Positive impact of DPP-4 or SGLT2 inhibitors on mild cognitive impairment in type 2 diabetes patients on metformin therapy: A metabolomic mechanistic insight

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy Pub Date : 2025-01-01 DOI:10.1016/j.biopha.2024.117771

Shams T. Osman , Waziha Purba , Oluwatosin Daramola , Md Mostofa Al Amin Bhuiyan , Judith Nwaiwu , Mojibola Fowowe , Junyao Wang , Noha A. Hamdy , Mahmoud A. Agami , Amr Y. El-Feky , Labiba K. El-Khordagui , Yehia S. Mechref , Ahmed F. El-Yazbi

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引用次数: 0

Abstract

Mild cognitive impairment is increasingly recognized as a complication of type 2 diabetes (T2D). Although currently no disease-modifying treatments for cognitive disorders exist, interest surged in potential neuroprotective effects of newer anti-diabetic drugs. This study investigates the impact of newer anti-diabetic drug classes, dipeptidyl peptidase-4 (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) - on cognitive decline in T2D patients on metformin therapy. A prospective observational cohort study was conducted, with a follow-up duration of 6 months. The study compared the cognitive performance of T2D patients on metformin monotherapy to those on a combination of metformin with DPP-4i or SGLT2i, using the Montreal Cognitive Assessment Battery. A group of healthy volunteers served as a reference. At baseline, patients receiving combination therapy had a cognitive performance comparable to that of healthy volunteers, while those on metformin monotherapy scored lower. These differences persisted for patients who completed the follow-up, though there was no change within group. Baseline differences were independent of glycemic control, blood lipids, renal function, and serum inflammatory markers. Comprehensive metabolomics and lipidomics revealed that T2D patients on metformin monotherapy exhibited enriched purine, glutathione and sphingolipid metabolism, with alterations in xanthine, L-pyroglutamic acid, and several sphingomyelins. These changes suggest increased oxidative stress in T2D, mitigated in the combination therapy group, as evidenced by total serum antioxidant capacity. As such, we conclude that the combination of DPP-4i or SGLT2i with metformin positively impacts cognitive function in T2D patients by modulating metabolic pathways rather than improving glycemic control, peripheral diabetic complications, or systemic inflammation.

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DPP-4或SGLT2抑制剂对二甲双胍治疗的2型糖尿病患者轻度认知障碍的积极影响：代谢组学机制的见解

轻度认知障碍越来越被认为是2型糖尿病（T2D）的并发症。尽管目前还没有针对认知障碍的疾病改善疗法，但人们对新型抗糖尿病药物潜在的神经保护作用的兴趣激增。本研究探讨了新型抗糖尿病药物，二肽基肽酶-4 （DPP-4i）和钠-葡萄糖共转运蛋白-2抑制剂(SGLT2i) -对二甲双胍治疗的T2D患者认知能力下降的影响。采用前瞻性观察队列研究，随访6个月。该研究比较了二甲双胍单药治疗与二甲双胍与DPP-4i或SGLT2i联合治疗的T2D患者的认知表现，使用蒙特利尔认知评估电池。一组健康的志愿者作为参考。在基线时，接受联合治疗的患者的认知表现与健康志愿者相当，而接受二甲双胍单药治疗的患者得分较低。这些差异在完成随访的患者中持续存在，尽管在组内没有变化。基线差异与血糖控制、血脂、肾功能和血清炎症标志物无关。综合代谢组学和脂质组学显示，二甲双胍单药治疗的T2D患者嘌呤、谷胱甘肽和鞘脂代谢丰富，黄嘌呤、l -焦谷氨酸和几种鞘磷脂发生改变。这些变化表明T2D氧化应激增加，在联合治疗组减轻，如血清总抗氧化能力所证明的那样。因此，我们得出结论，DPP-4i或SGLT2i联合二甲双胍通过调节代谢途径而不是改善血糖控制、外周糖尿病并发症或全身性炎症，对T2D患者的认知功能产生积极影响。

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来源期刊

Biomedicine & Pharmacotherapy 医学-药学

CiteScore

11.90

自引率

2.70%

发文量

1621

审稿时长

48 days

期刊介绍： Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.