Tartau Cosmin Gabriel, Boboc Ianis Kevyn Stefan, Mititelu-Tartau Liliana, Bogdan Maria, Buca Beatrice Rozalina, Pavel Liliana Lacramioara, Amalinei Cornelia
Department of Morphofunctional Sciences I, Faculty of Medicine, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania.
Department of Pharmacology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Pharmaceuticals (Basel). 2025 May 1;18(5):670. doi: 10.3390/ph18050670.
Type 2 Diabetes (T2D) is a complex metabolic disorder that affects multiple organs, leading to severe complications in the pancreas, kidneys, liver, and heart. Prolonged hyperglycemia, along with oxidative stress and chronic inflammation, plays a crucial role in accelerating tissue damage, significantly increasing the risk of diabetic complications such as nephropathy, hepatopathy, and cardiovascular disease. This review evaluates the protective effects of various antidiabetic treatments on organ tissues affected by T2D, based on findings from experimental animal models. Metformin, a first-line antidiabetic agent, has been widely recognized for its ability to reduce inflammation and oxidative stress, thereby mitigating diabetes-induced organ damage. Its protective role extends beyond glucose regulation, offering benefits such as improved mitochondrial function and reduced fibrosis in affected tissues. In addition to traditional therapies, new classes of antidiabetic drugs, including sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists not only improve glycemic control but also exhibit nephroprotective and cardioprotective properties by reducing glomerular hyperfiltration, oxidative stress, and inflammation. Similarly, GLP-1 receptor agonists have been associated with reduced hepatic steatosis and enhanced cardiovascular function. Preclinical studies suggest that tirzepatide, a dual GLP-1/gastric inhibitory polypeptide receptor agonist may offer superior metabolic benefits compared to conventional GLP-1 agonists by improving β-cell function, enhancing insulin sensitivity, and reducing fatty liver progression. Despite promising preclinical results, differences between animal models and human physiology pose a challenge. Further clinical research is needed to confirm these effects and refine treatment strategies. Future T2D management aims to go beyond glycemic control, emphasizing organ protection and long-term disease prevention.
2型糖尿病（T2D）是一种复杂的代谢紊乱疾病，会影响多个器官，导致胰腺、肾脏、肝脏和心脏出现严重并发症。长期高血糖，连同氧化应激和慢性炎症，在加速组织损伤方面起着关键作用，显著增加了糖尿病并发症如肾病、肝病和心血管疾病的风险。本综述基于实验动物模型的研究结果，评估了各种抗糖尿病治疗对受T2D影响的器官组织的保护作用。二甲双胍作为一线抗糖尿病药物，因其能够减轻炎症和氧化应激，从而减轻糖尿病引起的器官损伤而被广泛认可。其保护作用不仅限于血糖调节，还能改善线粒体功能，减少受影响组织的纤维化等。除了传统疗法外，新型抗糖尿病药物，包括钠-葡萄糖协同转运蛋白2抑制剂和胰高血糖素样肽-1（GLP-1）受体激动剂，不仅能改善血糖控制，还通过减少肾小球高滤过、氧化应激和炎症表现出肾脏保护和心脏保护特性。同样，GLP-1受体激动剂与减少肝脂肪变性和增强心血管功能有关。临床前研究表明，双重GLP-1/胃抑制多肽受体激动剂替尔泊肽通过改善β细胞功能、增强胰岛素敏感性和减少脂肪肝进展，可能比传统GLP-1激动剂提供更好的代谢益处。尽管临床前结果很有前景，但动物模型与人体生理学之间的差异带来了挑战。需要进一步的临床研究来证实这些作用并完善治疗策略。未来T2D的管理旨在超越血糖控制，强调器官保护和长期疾病预防。
