Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus:A real-world experience

BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(RCTs).However,real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.AIM To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.METHODS We evaluated the comparative efficacy data of 3 SGLT-2i drugs(dapagliflozin,canagliflozin,and empagliflozin)used for treating patients with type 2 diabetes mellitus.Data on the reduction of glycated hemoglobin(HbA1c),body weight,blood pressure(BP),urine albumin creatinine ratio(ACR),and adverse effects were recorded retrospectively.RESULTS Data from 467 patients with a median age of 64(14.8)years,294(62.96%)males and 375(80.5%)Caucasians were analysed.Median diabetes duration was 16.0(9.0)years,and the duration of SGLT-2i use was 3.6(2.1)years.SGLT-2i molecules used were dapagliflozin 10 mg(n=227;48.6%),canagliflozin 300 mg(n=160;34.3%),and empagliflozin 25 mg(n=80;17.1).Baseline median(interquartile range)HbA1c in mmol/mol were:dapagliflozin-78.0(25.3),canagliflozin-80.0(25.5),and empagliflozin-75.0(23.5)respectively.The respective median HbA1c reduction at 12 months and the latest review(just prior to the study)were:66.5(22.8)&69.0(24.0),67.0(16.3)&66.0(28.0),and 67.0(22.5)&66.5(25.8)respectively(P<0.001 for all comparisons from baseline).Significant improvements in body weight(in kilograms)from baseline to study end were noticed with dapagliflozin-101(29.5)to 92.2(25.6),and canagliflozin 100(28.3)to 95.3(27.5)only.Significant reductions in median systolic and diastolic BP,from 144(21)mmHg to 139(23)mmHg;(P=0.015),and from 82(16)mmHg to 78(19)mmHg;(P<0.001)respectively were also observed.A significant reduction of microalbuminuria was observed with canagliflozin only[ACR 14.6(42.6)at baseline to 8.9(23.7)at the study end;P=0.043].Adverse effects of SGLT-2i were as follows:genital thrush and urinary infection-20(8.8%)&17(7.5%)with dapagliflozin;9(5.6%)&5(3.13%)with canagliflozin;and 4(5%)&4(5%)with empagliflozin.Diabetic ketoacidosis was observed in 4(1.8%)with dapagliflozin and 1(0.63%)with canagliflozin.CONCLUSION Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c,body weight,and better than those reported in RCTs,with low side effect profiles.A review of large-scale real-world data is needed to inform better clinical practice decision making.

Sodium-Glucose Cotransporter-2 Inhibitors: Who, When & How? Guidance for Use from a Multidisciplinary Practical Approach

Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) have transformed diabetes management by targeting renal glucose reabsorption. Designed initially as antidiabetic agents, their ability to lower blood glucose levels independently of insulin is well-documented. Beyond glycemic control, emerging research has unveiled their profound cardiorenal benefits. By inhibiting SGLT-2 protein, these drugs enhance glucose excretion in urine, reducing blood glucose levels. This mechanism has translated into significant cardiovascular and renal protection, establishing SGLT-2 inhibitors as pivotal in managing not only diabetes but also cardiovascular and renal diseases. Recent studies have illuminated the broader therapeutic potential of SGLT-2 inhibitors beyond diabetes. Evidence indicates their efficacy in managing heart failure, chronic kidney disease (CKD), and cardiovascular complications in individuals with or without diabetes. This expanded therapeutic landscape has catalyzed a paradigm shift in SGLT-2 inhibitor use, positioning them as key agents in the cardiorenal metabolic continuum. Moreover, their role in the secondary prevention of cardiovascular events and slowing CKD progression in T2DM patients has garnered considerable attention. This consensus-based review aims to offer practical guidance in an algorithmic approach to primary care healthcare professionals to optimize SGLT-2 inhibitors utilization and maximize their benefits. The review seeks to empower clinicians to effectively manage patients who may benefit from SGLT-2 inhibitor therapy by addressing common initiation barriers and optimizing treatment strategies. Additionally, it aims to raise awareness among primary care physicians regarding the multifaceted benefits of these medications and overcome clinical inertia in their adoption into routine clinical practice.

Heterogeneity in cardiorenal protection by Sodium glucose cotransporter 2 inhibitors in heart failure across the ejection fraction strata:Systematic review and meta-analysis

BACKGROUND Gliflozins or Sodium glucose cotransporter 2 inhibitors(SGLT2i)are relatively novel antidiabetic medications that have recently been shown to represent favorable effects on patients’cardiorenal outcomes.However,there is shortage of data on potential disparities in this therapeutic effect across different patient subpopulations.AIM To investigate differential effects of SGLT2i on the cardiorenal outcomes of heart failure patients across left ventricular ejection fraction(LVEF)levels.METHODS Literature was searched systematically for the large randomized double-blind controlled trials with long enough follow up periods reporting cardiovascular and renal outcomes in their patients regarding heart failure status and LVEF levels.Data were then meta-analyzed after stratification of the pooled data across the LVEF strata and New York Heart Associations(NYHA)classifications for heart failure using Stata software version 17.0.RESULTS The literature search returned 13 Large clinical trials and 13 post hoc analysis reports.Meta-analysis of the effects of gliflozins on the primary composite outcome showed no significant difference in efficacy across the heart failure subtypes,but higher efficacy were detected in patient groups at lower NYHA classifications(I2=46%,P=0.02).Meta-analyses across the LVEF stratums revealed that a baseline LVEF lower than 30%was associated with enhanced improvement in the primary composite outcome compared to patients with higher LVEF levels at the borderline statistical significance(HR:0.70,95%CI:0.60 to 0.79 vs 0.81,95%CI:0.75 to 0.87;respectively,P=0.06).Composite renal outcome was improved significantly higher in patients with no heart failure than in heart failure patients with preserved ejection fraction(HFpEF)(HR:0.60,95%CI:0.49 to 0.72 vs 0.94,95%CI:0.74 to 1.13;P=0.04).Acute renal injury occurred significantly less frequently in heart failure patients with reduced ejection fraction who received gliflozins than in HFpEF(HR:0.67,95%CI:51 to 0.82 vs 0.94,95%CI:0.82 to 1.06;P=0.01).Volume depletion was consistently increased in response to SGLT2i in all the subgroups.CONCLUSION Heart failure patients with lower LVEF and lower NYHA sub-classifications were found to be generally more likely to benefit from therapy with gliflozins.Further research are required to identify patient subgroups representing the highest benefits or adverse events in response to SGLT2i.

Saudi Consensus on the Usage of Sodium-Glucose Cotransporter-2 Inhibitors on the Management of Chronic Kidney Diseases

According to recent epidemiological data, chronic kidney diseases (CKDs) affect approximately 10% of the global population. Like many countries, CKD is a significant public health issue in Saudi Arabia. The prevalence of CKD in Saudi Arabia is estimated to be around 4.5% of the adult population, with a higher prevalence in older age groups. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a class of oral medications used to treat type 2 diabetes mellitus (T2DM). In addition to their glucose-lowering effects, SGLT2i have been shown to have beneficial effects on kidney function in patients with or without T2DM. Therefore, a Saudi task force gathered to develop an explicit, evidence-based consensus on SGLT2i use in CKD Saudi patients. A panel of 14 experts made up a task force. An initial concept proposal was obtained. The proposal was divided into several topics discussed on 24 May 2023. A literature review was carried out. The literature search was completed on 3rd June 2023. A drafted report was distributed to the entire panel. Approval of the recommendations required consensus, defined as a majority approval (i.e. above 75%). The recommendations were revised to accommodate any differences of opinion until a consensus was reached. Recommendations were finally formulated on 21st June 2023. Subsequently, the panel reviewed and discussed the supporting rationale of the revised recommendations. This article presents these practical recommendations.

Role of sodium-glucose co-transporter-2 inhibitors in the management of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general population and is also more severe histologically in this group. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, the newest class of antidiabetic agents, appear to represent a promising option for the management of NAFLD in patients with T2DM. In a number of studies, treatment with SGLT2 inhibitors resulted in a reduction in hepatic steatosis and in transaminase levels. However, existing studies are small, their follow-up period was short and none evaluated the effects of SGLT2 inhibitors on liver histology. Accordingly, larger studies are needed to verify these preliminary results and define the role of SGLT2 inhibitors in the treatment of NAFLD in patients with T2DM.

Sodium-glucose cotransporter-2 inhibitor use in kidney transplant recipients

Sodium-glucose cotransporter-2 inhibitors(SGLT2i)are novel oral hypoglycemic agents garnering much attention for their substantial benefits.These recent data have positioned SGLT2i at the forefront of diabetic chronic kidney disease(CKD)and heart failure management.SGLT2i use post-kidney transplant is an emerging area of research.Highlights from this mini review include the following:Empagliflozin is the most prescribed SGLT2i in kidney transplant recipients(KTRs),median time from transplant to initiation was 3 years(range:0.88-9.6 years).Median baseline estimated glomerular filtration rate(eGFR)was 66.7 mL/min/1.73 m2(range:50.4-75.8).Median glycohemoglobin(HgbA1c)at initiation was 7.7%(range:6.9-9.3).SGLT2i were demonstrated to be effective short-term impacting HgbA1c,eGFR,hemoglobin/hematocrit,serum uric acid,and serum magnesium levels.They are shown to be safe in KTRs with low rates of infections,hypoglycemia,euglycemic diabetic ketoacidosis,and stable tacrolimus levels.More data is needed to demonstrate long-term outcomes.SGLT2i appear to be safe,effective medications for select KTRs.Our present literature,though limited,is founded on precedent robust research in CKD patients with diabetes.Concurrent research/utilization of SGLT2i is vital to not only identify long-term patient,graft and cardiovascular outcomes of these agents,but also to augment management in KTRs.

Impact of sodium glucose cotransporter-2 inhibitors on liver steatosis/fibrosis/inflammation and redox balance in non-alcoholic fatty liver disease

BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT2-I)are the most recently approved drugs for type 2 diabetes(T2D).Recent clinical trials of these compounds reported beneficial cardiovascular(CV)and renal outcomes.A major cause of vascular dysfunction and CV disease in diabetes is hyperglycemia associated with inflammation and oxidative stress.Pre-clinical studies demonstrated that SGLT2-I reduce glucotoxicity and promote anti-inflammatory effects by lowering oxidative stress.AIM To investigate the effects of SGLT2-I on markers of oxidative stress,inflammation,liver steatosis,and fibrosis in patients of T2D with non-alcoholic fatty liver disease(NAFLD).METHODS We referred fifty-two consecutive outpatients treated with metformin monotherapy and exhibiting poor glycemic control to our centre.We introduced the outpatients to an SGLT2-I(dapagliflozin,empagliflozin,or canagliflozin;n=26)or a different hypoglycemic drug[other glucose-lowering drugs(OTHER),n=26].We evaluated circulating interleukins and serum hydroxynonenal(HNE)-or malondialdehyde(MDA)-protein adducts,fatty liver index(FLI),NAFLD fibrosis score,aspartate aminotransferase(AST)/alanine aminotransferase(ALT)ratio,AST-to-platelet-ratio index(APRI),and fibrosis-4 on the day before(T0)and following treatment for six months(T1).We also performed transient elastography at T0 and T1.RESULTS Add-on therapy resulted in improved glycemic control and reduced fasting blood glucose in both groups.Of note,following treatment for six months,a reduction of FLI and APRI,as well as of the FibroScan result,was reported in patients treated with SGLT2-I,but not in the OTHER group;furthermore,in the SGLT2-I group,we reported lower circulating levels of interleukin(IL)-1β,IL-6,tumor necrosis factor,vascular endothelial growth factor,and monocyte chemoattractant protein-1,and higher levels of IL-4 and IL-10.We did not observe any modification in circulating interleukins in the OTHER group.Finally,serum HNE-and MDA-protein adducts decreased significantly in SGLT2-I rather than OTHER patients and correlated with liver steatosis and fibrosis scores.CONCLUSION The present data indicate that treatment with SGLT2-I in patients with T2D and NAFLD is associated with improvement of liver steatosis and fibrosis markers and circulating pro-inflammatory and redox status,more than optimizing glycemic control.

Sodium glucose cotransporter 2 inhibitors:New horizon of the heart failure pharmacotherapy

Sodium-glucose cotransporter 2(SGLT2)inhibitors have gained momentum as the latest class of antidiabetic agents for improving glycemic control.Large-scale clinical trials have reported that SGLT2 inhibitors reduced cardiovascular outcomes,especially hospitalization for heart failure in patients with type 2 diabetes mellitus who have high risks of cardiovascular disease.Accumulating evidence has indicated that beneficial effects can be observed regardless of the presence or absence of type 2 diabetes mellitus.Accordingly,the Food and Drug Administration approved these agents specifically for treating patients with heart failure and a reduced ejection fraction.It has been concluded that canagliflozin,dapagliflozin,empagliflozin,or ertugliflozin can be recommended for preventing hospitalization associated with heart failure in patients with type 2 diabetes and established cardiovascular disease or those at high cardiovascular risk.In the present review,we explore the available evidence on SGLT2 inhibitors in terms of the cardioprotective effects,potential mechanisms,and ongoing clinical trials that may further clarify the cardiovascular effects of the agents.

Glucagon-like-1 receptor agonists and sodium/glucose cotransporter-2 inhibitors combination—are we exploiting their full potential in a real life setting?

BACKGROUND The sodium/glucose cotransporter-2 inhibitors(SGLT-2i)and glucagon-like-1 receptor agonists(GLP-1RA)are antidiabetic agents effective both in hemoglobin A1c(HbA1c)reduction(with a low risk of hypoglycemia)and cardiovascular event prevention.In patients with type 2 diabetes,the add-on value of combination therapy of GLP-1RA and an SGLT-2i seems promising.AIM To investigate whether the efficacy of GLP-1RA and SGLT-2i combination observed in randomized controlled trials translates into therapeutic benefits in the Croatian population during routine clinical practice and follow-up.METHODS We included 200 type 2 diabetes patients with poor glycemic control and analyzed the effects of treatment intensification with(1)GLP-1RA on top of SGLT-2i,(2)SGLT-2i on top of GLP-1RA compared to(3)simultaneous addition of both agents.The primary study endpoint was the proportion of participants with HbA1c<7.0%and/or 5%bodyweight reduction.Secondary outcomes included changes in fasting plasma glucose(FPG),prandial plasma glucose,lowdensity lipoprotein cholesterol,estimated glomerular filtration rate(eGFR),and cardiovascular(CV)incidents assessment over a follow-up period of 12 mo.RESULTS The majority of patients were over 65-years-old,had diabetes duration for more than 10 years.The initial body mass index was 39.41±5.49 kg/m2 and HbA1c 8.32±1.26%.Around half of the patients in all three groups achieved target HbA1c below 7%.A more pronounced decrease in the HbA1c seen with simultaneous SGLT-2i and GLP-1RA therapy was a result of higher baseline HbA1c and not the effect of initiating combination therapy.The number of patients achieving FPG below 7.0 mmol/L was significantly higher in the SGLT-2i group(P=0.021),and 5%weight loss was dominantly achieved in the simultaneous therapy group(P=0.044).A composite outcome(reduction of HbA1c below 7%(53 mmol/mol)with 5%weight loss)was achieved in 32.3%of total patients included in the study.Only 18.2%of patients attained composite outcome defined as HbA1c below 7%(53 mmol/mol)with 5%weight loss and low-density lipoprotein cholesterol<2.5 mmol/L.There were no significant differences between treatment groups.No differences were observed regarding CV incidents or eGFR according to treatment group over a follow-up period.CONCLUSION Combination therapy with GLP-1RA and SGLT-2i is effective in terms of metabolic control,although it remains to be determined whether simultaneous or sequential intensification is better.

Sodium glucose cotransporter-2 inhibitors: Are we targeting old devil with new problems?

Dear editor,The advent of modern molecular mechanism’s approach to disease treatment is highly advancing to mitigate/normalize the symptoms of disease i.e.hyperglycemia by targeting at least eight different pathophysiological approaches popularly known as omnious octet[1].Importantly,type 2 diabetes is a

Mechanism Underlying Increase of the Serum Magnesium Concentration Observed Following Treatment with Sodium-Glucose Cotransporter 2 Inhibitors

Aim: The EMPA-REG OUTCOME study reported that the sodium-glucose cotransporter 2 inhibitor (SGLT2-i) suppressed cardiovascular (CV) events in patients with type 2 diabetes;we recently suggested that increase of the serum magnesium (Mg) by SGLT2-i’s can, in part, explain this reduction. The objective of this study was to elucidate the mechanism underlying the elevation of the serum Mg level induced by treatment with SGLT2-i’s. Methods: We analyzed the data of 37 patients with type 2 diabetes who underwent clinical evaluation and laboratory assessment at baseline and the end of 3 months. To investigate the relationship between the changes in the serum Mg concentrations during 3 months’ treatment (ΔMg) and other variables, we carried out simple linear regression analysis and multiple linear regression analysis. Results: Three months’ treatment with the SGLT2-i resulted in a significant improvement of the body weight (BW), BMI, hemoglobin A1c (HbA1c), and fasting plasma glucose levels. The serum Mg increased significantly. Simple linear regression analysis revealed an association between the ΔMg and the serum triglyceride, serum Mg at baseline, change of the BW (ΔBW), and change of the HbA1c. Multiple linear regression analysis revealed a significant association between the ΔMg and the serum Mg level at the baseline (r = -0.55, P Conclusion: Our study revealed that a lower serum Mg level at the baseline and BW reduction were significantly associated with an increase in the serum Mg following 3 months’ treatment with SGLT2-i’s.

Ipragliflozin: A novel sodium-glucose cotransporter 2 inhibitor developed in Japan

Sodium-glucose cotransporter 2(SGLT2) inhibition induces glucosuria and decreases blood glucose levels in diabetic patients and lowers hypoglycemic risk. SGLT1 is expressed in the kidney and intestine; SGLT1 inhibition causes abdominal symptoms such as diarrhea and reduces incretin secretion. Therefore, SGLT2 selectivity is important. Ipragliflozin is highly selective for SGLT2. In type 2 diabetes mellitus(T2DM), urinaryglucose excretion increased to 90 g/24 h after 28 d of treatment with ipragliflozin 300 mg/d. Twelve weeks of ipragliflozin 50 mg/d vs placebo reduced glycated hemoglobin and body weight by 0.65% and 0.66 kg, respectively, in Western T2 DM patients, and by 1.3% and 1.89 kg, respectively, in Japanese patients. Ipragliflozin(highly selective SGLT2 inhibitor) improves glycemic control and reduces body weight and lowers hypoglycemic risk and abdominal symptoms. Ipragliflozin can be a novel anti-diabetic and antiobesity agent.

Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice

BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIM To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODS The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTS Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba mice.Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin.In non-diabetic C57 BL/6 J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.CONCLUSION The inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1 D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1 D and its complications.

钠-葡萄糖协同转运蛋白2抑制剂对急性心肌梗死合并2型糖尿病患者临床指标及预后的影响

目的观察钠-葡萄糖协同转运蛋白2抑制剂(SGLT-2i)对急性心肌梗死(AMI)合并2型糖尿病(T2DM)患者临床指标及预后的影响。方法回顾性选取2020年1月至2022年6月于安徽医科大学第二附属医院胸痛中心就诊后确诊AMI合并T2DM患者180例,根据入院后降糖方案分为对照组(79例,给予磺脲类、α-糖苷酶抑制剂、二甲双胍等药物)和观察组(101例,给予达格列净或恩格列净)。患者出院后定期随访,比较2组患者临床指标及主要不良心血管事件(MACE)发生情况。结果所有患者随访6~12个月,结果显示观察组白细胞计数小于对照组[(7.4±1.6)×10^(9)/L比(8.7±1.6)×10^(9)/L],左心室舒张末期内径改善优于对照组[(-0.527±1.462)mm比(1.359±2.111)mm](均P<0.05)。观察组MACE发生率低于对照组[5.4%(2/37)比25.0%(8/32)],差异有统计学意义(P=0.020)。结论SGLT-2i较其他降糖药物12个月内能改善AMI合并T2DM患者的心脏功能及预后,且能减轻该类患者的全身炎症反应。

20例钠-葡萄糖共转运蛋白2抑制剂致福涅尔坏疽病例及文献分析

目的探讨钠-葡萄糖共转运蛋白2抑制剂(SGLT-2i)致福涅尔坏疽(FG)的发生特点,为临床安全用药提供参考。方法采用计算机检索PubMed、Embase、中国知网、万方、维普数据库自建库起至2023年6月有关SGLT-2i致FG的病例报道,并对相关数据进行统计和分析。结果共纳入20篇文献,涉及20例患者。其中,男14例(70.00%),女6例(30.00%);年龄(56.0±11.5)岁;12例(60.00%)描述为肥胖,其中5例为极重度肥胖(体质量指数不低于40 kg/m^(2))。FG发生中位时间为425 d,FG发生时糖化血红蛋白(HbA_(1C))平均值为9.2%。SGLT-2i致FG相关性为很可能的有8例,可能的有12例。20例患者经停药、及时清创引流及给予抗菌药物治疗后转归均良好。结论临床使用SGLT-2i时需注意识别其致FG的危险因素,一旦生殖器或会阴区域出现可疑的肿胀、疼痛等不适,需立即就医,并给予积极治疗。

SGLT-2抑制剂致成人2型糖尿病患者糖尿病酮症酸中毒风险的Meta分析

目的对钠—葡萄糖协同转运蛋白2(SGLT-2)抑制剂致成人2型糖尿病(T2DM)患者糖尿病酮症酸中毒(DKA)风险进行系统Meta分析。方法检索美国国立医学图书馆数据库、医学文摘数据库、Cochrane循证医学数据库从建库至2023年12月31日收录SGLT-2抑制剂治疗T2DM患者的随机对照试验。提取纳入文献的样本量、患者性别、年龄、体质量指数、发生DKA情况、治疗时间及药物种类。使用RevMan5.4版软件进行Meta分析,二分类变量以相对危险度(RR)值及95%CI作为效应量。结果最终共纳入26篇文献65176例T2DM患者,其中SGLT-2抑制剂治疗(观察组)37021例,对照组28155例;共发生DKA事件139例,观察组DKA事件发生率为0.29%(106/37021),对照组DKA事件发生率为0.12%(33/28155),观察组发生DKA风险显著高于对照组(RR=2.71,95%CI 1.84~3.97,P<0.001)。进一步亚组分析提示SGLT-2抑制剂组中年龄>60岁(RR=2.73,95%CI 1.84~4.05,P<0.001)、体质量指数≥31 kg/m^(2)(RR=2.73,95%CI 1.82~4.07,P<0.001)、治疗时间>52周(RR=2.73,95%CI 1.84~4.05,P<0.001)、使用卡格列净(RR=4.82,95%CI 1.70~13.64,P=0.003)、埃格列净(RR=4.10,95%CI 1.11~15.20,P=0.040)发生DKA风险均较对照组明显升高。结论成人T2DM患者应用SGLT-2抑制剂会增加DKA风险,且年龄越大、体质量指数越高、治疗时间越长发生DKA的风险就越高,另外DKA发生风险也与药物种类有关。

达格列净对2型糖尿病非增殖期视网膜病变的影响

目的:探讨达格列净对2型糖尿病非增殖期视网膜病变(non-proliferative diabetic retinopathy,NPDR)的影响。方法:选取2021年10月—2023年6月湖南师范大学附属湘东医院收治的88例2型糖尿病NPDR患者。随机将其分为观察组及对照组,各44例。两组均给予常规降糖治疗,观察组加用达格列净治疗。比较两组治疗前后血糖指标及相关指标。分析血管内皮生长因子(vascular endothelial growth factor,VEGF)与血糖波动指标的相关性。结果:治疗后,两组空腹血糖(fasting blood glucose,FBG)、餐后2 h血糖(2 h postprandial blood glucose,2 h PBG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、血糖水平标准差(standard deviation of blood glucose,SDBG)、餐后血糖波动幅度(postprandial glucose excursion,PPGE)、最大血糖波动幅度(large amplitude glycemic excursion,LAGE)均下降,观察组SDBG、PPGE、LAGE均低于对照组,差异有统计学意义(P<0.05)。治疗后,两组VEGF、黄斑中心凹厚度均下降,最佳矫正视力(best-corrected visual acuity,BCVA)升高,观察组VEGF、黄斑中心凹厚度均低于对照组,BCVA高于对照组,差异有统计学意义(P<0.05)。Pearson相关性分析结果显示:VEGF与SDBG、PPGE、LAGE均呈正相关(P<0.05)。结论:达格列净能够改善血糖波动,降低VEGF水平,对2型糖尿病NPDR有保护作用。

SGLT-2抑制剂达格列净治疗早期糖尿病肾病的临床效果和安全性分析

目的分析在早期糖尿病肾病治疗中采用钠-葡萄糖协同转运蛋白2(Sodium-dependent Glucose Transporters 2,SGLT-2)抑制剂达格列净的疗效和安全性。方法选取2022年3月—2023年12月北京市第六医院收治的100例早期糖尿病肾病患者为研究对象,以随机数表法分为研究组和对照组,各50例。给予全部患者常规治疗,研究组加用达格列净治疗,对照组加用二甲双胍治疗,对比两组血糖水平、肾功能和不良反应发生情况。结果治疗后,研究组空腹血糖为(5.16±0.77)mmol/L,餐后2 h血糖为(7.11±1.38)mmol/L,糖化血红蛋白为(5.05±0.73)%,低于对照组,差异有统计学意义(t=4.592、5.020、5.093,P均<0.05)。治疗后,研究组尿白蛋白/肌酐比值、肾小球过滤率优于对照组,差异有统计学意义(P均<0.05)。研究组不良反应发生率低于对照组,差异有统计学意义(P<0.05)。结论在早期糖尿病肾病治疗中采用SGLT-2抑制剂达格列净疗效显著,可以有效降低血糖水平,改善肾功能,降低不良反应发生率。

钠-葡萄糖共转运蛋白2抑制剂对急性心肌梗死合并2型糖尿病患者的安全性及有效性评价

目的:探究钠-葡萄糖共转运蛋白2抑制剂(sodium-glucose co-transporter-2 inhibitor,SGLT2i)对合并2型糖尿病(type 2 diabetes mellitus,T2DM)的急性心肌梗死(acute myocardial infarction,AMI)患者的疗效及安全性。方法:研究纳入2018年1月至2023年1月,在首都医科大学附属北京安贞医院行PCI手术且合并T2DM的AMI患者共2 170例,其中357例患者使用SGLT2i,并根据患者出院带药是否使用SGLT2i分成两组:SGLT2i组和常规降糖组,通过倾向性匹配法进行1:1匹配。本研究主要有效性终点事件为支架术后12个月内心血管不良事件(major adverse cardiovascular events,MACE),包含全因死亡、非致命心肌梗死、或缺血相关血运重建,主要安全终点事件为严重出血事件。结果:通过倾向评分匹配成功357对,两组患者基线特征基本一致,差异无统计学意义。研究平均随访(11.7±1.4)个月。与常规降糖组相比,达格列净组的主要有效性终点事件(HR=0.47,95%CI 0.27~0.81,P=0.006)以及次要终点事件中缺血相关血运重建(HR=0.53,95%CI:0.30~0.93,P=0.026)的发生率较低。两组的主要安全性终点事件(HR=0.72,95%CI:0.29~1.81,P=0.492)、全因死亡(HR=0.49,95%CI:0.23~1.06,P=0.069)和心肌梗死(HR=0.62,95%CI:0.32~1.18,P=0.142)发生率差异未见统计学意义。结论:SGLT2i可以降低合并2型糖尿病的急性心肌梗死患者的MACE、心肌梗死或缺血相关血运重建发生率,同时并不增加安全事件风险。

钠-葡萄糖共转运蛋白2抑制剂对射血分数保留心力衰竭中冠状动脉微血管功能障碍的影响

射血分数保留的心力衰竭(heart failure with preserved ejection fraction,HFp EF)约占心力衰竭的50%,且呈增长趋势。HFp EF的发病机制目前仍不完全清楚,临床上缺乏有效的治疗方法。近年来的研究证据表明,冠状动脉微血管功能障碍在HFp EF的发生发展中发挥关键作用。钠-葡萄糖共转运蛋白2 (sodium-dependent glucose transporters 2,SGLT2)抑制剂显著改善射血分数减低的心力衰竭(heart failure with reduced ejection fraction,HFrEF)患者的临床预后且独立于血糖控制,其已被推荐为HFrEF患者的基础治疗药物。SGLT2抑制剂具有广泛的生物学功能。SGLT2抑制剂通过抑制炎症和氧化应激、减轻胰岛素抵抗、维持内皮功能等作用改善冠状动脉微血管功能。目前,尽管仍缺少足够的循证医学证据,SGLT2抑制剂仍被认为是治疗HFpEF的理想方案。