With notable Reno protective advantages beyond glycemic management,sodiumglucose cotransporter-2(SGLT2)inhibitors have become a mainstay treatment for type 2 diabetes mellitus and chronic kidney disease(CKD).Although ...With notable Reno protective advantages beyond glycemic management,sodiumglucose cotransporter-2(SGLT2)inhibitors have become a mainstay treatment for type 2 diabetes mellitus and chronic kidney disease(CKD).Although SGLT2 inhibitors'involvement in the course of CKD has been well investigated,new research indicates that they may also have protective benefits in acute kidney injury(AKI),a condition for which there are few pharmacological treatments.The possible ways that SGLT2 inhibitors aid in AKI recovery are examined in this mini-review.These include mitochondrial protection,oxidative stress attenuation,anti-inflammatory effects,intraglomerular pressure decrease,and modulation of tubuloglomerular feedback.Although there is a lack of solid clinical trial data,preclinical models and observational studies suggest that SGLT2 inhibitors may lessen ischemia-reperfusion injury and contrast-induced nephropathy.This review addresses the possibility of incorporating SGLT2 inhibitors into AKI care regimens,critically evaluates the available data,and highlights important research gaps.Robust clinical trials are required to determine the safety,effectiveness,and ideal treatment window of SGLT2 inhibitors in this context,given the burden of AKI-related morbidity and mortality.展开更多
AIM:To investigate the effects of dipeptidyl peptidase-4 inhibitors(DPP4i)and sodium-glucose cotransporter-2 inhibitors(SGLT2i)on diabetic macular edema(DME)and the need for intravitreal injections(IVT)in patients wit...AIM:To investigate the effects of dipeptidyl peptidase-4 inhibitors(DPP4i)and sodium-glucose cotransporter-2 inhibitors(SGLT2i)on diabetic macular edema(DME)and the need for intravitreal injections(IVT)in patients with type 2 diabetes.METHODS:Data were retrospectively collected from the medical records of patients with diabetic retinopathy(DR)taking either DPP4i or SGLT2i as secondary oral hypoglycemic agents in addition to metformin between January 2019 and July 2022.We compared the prevalence of DME and the need for IVT among patients treated with DPP4i or SGLT2i.Propensity score matching was performed using the following variables:age,duration of diabetes,blood glucose control(HbA1c)level,and severity of DR.RESULTS:A total of 268 patients with DR were included in this study.More DPP4i users needed IVT than SGLT2i users(35.3%vs 18.0%,P=0.011),while the prevalence of DME was not different.The use of SGLT2i was associated with a lower need for IVT than DPP4i[odds ratio(OR)0.404,95%confidence interval(CI)0.198-0.823],and similar trends were observed after propensity score matching(OR 0.419,95%CI 0.181-0.970).However,this tendency was not significant in multiple logistic regressions.For DME,the use of DPP4i was not a significant risk factor compared to SGLT2i.CONCLUSION:The use of SGLT2i may be associated with a lower need for IVT for overall DR complications,while other factors may contribute to this effect.The effect of SGLT2i on the prevention of DME is not evident.展开更多
BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose c...BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose cotransporter-2 inhibitor(SGLT2i)and/or glucagon like peptide-1 receptor agonists(GLP-1RAs)for renal protection.The real-world efficacy of the two medications on the urinary albumin-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR)remains to be explored.AIM To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.METHODS A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months.Propensity score matching was performed,and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio.Blood glucose,body weight,UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.RESULTS A total of 139(2.54%)patients started GLP-1RA,and 387(7.06%)received SGLT2i.After 6 months,the variations in fasting blood glucose,prandial blood glucose,and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different.UACR showed a tendency toward a greater reduction compared with the control group,although this difference was not statistically significant(GLP-1RA vs control,-2.20 vs 30.16 mg/g,P=0.812;SGLT2i vs control,-20.61 vs 12.01 mg/g,P=0.327);eGFR alteration also showed no significant differences.Significant weight loss was observed in the GLP-1RA group compared with the control group(GLP-1RA vs control,-0.90 vs 0.27 kg,P<0.001),as well as in the SGLT2i group(SGLT2i vs control,-0.59 vs-0.03 kg,P=0.010).CONCLUSION Compared with patients who received other glucose-lowering drugs,patients receiving SGLT2i or GLP-1RAs presented significant weight loss,a decreasing trend in UACR and comparable glucose-lowering effects in realworld settings.展开更多
Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequentl...Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequently augmenting urinary glucose excretion and attenuating blood glucose levels.Extensive clinical investigations have demonstrated their profound cardiovascular efficacy.Parallel basic science research has elucidated the mechanistic pathways through which diverse SGLT-2 inhibitors beneficially modulate pulmonary vascular cells and arterial remodeling.Specifically,these inhibitors exhibit promising potential in enhancing pulmonary vascular endothelial cell function,suppressing pulmonary smooth muscle cell proliferation and migration,reversing pulmonary arterial remodeling,and maintaining hemodynamic equilibrium.This comprehensive review synthesizes current literature to delineate the mechanisms by which SGLT-2 inhibitors enhance pulmonary vascular cell function and reverse pulmonary remodeling,thereby offering novel therapeutic perspectives for pulmonary vascular diseases.展开更多
BACKGROUND Sodium-glucose cotransporter-2 inhibitors(SGLT2i)are commonly prescribed to manage patients with diabetes mellitus.These agents may rarely lead to the development of euglycemic diabetic ketoacidosis(EDKA),w...BACKGROUND Sodium-glucose cotransporter-2 inhibitors(SGLT2i)are commonly prescribed to manage patients with diabetes mellitus.These agents may rarely lead to the development of euglycemic diabetic ketoacidosis(EDKA),which may complicate the disease course of these patients.AIM To analyze the demographic profile,predisposing factors,symptomology,clinical interventions and outcomes of patients presenting with EDKA secondary to SGLT2i use by reviewing the published case reports and series.METHODS We performed a systematic search of PubMed,Science Direct,Google Scholar and Reference Citation Analysis databases using the terms“canagliflozin”OR“empagliflozin”OR“dapagliflozin”OR“SGLT2 inhibitors”OR“Sodium-glucose cotransporter-2”AND“euglycemia”OR“euglycemic diabetic ketoacidosis”OR“metabolic acidosis”.The inclusion criteria were:(1)Case reports or case series with individual patient details;and(2)Reported EDKA secondary to SGLT2i.Furthermore,the data were filtered from the literature published in the English language and on adults(>18 years).We excluded:(1)Conference abstracts;and(2)Case reports or series which did not have individual biochemical data.All the case reports and case series were evaluated.The data extracted included patient demographics,clinical symptomatology,clinical interventions,intensive care unit course,need for organ support and outcomes.RESULTS Overall,108 case reports and 17 cases series with 169 unique patients that met all the inclusion criteria were included.The majority of patients were females(54.4%,n=92),and the commonly reported symptoms were gastrointestinal(nausea/vomiting 65.1%,abdominal pain 37.3%)and respiratory(breathlessness 30.8%).One hundred and forty-nine(88.2%)patients had underlying type II diabetes,and the most commonly involved SGLT-2 inhibitor reported was empagliflozin(46.8%).A triggering factor was reported in most patients(78.7%),the commonest being acute severe infection(37.9%),which included patients with sepsis,coronavirus disease 2019,other viral illnesses,and acute pancreatitis.61.5%were reported to require intensive unit care,but only a minority of patients required organ support in the form of invasive mechanical ventilation(13%),vasopressors(6.5%)or renal replacement therapy(5.9%).The overall mortality rate was only 2.4%.CONCLUSION Patients on SGLT2i may rarely develop EDKA,especially in the presence of certain predisposing factors,including severe acute infections and following major surgery.The signs and symptoms of EDKA may be similar to that of DKA but with normal blood sugar levels,which may make the diagnosis challenging.Outcomes of EDKA are good if recognized early and corrective actions are taken.Hence,physicians managing such patients must be aware of this potential complication and must educate their patients accordingly to ensure early diagnosis and management.展开更多
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...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.展开更多
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 outc...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.展开更多
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(RCT...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.展开更多
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)a...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.展开更多
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 pathophys...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展开更多
Sodium-glucose cotransporter-2(SGLT2)inhibitors have emerged as a pivotal intervention in diabetes management,offering significant cardiovascular benefits.Empagliflozin,in particular,has demonstrated cardioprotective ...Sodium-glucose cotransporter-2(SGLT2)inhibitors have emerged as a pivotal intervention in diabetes management,offering significant cardiovascular benefits.Empagliflozin,in particular,has demonstrated cardioprotective effects beyond its glucose-lowering action,reducing heart failure hospitalizations and improving cardiac function.Of note,the cardioprotective mechanisms appear to be independent of glucose lowering,possibly mediated through several mechanisms involving shifts in cardiac metabolism and anti-fibrotic,anti-inflammatory,and anti-oxidative pathways.This editorial summarizes the multifaceted cardiovascular advantages of SGLT2 inhibitors,highlighting the need for further research to elucidate their full therapeutic potential in cardiac care.展开更多
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...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 3<sup>rd</sup> 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 21<sup>st</sup> June 2023. Subsequently, the panel reviewed and discussed the supporting rationale of the revised recommendations. This article presents these practical recommendations.展开更多
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 gluco...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.展开更多
Mitochondrial dysfunction is a key driver of cardiovascular disease(CVD)in metabolic syndrome and diabetes.This dysfunction promotes the production of reactive oxygen species(ROS),which cause oxidative stress and infl...Mitochondrial dysfunction is a key driver of cardiovascular disease(CVD)in metabolic syndrome and diabetes.This dysfunction promotes the production of reactive oxygen species(ROS),which cause oxidative stress and inflammation.Angiotensin II,the main mediator of the renin-angiotensin-aldosterone system,also contributes to CVD by promoting ROS production.Reduced activity of sirtuins(SIRTs),a family of proteins that regulate cellular metabolism,also worsens oxidative stress.Reduction of energy production by mitochondria is a common feature of all metabolic disorders.High SIRT levels and 5’adenosine monophosphate-activated protein kinase signaling stimulate hypoxia-inducible factor 1 beta,which promotes ketosis.Ketosis,in turn,increases autophagy and mitophagy,processes that clear cells of debris and protect against damage.Sodiumglucose cotransporter-2 inhibitors(SGLT2i),a class of drugs used to treat type 2 diabetes,have a beneficial effect on these mechanisms.Randomized clinical trials have shown that SGLT2i improves cardiac function and reduces the rate of cardiovascular and renal events.SGLT2i also increase mitochondrial efficiency,reduce oxidative stress and inflammation,and strengthen tissues.These findings suggest that SGLT2i hold great potential for the treatment of CVD.Furthermore,they are proposed as anti-aging drugs;however,rigorous research is needed to validate these preliminary findings.展开更多
BACKGROUND Landmark trials have established the benefits of sodium-glucose cotransporter-2 inhibitors(SGLT2-Is)in cardiovascular disease including heart failure with reduced and preserved ejection fraction and renal d...BACKGROUND Landmark trials have established the benefits of sodium-glucose cotransporter-2 inhibitors(SGLT2-Is)in cardiovascular disease including heart failure with reduced and preserved ejection fraction and renal diseases regardless of the presence of diabetes mellitus.However,studies evaluating the role of SGLT2-Is in metabolic syndrome(MetS)are limited.AIM This study primarily aimed to evaluate the impact of SGLT2-Is on the components of MetS.METHODS Two independent reviewers and an experienced librarian searched Medline,Scopus and the Cochrane central from inception to December 9,2021 to identify placebo controlled randomized controlled trials that evaluated the impact of SGLT2-Is on the components of MetS as an endpoint.Pre-and post-treatment data of each component were obtained.A meta-analysis was performed using the RevMan(version 5.3;Copenhagen:The Nordic Cochrane Center,The Cochrane Collaboration).RESULTS Treatment with SGLT2-Is resulted in a decrease in fasting plasma glucose(–18.07 mg/dL;95%CI:-25.32 to–10.82),systolic blood pressure(–1.37 mmHg;95%CI:-2.08 to–0.65),and waist circumference(–1.28 cm;95%CI:-1.39 to–1.18)compared to placebo.The impact on highdensity lipoprotein cholesterol was similar to placebo(0.01 mg/dL;95%CI:-0.05 to 0.07).CONCLUSION SGLT2-Is have a promising role in the management of MetS.展开更多
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...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.展开更多
BACKGROUND Diabetic ketoacidosis(DKA)manifests as hyperglycemia,metabolic acidosis,and ketosis.However,euglycemic DKA(eu-DKA)conceals severe DKA with glucose levels below 200 mg/dL.Sodium-glucose cotransporter-2(SGLT2...BACKGROUND Diabetic ketoacidosis(DKA)manifests as hyperglycemia,metabolic acidosis,and ketosis.However,euglycemic DKA(eu-DKA)conceals severe DKA with glucose levels below 200 mg/dL.Sodium-glucose cotransporter-2(SGLT2)inhibitors can induce eu-DKA in diabetic patients.Notably,coronavirus disease 2019(COVID-19)-infected individuals with diabetes using SGLT2 inhibitors face an augmented risk of eu-DKA due to the direct toxic impact of the virus on pancreatic islets.This study aims to comprehensively investigate the association between SGLT2 inhibitors and eu-DKA in COVID-19 patients through meticulous case report analysis.Additionally,we endeavor to examine the outcomes and treatment approaches for COVID-19-infected diabetics receiving SGLT2 inhibitors,providing indispensable insights for healthcare professionals managing this specific patient population.AIM To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports.METHODS We conducted an exhaustive search across prominent electronic databases,including PubMed,SCOPUS,Web of Science,and Google Scholar.This search encompassed the period from December 2019 to May 2022,incorporating published studies and pre-prints.The search terms employed encompassed“SGLT2 inhibitors”,“euglycemic DKA”,“COVID-19”,and related variations.By incorporating these diverse sources,our objective was to ensure a thorough exploration of the existing literature on this subject,thereby augmenting the validity and robustness of our findings.RESULTS Our search yielded a total of seven case reports and one case series,collectively comprising a cohort of twelve patients.These reports detailed instances of eu-DKA in individuals with COVID-19.Crucially,all twelve patients were utilizing SGLT2 as their primary anti-diabetic medication.Upon admission,all oral medications were promptly discontinued,and the patients were initiated on intravenous insulin therapy to effectively manage the DKA.Encouragingly,eleven patients demonstrated a favorable outcome,while regrettably,one patient succumbed to the condition.Subsequently,SGLT2 were discontinued for all patients upon their discharge from the hospital.These findings provide valuable insights into the clinical management and outcomes of eu-DKA cases associated with COVID-19 and SGLT2,underscoring the critical importance of prompt intervention and vigilant medication adjustments.CONCLUSION Our study sheds light on the possibility of diabetic patients developing both drug-related and unrelated DKA,as well as encountering adverse outcomes in the context of COVID-19,despite maintaining satisfactory glycemic control.The relationship between glycemic control and clinical outcomes in COVID-19 remains ambiguous.Consequently,this systematic review proposes that COVID-19-infected diabetic patients using SGLT2 should contemplate alternative treatment protocols until their recovery from the disease.展开更多
文摘With notable Reno protective advantages beyond glycemic management,sodiumglucose cotransporter-2(SGLT2)inhibitors have become a mainstay treatment for type 2 diabetes mellitus and chronic kidney disease(CKD).Although SGLT2 inhibitors'involvement in the course of CKD has been well investigated,new research indicates that they may also have protective benefits in acute kidney injury(AKI),a condition for which there are few pharmacological treatments.The possible ways that SGLT2 inhibitors aid in AKI recovery are examined in this mini-review.These include mitochondrial protection,oxidative stress attenuation,anti-inflammatory effects,intraglomerular pressure decrease,and modulation of tubuloglomerular feedback.Although there is a lack of solid clinical trial data,preclinical models and observational studies suggest that SGLT2 inhibitors may lessen ischemia-reperfusion injury and contrast-induced nephropathy.This review addresses the possibility of incorporating SGLT2 inhibitors into AKI care regimens,critically evaluates the available data,and highlights important research gaps.Robust clinical trials are required to determine the safety,effectiveness,and ideal treatment window of SGLT2 inhibitors in this context,given the burden of AKI-related morbidity and mortality.
文摘AIM:To investigate the effects of dipeptidyl peptidase-4 inhibitors(DPP4i)and sodium-glucose cotransporter-2 inhibitors(SGLT2i)on diabetic macular edema(DME)and the need for intravitreal injections(IVT)in patients with type 2 diabetes.METHODS:Data were retrospectively collected from the medical records of patients with diabetic retinopathy(DR)taking either DPP4i or SGLT2i as secondary oral hypoglycemic agents in addition to metformin between January 2019 and July 2022.We compared the prevalence of DME and the need for IVT among patients treated with DPP4i or SGLT2i.Propensity score matching was performed using the following variables:age,duration of diabetes,blood glucose control(HbA1c)level,and severity of DR.RESULTS:A total of 268 patients with DR were included in this study.More DPP4i users needed IVT than SGLT2i users(35.3%vs 18.0%,P=0.011),while the prevalence of DME was not different.The use of SGLT2i was associated with a lower need for IVT than DPP4i[odds ratio(OR)0.404,95%confidence interval(CI)0.198-0.823],and similar trends were observed after propensity score matching(OR 0.419,95%CI 0.181-0.970).However,this tendency was not significant in multiple logistic regressions.For DME,the use of DPP4i was not a significant risk factor compared to SGLT2i.CONCLUSION:The use of SGLT2i may be associated with a lower need for IVT for overall DR complications,while other factors may contribute to this effect.The effect of SGLT2i on the prevention of DME is not evident.
基金Peking University First Hospital Institutional Review Board(No.2018104).
文摘BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose cotransporter-2 inhibitor(SGLT2i)and/or glucagon like peptide-1 receptor agonists(GLP-1RAs)for renal protection.The real-world efficacy of the two medications on the urinary albumin-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR)remains to be explored.AIM To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.METHODS A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months.Propensity score matching was performed,and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio.Blood glucose,body weight,UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.RESULTS A total of 139(2.54%)patients started GLP-1RA,and 387(7.06%)received SGLT2i.After 6 months,the variations in fasting blood glucose,prandial blood glucose,and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different.UACR showed a tendency toward a greater reduction compared with the control group,although this difference was not statistically significant(GLP-1RA vs control,-2.20 vs 30.16 mg/g,P=0.812;SGLT2i vs control,-20.61 vs 12.01 mg/g,P=0.327);eGFR alteration also showed no significant differences.Significant weight loss was observed in the GLP-1RA group compared with the control group(GLP-1RA vs control,-0.90 vs 0.27 kg,P<0.001),as well as in the SGLT2i group(SGLT2i vs control,-0.59 vs-0.03 kg,P=0.010).CONCLUSION Compared with patients who received other glucose-lowering drugs,patients receiving SGLT2i or GLP-1RAs presented significant weight loss,a decreasing trend in UACR and comparable glucose-lowering effects in realworld settings.
基金Supported by Science and Technology Department of Yunnan Province-Kunming Medical University,Kunming Medical Joint Special Project-Surface Project,No.202401AY070001-164Yunnan Provincial Clinical Research Center Cardiovascular Diseases-New Technology Research for Development Project for Diagnosis and Treatment Cardiovascular Diseases,No.202102AA310002the Key Technology Research and Device Development Project for Innovative Diagnosis and Treatment of Structural Heart Disease in the Southwest Plateau Region,No.202302AA310045.
文摘Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequently augmenting urinary glucose excretion and attenuating blood glucose levels.Extensive clinical investigations have demonstrated their profound cardiovascular efficacy.Parallel basic science research has elucidated the mechanistic pathways through which diverse SGLT-2 inhibitors beneficially modulate pulmonary vascular cells and arterial remodeling.Specifically,these inhibitors exhibit promising potential in enhancing pulmonary vascular endothelial cell function,suppressing pulmonary smooth muscle cell proliferation and migration,reversing pulmonary arterial remodeling,and maintaining hemodynamic equilibrium.This comprehensive review synthesizes current literature to delineate the mechanisms by which SGLT-2 inhibitors enhance pulmonary vascular cell function and reverse pulmonary remodeling,thereby offering novel therapeutic perspectives for pulmonary vascular diseases.
文摘BACKGROUND Sodium-glucose cotransporter-2 inhibitors(SGLT2i)are commonly prescribed to manage patients with diabetes mellitus.These agents may rarely lead to the development of euglycemic diabetic ketoacidosis(EDKA),which may complicate the disease course of these patients.AIM To analyze the demographic profile,predisposing factors,symptomology,clinical interventions and outcomes of patients presenting with EDKA secondary to SGLT2i use by reviewing the published case reports and series.METHODS We performed a systematic search of PubMed,Science Direct,Google Scholar and Reference Citation Analysis databases using the terms“canagliflozin”OR“empagliflozin”OR“dapagliflozin”OR“SGLT2 inhibitors”OR“Sodium-glucose cotransporter-2”AND“euglycemia”OR“euglycemic diabetic ketoacidosis”OR“metabolic acidosis”.The inclusion criteria were:(1)Case reports or case series with individual patient details;and(2)Reported EDKA secondary to SGLT2i.Furthermore,the data were filtered from the literature published in the English language and on adults(>18 years).We excluded:(1)Conference abstracts;and(2)Case reports or series which did not have individual biochemical data.All the case reports and case series were evaluated.The data extracted included patient demographics,clinical symptomatology,clinical interventions,intensive care unit course,need for organ support and outcomes.RESULTS Overall,108 case reports and 17 cases series with 169 unique patients that met all the inclusion criteria were included.The majority of patients were females(54.4%,n=92),and the commonly reported symptoms were gastrointestinal(nausea/vomiting 65.1%,abdominal pain 37.3%)and respiratory(breathlessness 30.8%).One hundred and forty-nine(88.2%)patients had underlying type II diabetes,and the most commonly involved SGLT-2 inhibitor reported was empagliflozin(46.8%).A triggering factor was reported in most patients(78.7%),the commonest being acute severe infection(37.9%),which included patients with sepsis,coronavirus disease 2019,other viral illnesses,and acute pancreatitis.61.5%were reported to require intensive unit care,but only a minority of patients required organ support in the form of invasive mechanical ventilation(13%),vasopressors(6.5%)or renal replacement therapy(5.9%).The overall mortality rate was only 2.4%.CONCLUSION Patients on SGLT2i may rarely develop EDKA,especially in the presence of certain predisposing factors,including severe acute infections and following major surgery.The signs and symptoms of EDKA may be similar to that of DKA but with normal blood sugar levels,which may make the diagnosis challenging.Outcomes of EDKA are good if recognized early and corrective actions are taken.Hence,physicians managing such patients must be aware of this potential complication and must educate their patients accordingly to ensure early diagnosis and management.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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
文摘Sodium-glucose cotransporter-2(SGLT2)inhibitors have emerged as a pivotal intervention in diabetes management,offering significant cardiovascular benefits.Empagliflozin,in particular,has demonstrated cardioprotective effects beyond its glucose-lowering action,reducing heart failure hospitalizations and improving cardiac function.Of note,the cardioprotective mechanisms appear to be independent of glucose lowering,possibly mediated through several mechanisms involving shifts in cardiac metabolism and anti-fibrotic,anti-inflammatory,and anti-oxidative pathways.This editorial summarizes the multifaceted cardiovascular advantages of SGLT2 inhibitors,highlighting the need for further research to elucidate their full therapeutic potential in cardiac care.
文摘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 3<sup>rd</sup> 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 21<sup>st</sup> June 2023. Subsequently, the panel reviewed and discussed the supporting rationale of the revised recommendations. This article presents these practical recommendations.
文摘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.
文摘Mitochondrial dysfunction is a key driver of cardiovascular disease(CVD)in metabolic syndrome and diabetes.This dysfunction promotes the production of reactive oxygen species(ROS),which cause oxidative stress and inflammation.Angiotensin II,the main mediator of the renin-angiotensin-aldosterone system,also contributes to CVD by promoting ROS production.Reduced activity of sirtuins(SIRTs),a family of proteins that regulate cellular metabolism,also worsens oxidative stress.Reduction of energy production by mitochondria is a common feature of all metabolic disorders.High SIRT levels and 5’adenosine monophosphate-activated protein kinase signaling stimulate hypoxia-inducible factor 1 beta,which promotes ketosis.Ketosis,in turn,increases autophagy and mitophagy,processes that clear cells of debris and protect against damage.Sodiumglucose cotransporter-2 inhibitors(SGLT2i),a class of drugs used to treat type 2 diabetes,have a beneficial effect on these mechanisms.Randomized clinical trials have shown that SGLT2i improves cardiac function and reduces the rate of cardiovascular and renal events.SGLT2i also increase mitochondrial efficiency,reduce oxidative stress and inflammation,and strengthen tissues.These findings suggest that SGLT2i hold great potential for the treatment of CVD.Furthermore,they are proposed as anti-aging drugs;however,rigorous research is needed to validate these preliminary findings.
文摘BACKGROUND Landmark trials have established the benefits of sodium-glucose cotransporter-2 inhibitors(SGLT2-Is)in cardiovascular disease including heart failure with reduced and preserved ejection fraction and renal diseases regardless of the presence of diabetes mellitus.However,studies evaluating the role of SGLT2-Is in metabolic syndrome(MetS)are limited.AIM This study primarily aimed to evaluate the impact of SGLT2-Is on the components of MetS.METHODS Two independent reviewers and an experienced librarian searched Medline,Scopus and the Cochrane central from inception to December 9,2021 to identify placebo controlled randomized controlled trials that evaluated the impact of SGLT2-Is on the components of MetS as an endpoint.Pre-and post-treatment data of each component were obtained.A meta-analysis was performed using the RevMan(version 5.3;Copenhagen:The Nordic Cochrane Center,The Cochrane Collaboration).RESULTS Treatment with SGLT2-Is resulted in a decrease in fasting plasma glucose(–18.07 mg/dL;95%CI:-25.32 to–10.82),systolic blood pressure(–1.37 mmHg;95%CI:-2.08 to–0.65),and waist circumference(–1.28 cm;95%CI:-1.39 to–1.18)compared to placebo.The impact on highdensity lipoprotein cholesterol was similar to placebo(0.01 mg/dL;95%CI:-0.05 to 0.07).CONCLUSION SGLT2-Is have a promising role in the management of MetS.
文摘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.
文摘BACKGROUND Diabetic ketoacidosis(DKA)manifests as hyperglycemia,metabolic acidosis,and ketosis.However,euglycemic DKA(eu-DKA)conceals severe DKA with glucose levels below 200 mg/dL.Sodium-glucose cotransporter-2(SGLT2)inhibitors can induce eu-DKA in diabetic patients.Notably,coronavirus disease 2019(COVID-19)-infected individuals with diabetes using SGLT2 inhibitors face an augmented risk of eu-DKA due to the direct toxic impact of the virus on pancreatic islets.This study aims to comprehensively investigate the association between SGLT2 inhibitors and eu-DKA in COVID-19 patients through meticulous case report analysis.Additionally,we endeavor to examine the outcomes and treatment approaches for COVID-19-infected diabetics receiving SGLT2 inhibitors,providing indispensable insights for healthcare professionals managing this specific patient population.AIM To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports.METHODS We conducted an exhaustive search across prominent electronic databases,including PubMed,SCOPUS,Web of Science,and Google Scholar.This search encompassed the period from December 2019 to May 2022,incorporating published studies and pre-prints.The search terms employed encompassed“SGLT2 inhibitors”,“euglycemic DKA”,“COVID-19”,and related variations.By incorporating these diverse sources,our objective was to ensure a thorough exploration of the existing literature on this subject,thereby augmenting the validity and robustness of our findings.RESULTS Our search yielded a total of seven case reports and one case series,collectively comprising a cohort of twelve patients.These reports detailed instances of eu-DKA in individuals with COVID-19.Crucially,all twelve patients were utilizing SGLT2 as their primary anti-diabetic medication.Upon admission,all oral medications were promptly discontinued,and the patients were initiated on intravenous insulin therapy to effectively manage the DKA.Encouragingly,eleven patients demonstrated a favorable outcome,while regrettably,one patient succumbed to the condition.Subsequently,SGLT2 were discontinued for all patients upon their discharge from the hospital.These findings provide valuable insights into the clinical management and outcomes of eu-DKA cases associated with COVID-19 and SGLT2,underscoring the critical importance of prompt intervention and vigilant medication adjustments.CONCLUSION Our study sheds light on the possibility of diabetic patients developing both drug-related and unrelated DKA,as well as encountering adverse outcomes in the context of COVID-19,despite maintaining satisfactory glycemic control.The relationship between glycemic control and clinical outcomes in COVID-19 remains ambiguous.Consequently,this systematic review proposes that COVID-19-infected diabetic patients using SGLT2 should contemplate alternative treatment protocols until their recovery from the disease.
