入了22例接受西格列他扎（20毫克）治疗的住院糖尿病患者。在治疗前后测量凌晨3点的血糖水平和连续三天的空腹血糖水平，并计算黎明现象强度。评估血脂谱以探索与血糖变化的潜在相关性。
服用西格列他扎后，低密度脂蛋白胆固醇（LDL-C）（43.82±18.27对36.97±16.90，p<0.05）、游离脂肪酸（FFA）（6.00±2.38对5.06±1.77，p<0.05）、凌晨3点平均血糖（Z=-2.03，p<0.05）和空腹血糖（Z=-2.96，p<0.05）均显著降低。黎明现象强度也显著改善（Z=-3.48，p<0.01）。然而，血糖改善与血脂谱变化之间未发现显著相关性（p>0.05），提示存在其他作用机制。
西格列他扎可有效降低黎明现象强度并改善血糖控制，与其对脂质代谢的影响无关。这些发现提示西格列他扎的作用机制与昼夜节律调节之间可能存在联系，可能是通过调节REV-ERB核受体实现的。需要进一步研究来证实这一假设，并评估西格列他扎在糖尿病管理中的长期临床益处。
