Protective Effect of SGLT2 Inhibitor on D-Galactose-Induced Senescence in Mice and Its Mechanism

Objective: To observe the cerebral protective effect of dagliflozin, a sodium-glucose co-transport protein 2 (SGLT2) inhibitor, in aging mice and to explore its molecular mechanism. Methods: 1. 66 male C57BL/6 mice were divided into control group (13) and model group (53), and the model group was moulded by subcutaneous injection of D-galactose into the back of the neck, while the control group was treated with equal amount of saline for 8 weeks. The weight of each group of mice was observed and recorded every 7 days, and two groups of mice were randomly selected for frozen sections of brain tissue at the end of the modelling period to verify the aging model. 2. After the aging model was successfully established, the aging groups were divided into 5 groups: model group, dagliflozin-treated group (high and low dose), and dagliflozin + ex527-inhibited group (high and low dose). Fasting blood glucose was measured in each group every 2 weeks for 8 weeks. At the end of treatment, Morris water maze was performed at the end of the treatment. After execution of the mice, the organ indices of heart, brain, liver, kidney and spleen were measured;the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum were determined. Results: After the successful establishment of the aging model, it was found that during the treatment phase of dagliflozin. 1) The organ indices of mice in the aging group were significantly lower than those of other groups, and no significant hypoglycemia was observed throughout the treatment process. 2) In the water maze test, mice in the aging group had a significantly longer latency in the plateau phase compared to the control and treatment groups, while the number of times the mice crossed the original plateau and the percentage of time spent exploring the original plateau quadrant were reduced after the plateau was removed. 3) The nerve cells in the aging mice were disorganized and the nuclei of the mice were deeply stained;the dagliflozin group improved the morphological changes in the brain of aging mice. 4) In addition, compared with the control mice, the serum MDA level was significantly increased and the antioxidant enzyme SOD activity was significantly decreased in the aging group, while compared with the aging group, dagliflozin significantly decreased the MDA level and increased the SOD activity. 5) The expression of SIRT1 and PGC-1α was significantly upregulated in the low and high doses of dagliflozin compared to the aging group. Conclusion: The present study suggests that dagliflozin can delay organ aging, improve the learning and memory ability of aging mice, and exert antioxidant effects, probably through upregulating the SIRT1/PGC-1α signaling pathway.

A Fluorescent Glucose Transport Assay for Screening SGLT2 Inhibitors in Endogenous SGLT2-Expressing HK-2 Cells

The sodium-dependent glucose transporters 2(SGLT2)plays important role in renal reabsorption of urinal glucose back to plasma for maintaining glucose homeostasis.The approval of SGLT2 inhibitors for treatment of type 2 diabetes highlights the SGLT2 as a feasible and promising drug target in recent years.Current methods for screening SGLT2 inhibitors are complex,expensive and labor intensive.Particularly,these methods cannot directly measure nonradioactive glucose uptake in endogenous SGLT2-expressing kidney cells.In present work,human kidney cells,HK-2,was incubated with a fluorescent D-glucose derivant 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose(2-NBDG)and the fluorescent intensity of 2-NBDG was employed to measure the amount of glucose uptake into the cells.By optimizing the passages of HK-2 cells,2-NBDG concentration and incubation time,and by measuring glucose uptake treated by Dapagliflozin,a clinical drug of SGLT2 inhibitors,we successfully developed a new assay for measuring glucose uptake through SGLT2.The nonradioactive microplate and microscope-based high-throughput screening assay for measuring glucose can be a new method for screening of SGLT2 inhibitors and implied for other cell assays for glucose measurement extensively.

A review of potential mechanisms and uses of SGLT2 inhibitors in ischemia-reperfusion phenomena

Recently added to the therapeutic arsenal against chronic heart failure as a first intention drug,the antidiabetic drug-class sodium-glucose cotransporter-2 inhibitors(SGLT2i)showed efficacy in decreasing overall mortality,hospitalization,and sudden death in patients of this very population,in whom chronic or acute ischemia count among the first cause.Remarkably,this benefit was observed independently from diabetic status,and benefited both preserved and altered ventricular ejection fraction.This feature,observed in several large randomized controlled trials,suggests additional effects from SGLT2i beyond isolated glycemia control.Indeed,both in-vitro and animal models suggest that inhibiting the Na+/H+exchanger(NHE)may be key to preventing ischemia/reperfusion injuries,and by extension may hold a similar role in ischemic damage control and ischemic preconditioning.Yet,several other mechanisms may be explored which may help better target those who may benefit most from SGLT2i molecules.Because of a large therapeutic margin with few adverse events,ease of prescription and potential pharmacological efficacity,SGLT2i could be candidate for wider indications.In this review,we aim to summarize all evidence which link SGLT2i and ischemia/reperfusion injuries modulation,by first listing known mechanisms,including metabolic switch,prevention of lethal arrythmias and others,which portend the latter,and second,hypothesize how the former may interact with these mechanisms.

Structural repurposing of SGLT2 inhibitor empagliflozin for strengthening anti-heart failure activity with lower glycosuria

Sodium-glucose cotransporter 2(SGLT2)inhibitors have been reapproved for heart failure(HF)therapy in patients with and without diabetes.However,the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice.A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect.To address this issue,we conducted structural repurposing of EMPA,a representative SGLT2 inhibitor,to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2.Compared to EMPA,the optimal derivative JX01,which was produced by methylation of C2—OH of the glucose ring,exhibited weaker SGLT2-inhibitory activity(IC_(50)>100 nmol/L),and lower glycosuria and glucose-lowering side-effect,better NHE1-inhibitory activity and cardioprotective effect in HF mice.Furthermore,JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity,and good pharmacokinetic properties in both mouse and rat species.Collectively,the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs,and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

Sodium glucose cotransporter-2 inhibitors and heart disease:Current perspectives

Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are antidiabetic medications with remarkable cardiovascular(CV)benefits proven by multiple randomised controlled trials and real-world data.These drugs are also useful in the prevention of CV disease(CVD)in patients with diabetes mellitus(DM).Although DM as such is a huge risk factor for CVD,the CV benefits of SGLT-2i are not just because of antidiabetic effects.These molecules have proven beneficial roles in prevention and management of nondiabetic CVD and renal disease as well.There are various molecular mechanisms for the organ protective effects of SGLT-2i which are still being elucidated.Proper understanding of the role of SGLT-2i in prevention and management of CVD is important not only for the cardiologists but also for other specialists caring for various illnesses which can directly or indirectly impact care of heart diseases.This clinical review compiles the current evidence on the rational use of SGLT-2i in clinical practice.

非奈利酮与SGLT2抑制剂对2型糖尿病和/或慢性肾脏病患者心血管事件的影响

目的比较非奈利酮与钠-葡萄糖共转运蛋白-2(sodium-glucose cotransporter-2,SGLT2)抑制剂对2型糖尿病和/或慢性肾脏病患者心血管事件的影响。方法检索PubMed、Cochrane Library、Web of Science和Embase数据库关于2型糖尿病和/或慢性肾脏病患者的随机对照试验,时间为建库至2023年7月3日。基于频率模型,使用STATA 17.0软件进行网状荟萃分析(network meta-analysis,NMA)。结果共纳入7项随机对照试验,包括33206例患者。涉及的治疗方式包括非奈利酮和SGLT2抑制剂,其中SGLT2抑制剂包含恩格列净、卡格列净、达格列净和索格列净(双重SGLT抑制剂)。在心血管复合事件方面,根据累计曲线下的概率面积(surface under the cumulative ranking area,SUCRA)排序,索格列净最有效。在心血管死亡方面,根据SUCRA排序,恩格列净最有效。在心力衰竭住院方面,根据SUCRA排序,卡格列净最有效。在全因死亡方面,根据SUCRA排序,达格列净最有效。非奈利酮和SGLT2抑制剂在不良事件、严重不良事件和急性肾损害的安全性方面比较,差异均无统计学意义(均P>0.05)。与采用非奈利酮治疗的患者相比,采用SGLT2抑制剂治疗的患者高钾血症发生率更低(RR=0.41,95%CI 0.32~0.52)。结论与非奈利酮相比,SGLT2抑制剂能更好地降低心血管事件的发生率,可作为2型糖尿病和/或慢性肾脏病患者的基础治疗,帮助预防或减少心血管事件。

SGLT2抑制剂对动脉粥样硬化神经保护作用机制研究进展

动脉粥样硬化是一种多发性的血管内膜病变,易累及冠状动脉和脑动脉,是冠心病、高血压、脑卒中等心脑血管疾病的主要病理基础。动脉粥样硬化与认知障碍的发生密切相关,而糖尿病和动脉粥样硬化二者又互为危险因素,故临床中糖尿病患者是动脉粥样硬化和认知障碍的高危人群。钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)是近年来上市的新型降糖药物,多项研究表明其对动脉粥样硬化和神经具有保护作用。其保护作用机制是多途径的。包括降低促炎细胞因子,M2巨噬细胞极化,抑制STAT1和NLRP3炎症小体及减轻氧化应激反应。同时SGLT2i也能改善内皮功能,防止重构,对神经血管单位、血脑屏障、周细胞、少突胶质细胞等具有保护作用。据研究SGLT2i还可以显著提高脑源性神经营养因子(BDNF)水平以及恢复mTOR激活的昼夜节律,降低动脉粥样硬化的程度,且能调节神经传递,确保神经元的生长、生存和可塑性。本文就SGLT2i对动脉粥样硬化及神经的保护作用机制最新进展展开综述,以期为临床进一步治疗动脉粥样硬化、认知障碍等相关心脑血管疾病提供新的思路。

二甲双胍联合SGLT2抑制剂治疗PCOS合并T2DM患者的研究进展

多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者常合并2型糖尿病(type 2 diabetes mellitus,T2DM),二者在病因及发病机制上相互联系及影响。二甲双胍是T2DM的基础用药,临床上也用于PCOS,但单用的治疗效果有限,联合其他药物成为治疗的重要选择。钠-葡萄糖协同转运蛋白2(sodium-glucose cotransporter 2,SGLT-2)抑制剂作为一类有其独特的作用机制的药物,具有良好的治疗效果和广阔的应用范围。现在考虑二甲双胍联用SGLT2抑制剂治疗PCOS合并T2DM患者,本文对二甲双胍联用SGLT2抑制剂治疗PCOS合并T2DM患者的研究进展及作用机制进行综述。

Cardioprotective mechanism of SGLT2 inhibitor against myocardial infarction is through reduction of autosis

Sodium-glucose cotransporter 2(SGLT2)inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains elusive.Here we demonstrated that the SGLT2 inhibitor,Empagliflozin(EMPA),suppresses cardiomyocytes autosis(autophagic cell death)to confer cardioprotective effects.Using myocardial infarction(Ml)mouse models with and without diabetes mellitus,EMPA treatment significantly reduced infarct size,and myocardial fibrosis,thereby leading to improved cardiac function and survival.In the context of ischemia and nutritional glucose deprivation where autosis is already highly stimulated,EMPA directly inhibits the activity of the Na^(+)/H^(+)exchanger 1(NHE1)in the cardiomyocytes to regulate excessive autophagy.Knockdown of NHE1 significantly rescued glucose deprivation-induced autosis.In contrast,overexpression of NHE1 aggravated the cardiomyocytes death in response to starvation,which was effectively rescued by EMPA treatment.Furthermore,in vitro and in vivo analysis of NHE1 and Beclin 1 knockout mice validated that EMPA s cardioprotective effects are at least in part through downregulation of autophagic flux.These findings provide new insights for drug development,specifically targeting NHE1 and autosis for ventricular remodeling and heart failure after Ml in both diabetic and non-diabetic patients.

Design,synthesis and biological activity of cyclohexane-bearing C-glucoside derivatives as SGLT2 inhibitors

Seven cyclohexane-bearing C-glucoside derivatives（7,9,12,13 and 17-19） were designed and synthesized as SGLT2 inhibitors starting from a potent SGLT2 inhibitor we discovered in earlier work, （lS）-1-deoxy-l-[4-methoxy-3-（trans-n-propylcyclohexyl）methylphenyl]-D-glucose（1）.The in vitro and in vivo biological activities were evaluated by hSGLT2/hSGLTl inhibition and urinary glucose excretion （UGE）,respectively.Among the synthesized compounds 12,the 6-deoxy derivative of 1 was the most active and selective SGLT2 inhibitor（IC_（50）= 1.4nmol/L against hSGLT2;selectivity = 1576）.Compound 12 was a potent SGLT2 inhibitor,which could induce more urinary glucose than 1 and dapagliflozin in UGE.

3-Oxodapagliflozin as a Potent and Highly Selective SGLT2 Inhibitor for the Treatment of Type 2 Diabetes

Structural modifications of 3-OH in the glucose moiety of dapagliflozin（1）, an approved potent sodium-dependent glucose transporter 2（SGLT2） inhibitor, led to 3-oxodapagliflozin（16）, a highly potent and more selective SGLT2 inhibitor[IC50（hSGLT1）/IC50（hSGLT2）=2851 for compound 16 vs. 843 for compound 1]. 3-Oxodapagliflozin（16） exhibited in vitro（IC50=1.0nmol/L against hSGLT2 for compound 16 vs. 1.3 nmol/L for compound 1） and in vivo activities comparable to those of dapagliflozin（1）. The bioactivities of 3-oxodapagliflozin （16） warrant its further evaluation as a promising SGLT2 inhibitor for the treatment of type 2 diabetes.

A cell-based fluorescent glucose transporter assay for SGLT2 inhibitor discovery

The sodium/glucose cotransporter 2(SGLT2)is responsible for the majority of glucose reabsorption in the kidney,and currently,SGLT2 inhibitors are considered as promising hypoglycemic agents for the treatment of type 2 diabetes mellitus.By constructing CHO cell lines that stably express the human SGLT2 transmembrane protein,along with a fluorescent glucose transporter assay that uses 2-[N-(7-nitrobenz-2-oxa-l,3-diazol-4-yl)amino]2-deoxyglucose(2-NBDG)as a glucose analog,we have developed a nonradioactive,cell-based assay for the discovery and characterization of SGLT2 inhibitors.

SGLT2抑制剂对糖尿病小鼠炎性因子表达的影响

目的探讨糖尿病小鼠血管内皮炎性因子是否表达,SGLT2抑制剂对其作用的影响。方法将8周龄SPF级雄性CIR小鼠腹腔注射低剂量STZ(50 mg/kg),建模持续6 d,对照组皮下注射生理盐水,造模成功,随机分成对照组(普通饲料),模型组(普通饲料)和治疗组(普通饲料+达格列净干预治疗),动态观察4周、8周、12周末小鼠的体重、血糖变化,分别应用EILSA法检测血浆内肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、单核细胞趋化因子-1(MCP-1)表达变化和Western blot法测定血管壁各炎性因子蛋白的表达。结果各组小鼠体重和血糖在不同时间段比较,差异有统计学意义(P<0.05)。与对照组比较4周模型组血浆内TNF-α显著升高,差异有统计学意义(P<0.01),而4周模型组血浆内IL-1β、MCP-1表达亦增多,差异无统计学意义(P>0.05);与对照组比较8周、12周模型组血浆内TNF-α、IL-1β、MCP-1表达变化明显升高,差异有统计学意义(P<0.05);与模型组比较4周治疗组血浆内TNF-α、IL-1β、MCP-1表达变化不明显,差异无统计学意义(P>0.05);与治疗组比较8周、12周时模型组血浆内TNF-α、IL-1β、MCP-1表达变化明显下降,差异有统计学意义(P<0.05)。12周末血管壁组织内各炎性因子蛋白表达有变化,差异有统计学意义(P<0.05)。结论SGLT2抑制剂能有效抑制糖尿病小鼠血管内皮细胞内炎性因子的释放。

SGLT2抑制剂治疗2型糖尿病肾病效果及与SUA Smad1蛋白脂蛋白的相关性

目的:观察SGLT2抑制剂治疗2型糖尿病肾病(Type 2 diabetic nephropathy,T2DN)效果,分析T2DN与血尿酸(Serum uric acid,SUA)、Smad1蛋白、脂蛋白的相关性。方法:回顾性分析本院2020年4月至2022年3月收治的72例T2DN患者的临床资料(研究组),根据患者尿白蛋白排泄率(Urinary albumin excretion rate,UAER),统计早期糖尿病肾病(UAER 30-300mg/24h)、临床糖尿病肾病(UAER>300mg/24h)者例数,连续接受3个月的SGLT2抑制剂治疗(10mg/次,1d/次)后,评估治疗效果及不良反应。另选取同期在本院进行健康体检的54例健康者作为对照组。对比不同人群SUA、Smad1蛋白、脂蛋白的水平,采用Spearman分析上述因子与UAER间的相关性。结果:研究组SUA、Smad1蛋白、脂蛋白水平均高于对照组(P<0.05)。72例T2DN患者经治疗后总有效率为87.50%(63/72),不良反应总发生率为9.72%(7/72)。治疗后,T2DN患者SUA、Smad1蛋白、脂蛋白水平较治疗前降低(P<0.05)。经统计,早期糖尿病肾病组45例,临床糖尿病肾病组27例。治疗前,早期糖尿病肾病组SUA、Smad1蛋白及脂蛋白水平均低于临床糖尿病肾病组(P<0.05)。治疗后,两组患者SUA、Smad1蛋白、脂蛋白水平较治疗前降低,其中早期糖尿病肾病组低于临床糖尿病肾病组(P<0.05)。Spearman分析结果显示:SUA、Smad1蛋白、脂蛋白表达与UAER均呈正相关关系(P<0.001)。结论:SUA、Smad1蛋白、脂蛋白在T2DN患者中呈高表达,经SGLT2抑制剂治疗可降低SUA、Smad1蛋白、脂蛋白的水平,不良反应低。临床通过检测SUA、Smad1蛋白、脂蛋白水平,可反映患者肾损伤程度,对制定治疗方案有一定指导价值。

Design,synthesis and in vivo anti-hyperglycemic activity of gem-dimethyl-bearing C-glucosides as SGLT2 inhibitors

一系列 gem-dimethyl-bearing C 配糖物被设计并且作为 SGLT2 禁止者综合了，与无水的铝构造是的 gem-dimethyl 功能的调停氯化物的 Friedel 手艺完化关键步。在里面 vivo anti-hyperglycemic 活动带着老鼠被评估口头的葡萄糖忍耐测试(OGTT ) ，和重要的显示出的所有综合混合物但是更少的有势力 anti-hyperglycemic 活动比积极控制 dapagliflozin。

Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors in Type 2 Diabetes: A Literature Review of Approved Products

Diabetes mellitus continues to be a major health issue worldwide. Despite all of the treatment options available on the market, many patients with diabetes fail to reach their treatment goals. Novel agents such as the Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors show promise in effectively lowering blood glucose. Objective: To review the scientific literature for efficacy information regarding the use of approved SGLT2 inhibitors (canagliflozin, dapagliflozin and empagliflozin) in the treatment of Type 2 Diabetes Mellitus (T2DM). Methods: A MEDLINE (1950-August 2014) literature review was performed. All of the literature published as an original clinical trial was included in this review. Other pertinent articles published related to the original clinical trial were also included. Meta-analysis type studies were not selected for this review. Conclusions: With an increasing prevalence and incidence of type 2 diabetes mellitus worldwide, there is an apparent need for effective therapeutic strategies to combat this chronic and progressive disease. SGLT2 inhibitors offer this potential. Recently approved agents (canagliflozin, dapagliflozin and empagliflozin) have shown significant promise as mono- and add-on therapy to current glucose-lowering regimens that may not otherwise be providing sufficient glycemic control in T2DM patients.

合并炎症性肠病的糖原累积病-Ⅰb型5例患儿SGLT2抑制剂治疗效果分析

目的分析5例合并炎症性肠病(IBD)的糖原累积病-Ⅰb型(GSD-Ⅰb)患儿接受钠-葡萄糖共转运体2(SGLT2)抑制剂的治疗效果。方法回顾性分析2021—2022年接受治疗并随访的5例合并IBD的GSD-Ⅰb型患儿,SGLT2抑制剂治疗前后的临床表现、实验室及辅助检查。结果5例患儿IBD发作中位年龄为5.0岁。5例均有口腔溃疡、腹痛、腹泻及肛周脓肿。SGLT2抑制剂治疗前,5例的中位儿童克罗恩病活动指数(PCDAI)为55.0。SGLT2抑制剂中位治疗12.0月后[末次随访中位剂量0.31 mg/(kg·d)],中位PCDAI(10.0)显著降低(P=0.043),5例均获得临床应答。治疗中,2例出现低血糖,4例出现会阴部或尿道口瘙痒。发现2种新SLC 37A4变异(c.2delT,c.1065delG)。c.446G>A(p.G 149E)为热点变异(70%)。结论SGLT2抑制剂可明显改善GSD-Ⅰb型患儿的IBD活动度,且安全性良好。

基于CiteSpace的SGLT2抑制剂治疗心力衰竭的可视化分析

目的采用CiteSpace软件可视化分析钠葡萄糖协同转运蛋白2(SGLT2)抑制剂治疗心力衰竭(HF)相关研究的文献篇数、发文作者、研究机构以及关键词,探索SGLT2抑制剂治疗HF的发展状况、研究热点及研究前沿。方法以Web of Science核心合集数据库为检索源,基于Java平台的文献计量学CiteSpace V软件对纳入的文献进行处理分析,并得出相关知识图谱。结果Web of Science数据库自1997年发布以来收录的关于SGLT2抑制剂治疗HF研究的英文文章最早发表于2012年,该领域发文数量从2012—2021年呈上升趋势,说明该领域仍处于发展阶段。本研究共纳入文献1051篇,美国共发文471篇,为该领域发文量最多的国家。发文数量最多的研究机构是加拿大的多伦多大学,各研究机构之间合作较少,且较为分散。可视化分析后得出该领域研究热点主要为糖尿病、心血管疾病及慢性肾病在SGLT2抑制剂治疗中的获益及其作用机制。结论该领域目前的研究热点之一是HF在运用SGLT2抑制剂治疗中的获益情况,逐步拓展到其他心血管疾病如房颤、心肌梗死等及慢性肾病患者在运用SGLT2抑制剂治疗中是否获益,这类药物可以改善糖尿病患者的预后、降低HF患者的死亡率、减少糖尿病患者肾功能衰竭的发生,并可以通过优化血容量起到一定的降压等作用,且目前只有SGLT2抑制剂具备以上多重功效。故推测,SGLT2抑制剂具有广阔的临床应用前景。

SGLT2抑制剂在冠心病中的作用机制的研究进展

钠葡萄糖协同转运蛋白2抑制剂(sodium-dependent glucose transporters 2 inhibitors,SGLT2i)被广泛应用于降糖治疗,并且已被推荐为Ⅰ类药物治疗心力衰竭。然而,SGLT2i在冠心病中的作用和机制尚无准确定论。本文概述了SGLT2i在冠心病中的药理作用和相关机制,特别是其改善血管内皮功能的作用;同时讨论了相关研究的局限性和未来的研究方向。该综述对SGLT2i在冠心病中的研究提供了新的思路和参考,对于临床应用和科研方向具有重要意义。

SGLT2抑制剂联合二甲双胍治疗对糖尿病肾病患者血糖及疗效的影响

目的分析钠-葡萄糖共转运蛋白2(sodium-dependent glucose transporters 2,SGLT2)抑制剂联合二甲双胍治疗对糖尿病肾病患者血糖及疗效的影响。方法选取2021年1月—2023年1月福建省立医院接诊的108例糖尿病肾病患者,按照随机数表法分为对照组与研究组,各54例。对照组接受二甲双胍+百令胶囊治疗,研究组联合SGLT2抑制剂治疗,分析对比两组患者血糖指标、临床总有效率、肾功能指标及血清炎症指标。结果与对照组相比,研究组治疗后的空腹血糖、餐后2 h血糖及糖化血红蛋白水平更低,差异有统计学意义(P<0.05)。与对照组对比,研究组临床总有效率更高,差异有统计学意义(P<0.05)。与对照组对比,研究组治疗后的血肌酐、尿素氮及尿白蛋白排泄率更低,差异有统计学意义(P<0.05)。结论SGLT2抑制剂联合二甲双胍治疗糖尿病肾病可降低血糖水平,改善肾功能,减轻机体炎症反应,提高临床总效率。