中国成人2型糖尿病患者糖化血红蛋白控制目标及达标策略专家共识

糖化血红蛋白(HbA1C)控制目标应遵循患者为中心的个体化原则,即根据患者的年龄、病程、健康状况、药物不良反应风险等因素实施分层管理。本共识建议一般成人2型糖尿病(T2DM)患者的HbA1C控制目标为<7.0%,并对其他情况下的HbA1C目标值作出推荐。本共识建议将二甲双胍作为T2DM患者单药治疗的首选,α-糖苷酶抑制剂(AGI)或胰岛素促泌剂作为单药治疗的备选。进行联合治疗时,建议根据患者是否合并动脉粥样硬化性心血管疾病(ASCVD)、心力衰竭(HF)或慢性肾脏疾病(CKD)进行分层。如患者合并ASCVD,建议在具备条件的情况下联合有心血管获益证据的胰升糖素样肽-1受体激动剂(GLP-1RA)或钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)。如患者合并CKD,建议联合用药时在条件允许的情况下首选有肾脏获益证据的SGLT2i,在患者不能使用SGLT2i时可选择有肾脏获益证据的GLP-1RA。如患者合并HF,建议在条件允许时选择SGLT2i。如患者未合并ASCVD、HF或CKD时,可根据基线HbA1C水平、低血糖风险、体重、经济状况、药物可及性等因素选择联合的药物。     

钠-葡萄糖共转运蛋白2抑制剂抗氧化应激防治糖尿病肾脏疾病的研究进展

DKD是终末期肾病的首要原因。钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)除有效降糖外,还可使合并慢性肾脏疾病、心脑血管疾病及心力衰竭的T2DM患者获益。SGLT2i通过肾脏排糖、排钠延缓DKD进展。SGLT2i可通过降低BP、UA、减轻体重、改善肾脏血流动力、减轻内质网应激及激活缺氧诱导因子通路等实现肾脏保护作用。氧化应激在DKD发生发展中起重要作用。本文对SGLT2i通过抗氧化应激防治DKD的研究进展进行综述。     

SGLT2抑制剂治疗2型糖尿病合并心力衰竭的疗效和安全性的Meta分析

目的 系统评价钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)治疗2型糖尿病(T2DM)合并心力衰竭(心衰,HF)的有效性和安全性.方法 系统检索了CocHRane图书馆、Web of science、PubMed、Embase数据库,检索时限均为建库起至2020年11月20日,搜索了SGLT2i对比安慰剂治疗T2DM合并...     

钠-葡萄糖共转运蛋白2抑制剂的临床应用:始于降糖超越降糖北大核心CSCD

钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)是一类近年来受高度重视的新型口服降糖药,以肾脏近曲小管SGLT2为作用靶点,降低肾糖阈,促进尿糖排出,从而实现降糖作用。SGLT2i不仅具有不依赖胰岛素的独特降糖作用,还有超越降糖外的获益,如减轻体重、降低血压、调节血脂、降低尿酸、改善代谢相关脂肪性肝病(MAFLD)。更重要的是,SGLT2i能显著减少2型糖尿病(T2DM)患者心血管疾病终点事件,对伴或不伴T2DM的患者心衰和慢性肾脏病均具有保护作用,在T2DM的综合管理中发挥重要作用。     

改善心血管和肾脏结局的新型抗高血糖药物临床应用中国专家建议

动脉粥样硬化性心血管病(ASCVD)和(或)慢性肾脏病(CKD)不但是2型糖尿病(T2DM)常见合并疾病,也是T2DM患者致残和致死的首要原因。近年来一系列临床研究证据表明,新型抗高血糖药物胰高糖素样肽-1受体激动剂(GLP-1 RA)和钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)类药物能显著改善心血管和肾脏结局的临床获益,且安全性良好。为促使T2DM的治疗模式从单纯控制血糖转移到改善心血管和肾脏临床结局,中国心血管病学、内分泌学、肾脏病学和神经病学专家组成的专家组梳理了GLP-1 RA或SGLT2i的心血管保护的临床证据、可能机制和常见不良反应,提出了对这两类药物在临床实践中的合理定位、应用建议和注意事项,鼓励临床医师在临床实践中对T2DM患者及早启动并长期维持能够改善心血管和肾脏结局的新型抗高血糖药物治疗。     

SGLT2抑制剂对2型糖尿病患者心血管保护作用研究的进展

心血管疾病(CVD)是2型糖尿病(T2DM)患者的首要死因。钠-葡萄糖转运体2(SGLT2)抑制剂是一种新近使用的降糖药,大量研究表明其对于T2DM患者的心血管具有保护作用。但其中涉及的机制尚未探明。在应用SGLT2抑制剂时,应利用其保护心血管作用的优势,也应警惕其不良反应。本文汇总了近年SGLT2抑制剂对T2DM患者心血管获益有关的临床研究,以期为T2DM合并CVD患者的治疗提供新思路。     

SGLT2抑制剂和GLP-1受体激动剂对2型糖尿病患者心血管保护作用研究进展

大量研究表明钠-葡萄糖共转运体2(SGLT2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(GLP-1RA)在降低2型糖尿病(T2DM)患者的死亡率和心血管风险方面显示出积极的效果。本文综述了SGLT2抑制剂和GLP-1RA对T2DM患者心血管获益有关的临床研究。以期针对T2DM合并心血管疾病患者的不同临床受益情况，提供个体化用药选择思路。     

钠-葡萄糖协同转运蛋白2抑制剂对2型糖尿病合并心房颤动影响的研究进展

心房颤动(AF)是临床常见心律失常,显著增加脑卒中、心力衰竭等风险,严重危害人类健康.T2DM是常见慢性疾病之一,可增加AF风险,与AF患者心血管死亡风险增加相关.T2DM合并AF的病理生理机制尚不明确,可能与心房电、结构及自主神经重构相关.SGLT2i是一种新型降糖药,除有显著降糖效果外,还降低T2DM患者AF风险....     

钠-葡萄糖共转运蛋白2抑制剂心血管获益机制研究进展

近年来,新型口服降糖药物钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）在2型糖尿病患者心血管获益方面涌现出大量证据,多项临床试验显示SGLT2i可以显著降低2型糖尿病患者心血管死亡风险,并减少心力衰竭住院率,其中达格列净被证实对非糖尿病的心力衰竭患者同样具有心血管保护作用。目前针对SGLT2i心血管获益具体机制方面的研究已取得部分进展,本文将从容量调节学说、改善血管内皮功能、改善心脏能量代谢、改善心室重构和调节全身代谢 5个方面阐述SGLT2i心血管获益的机制。     

钠葡萄糖协同转运体2抑制剂辅助治疗1型糖尿病患者发生酮症酸中毒的研究进展

终生外源性胰岛素替代治疗是1型糖尿病(T1DM)的主要治疗方法，绝大多数非胰岛素的降糖药物不适用于T1DM。钠葡萄糖协同转运体2抑制剂(SGLT2i)通过阻断肾脏近端小管的钠葡萄糖协同转运体2(SGLT2)来抑制葡萄糖的重吸收，目前广泛应用于2型糖尿病(T2DM)的治疗。临床研究表明SGLT2i能有效控制T1DM患者的血糖，但具有增加酮症酸中毒(DKA)的风险，其中非高血糖性DKA(euDKA)是SGLT2i所致DKA的常见形式。SGLT2i导致DKA的主要机制为大量排出尿糖以降低血糖，从而降低胰岛素、升高胰高血糖素水平，导致胰岛素和胰高血糖素比例失衡，胰高血糖素可促进肝细胞对脂肪的分解及脂肪酸的氧化，从而刺激肝脏生酮。T2DM患者在应用SGLT2i的情况下发生euDKA,需要警惕T1DM的可能。为避免DKA的发生，挑选合适的患者、慎重降低胰岛素用量、降低SGLT2i剂量、定期监测酮体变化、避免诱因及补充液体可能是合理的方法。SGLT2i适当增加酮体可能对心血管、肾脏及大脑有益。     

When and How to Use Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Heart Failure With Reduced Ejection Fraction or Chronic Kidney Disease

The role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in preventing heart failure (HF) in people with type 2 diabetes (T2DM) is now part of current treatment recommendations. Two large clinical trials (DAPA-HF and EMPEROR-Reduced) have recently highlighted the important impact of SGLT2 inhibitors in patients with HF and a reduced ejection fraction (HFrEF), with significant outcome benefits on HF hospitalisations and cardiovascular mortality, and similar effects in patients with and without T2DM. These benefits were observed on top of excellent background HF therapy, and there were no treatment interactions between SGLT2 inhibitors and background HF therapy. There were no increases in adverse events of interest in the SGLT2 inhibitor arm, including volume depletion, adverse renal events, hypoglycemia, amputation, and ketoacidosis, demonstrating the favourable safety profile of this treatment in HFrEF. Approximately 40%-50% of patients with HFrEF have chronic kidney disease (CKD), and the recently reported results of the DAPA-CKD trial indicate that dapagliflozin can prevent renal and cardiovascular outcomes in patients with established CKD, whether diabetes is present or not. Although the mechanisms of action of SGLT2 inhibitors are not fully understood, the hypotheses that have been proposed for their HF outcome benefits include a reduction of preload via osmotic diuresis, lowering of afterload, reduction in myocardial mass, alteration of myocardial energy substrate toward a more efficient glucose metabolism, modulation of renal sympathetic afferent tone, and increased erythropoiesis. We here present a summary of the evidence as well as a practical perspective on prescribing SGLT2 inhibitors in patients with HFrEF, with or without diabetes.     

European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose‐lowering drugs in patients with heart failure

Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and associated with considerable morbidity and mortality. Significant advances have recently occurred in the treatment of T2DM, with evidence of several new glucose‐lowering medications showing either neutral or beneficial cardiovascular effects. However, some of these agents have safety characteristics with strong practical implications in HF [i.e. dipeptidyl peptidase‐4 (DPP‐4) inhibitors, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA), and sodium–glucose co‐transporter type 2 (SGLT‐2) inhibitors]. Regarding safety of DPP‐4 inhibitors, saxagliptin is not recommended in HF because of a greater risk of HF hospitalisation. There is no compelling evidence of excess HF risk with the other DPP‐4 inhibitors. GLP‐1 RAs have an overall neutral effect on HF outcomes. However, a signal of harm suggested in two small trials of liraglutide in patients with reduced ejection fraction indicates that their role remains to be defined in established HF. SGLT‐2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) have shown a consistent reduction in the risk of HF hospitalisation regardless of baseline cardiovascular risk or history of HF. Accordingly, SGLT‐2 inhibitors could be recommended to prevent HF hospitalisation in patients with T2DM and established cardiovascular disease or with multiple risk factors. The recently completed trial with dapagliflozin has shown a significant reduction in cardiovascular mortality and HF events in patients with HF and reduced ejection fraction, with or without T2DM. Several ongoing trials will assess whether the results observed with dapagliflozin could be extended to other SGLT‐2 inhibitors in the treatment of HF, with either preserved or reduced ejection fraction, regardless of the presence of T2DM. This position paper aims to summarise relevant clinical trial evidence concerning the role and safety of new glucose‐lowering therapies in patients with HF.     

Management of heart failure and type 2 diabetes mellitus: Maximizing complementary drug therapy

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease and occurs in ~25% of patients with heart failure (HF). Patients with co-morbid HF and T2DM are at elevated risk of adverse outcomes, making optimization of complementary drug therapies essential. While research is ongoing, recent advances in drug therapy, including the introduction of sacubitril/valsartan for HF with reduced ejection fraction and the finding of positive cardiovascular effects of glucose-lowering agents (particularly sodium-glucose co-transporter-2 [SGLT2] inhibitors) have the potential to transform pharmacologic management of co-morbid HF and T2DM. In this review, we provide a comprehensive overview of cardiovascular clinical trials of therapies for HF and diabetes mellitus to date and identify areas requiring further investigation. We also discuss the pathophysiologic overlap of the two diseases and explore the complementary therapeutic effects of HF and T2DM drugs, with a particular focus on sacubitril/valsartan and SGLT2 inhibitors.     

The Role of SGLT-2 Inhibitors as Part of Optimal Medical Therapy in Improving Cardiovascular Outcomes in Patients with Diabetes and Coronary Artery Disease

The optimal treatment approach to patients with coronary artery disease (CAD), including those with type 2 diabetes mellitus (T2DM), has been extensively evaluated. Several trials of stable ischemic heart disease including patients with T2DM have demonstrated that medical management is comparable to revascularization in terms of mortality and rates of major adverse cardiovascular events (MACE). There has been a growing appreciation for optimal medical therapy’s (OMT) role in improving clinical outcomes. It is vital to target T2DM patients to prevent or delay MACE events through advanced OMT, ultimately delaying if not avoiding the need for revascularization. There has been significant evolution in the development of pharmacologic management of T2DM patients. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a new pharmacologic therapy with tremendous potential to alter clinical practice and influence practice guidelines. SGLT2-inhibitors have great potential in reducing MACE in patients with T2DM and CAD. Empagliflozin should be considered as a part of OMT among these patients. If results similar to the EMPA-REG OUTCOMES trial are replicated in other trials, the use of these pharmacologic agents as a part of OMT may narrow the gap between revascularization and OMT alone in patients with T2DM and multi-vessel disease. Future studies on the role of SLGT-2 inhibitors with regard to heart failure outcomes are needed to elucidate the mechanisms and clinical effects in this vulnerable population.     

Are SGLT2 inhibitors joining the mainstream therapy for diabetes type 2?

BackgroundConventional therapies to prevent type 2 diabetes mellitus (T2DM) complications are only partially effective. Therefore, new therapeutic approaches leading to additional risk reduction are required. While many anti-diabetic medications have been prescribed world-wide for controlling T2DM over the past half-century, sodium-glucose co-transporter-2 (SGLT2) inhibitors are relatively new. In addition to their plasma glucose lowering effect, SGLT2 inhibitors have been shown to reduce considerably cardiovascular mortality rate in patients with T2DM.AimSince, a risk and benefit analysis of co-administration of SGLT2 inhibitors and other anti-diabetic agents in patients who suffer from hypertension, heart failure or renal deficiency is currently lacking, the main objective of this article is to review the recent literature and provide the health care professionals with evidence-based opinions on the subject.ConclusionSGLT2 inhibitors have relatively safe profiles and can efficiently decrease HbA1c as well as fasting and postprandial glucose levels. Furthermore, SGLT2 inhibitors administrations are not associated with significant hypoglycemic episodes or weight gain. Thus, combination of SGLT2 inhibitors and other less harmful anti-diabetic medicines could be considered if there is no any contraindication.     

Cardiovascular protection with sodium-glucose co-transporter-2 inhibitors in type 2 diabetes: Does it apply to all patients?

Patients with type 2 diabetes (T2D) are at an increased risk of cardiovascular disease (CVD). Cardiovascular risk in these patients should be considered as a continuum, and comprehensive treatment strategies should aim to target multiple disease risk factors. Large-scale clinical trials of sodium-glucose co-transporter-2 (SGLT2) inhibitors have shown an impact on cardiovascular outcomes, including heart failure hospitalization and cardiovascular death, which appears to be independent of their glucose-lowering efficacy. Reductions in major cardiovascular events appear to be greatest in patients with established CVD, particularly those with prior myocardial infarction, but are independent of heart failure or renal risk. Most large-scale trials of SGLT2 inhibitors predominantly include patients with T2D with pre-existing CVD and high cardiovascular risk at baseline, limiting their applicability to patients typically observed in clinical practice. Real-world evidence from observational studies suggests that there might also be beneficial effects of SGLT2 inhibitors on heart failure hospitalization and all-cause mortality in various cohorts of lower risk patients. The most common adverse events reported in clinical and observational studies are genital infections; however, the overall risk of these events appears to be low and easily managed. Similar safety profiles have been reported for elderly and younger patients. There is still some debate regarding the safety of canagliflozin in patients at high risk of fracture and amputation. Outstanding questions include specific patterns of cardiovascular protection according to baseline risk.     

Impact of demographic characteristics and antihyperglycemic and cardiovascular drugs on the cardiorenal benefits of SGLT2 inhibitors in patients with type 2 diabetes mellitus: A protocol for systematic review and meta-analysis

Background:It is unclear whether demographic characteristics and baseline use of hypoglycemic and cardiovascular drugs significantly affect the efficacy of sodium-glucose transporter 2 (SGLT2) inhibitors on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM).Methods:Randomized trials assessing the efficacy of SGLT2 inhibitors on cardiorenal outcomes in adult patients with T2DM were included in analysis. Three endpoints of interest were major adverse cardiovascular events (MACE), hospitalization for heart failure or cardiovascular death (HHF or CV death), and kidney composite outcome (KCO). We performed random-effects meta-analysis using the aggregate data of hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses were done according to 17 factors of interest, including 7 factors related to demographic characteristics and 10 related to baseline use of antihyperglycemic and cardiovascular drugs such as renin–angiotensin system (RAS) inhibitor. We conducted meta-regression analyses to calculate P values for subgroup differences.Results:Seven trials were included in this meta-analysis. Compared with placebo, SGLT2 inhibitors significantly lowered the risk of MACE (HR 0.90, 95% CI 0.84–0.97) regardless of demographic characteristics and baseline use of insulin, statin or ezetimibe, RAS inhibitor, beta-blocker, and diuretic (P_subgroup from 0.088–0.981); that of HHF or CV death (HR 0.78, 95% CI 0.71–0.85) regardless of demographic characteristics and baseline use of 10 antihyperglycemic and cardiovascular drugs (P_subgroup from 0.147–0.999); and that of KCO (HR 0.63, 95% CI 0.57–0.69) regardless of demographic characteristics and baseline use of statin or ezetimibe, RAS inhibitor, and diuretic (P_subgroup from 0.073–0.918).Conclusions:The cardiorenal benefits of SGLT2 inhibitors were consistent in a broad population of T2DM patients. The findings of this meta-analysis suggest that SGLT2 inhibitors should be recommended in T2DM patients for the prevention of cardiorenal events, regardless of various demographic characteristics and baseline use of various hypoglycemic and cardiovascular drugs.     

The cardiovascular outcomes,heart failure and kidney disease trials tell that the time to use Sodium Glucose Cotransporter 2 inhibitors is now

Sodium glucose contrasporter 2 inhibitors (SGLT2i) were initially introduced as a novel class of modestly effective antiglycemics. Over the last 5 years, multiple members of this class have been examined for their cardiovascular safety, effects on heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) in diverse populations with or without diabetes type 2. The plethora of studies and outcomes examined make it difficult for the practitioner to track the entirety of the evidence. SGLT2i improve cardiorenal outcomes and have a beneficial risk benefit ratio across populations with cardiovascular disease, HFrEF and kidney disease. In this quantitative review, we synthesize the data from the large outcomes trials about the benefits and risks of SGLT2i. SGLT2i reduce all cause, cardiovascular mortality, heart failure hospitalizations, need for dialysis and acute kidney injury as a class effect across a broad range of populations with diabetes Type 2 at risk for cardiovascular disease, patients with HFrEF or CKD with or without diabetes. While certain adverse events for example, diabetic ketoacidosis and genital mycotic infections are reproducibly increased by SGLT2i, the absolute increase in the risk of these complications is smaller than the absolute risk reductions conferred by SGLT2i. Other complications such as amputations, fractures and urinary tract infections are increased to a lesser degree, or not at all (e.g., hypoglycemia). Overall, SGLT2is appear to have a favorable safety profile and thus should be used by cardiologists, nephrologists, endocrinologists, primary care physicians when managing the cardiorenal risk of their patients.     

A complete review of empagliflozin: Most specific and potent SGLT2 inhibitor used for the treatment of type 2 diabetes mellitus

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the latest class of drugs to be introduced for the treatment of type 2 diabetes mellitus (T2DM). They reduce hyperglycemia by increasing urinary glucose excretion and exert favorable effects beyond glucose control with consistent body weight, blood pressure, and serum uric acid reductions.Empagliflozin is a potent SGLT2 inhibitor used to improve glycemic control in adults with T2DM. It has the highest SGLT2 specificity among all the clinically used or currently tested SGLT2 inhibitors. Low risk of hypoglycemia, absence of weight gain and demonstrated cardiovascular risk reduction support its consideration as a first line medication in addition to metformin for patients with T2DM and cardiovascular disease. Mostly reported adverse events are genital mycotic infections, while urinary tract infections and events linked to volume depletion are rather rare. This review covers the complete information on empagliflozin including the history of its development, synthesis, pharmacology and different methods which have been reported for its analysis.