Receiving Sodium-glucose Cotransporter 2 Inhibitors Research Articles

Ketonuria as an Indicator of Improvement of Renal Function in Patients with Type 2 Diabetes Receiving SGLT2 Inhibitor Treatment.

We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, -0.02 mL/min/1.73 m2 [95% confidence interval (CI), -3.87 to 3.83 mL/min/1.73 m2] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m2 [95% CI, 3.16 to 10.46 mL/min/1.73 m2]; P<0.001). Improvement in estimated glomerular filtration rate at 6 months was associated with female sex and lower baseline body weight, blood pressure, and triglyceride levels in patients with ketonuria. In conclusion, the presence of ketonuria was associated with the renoprotective effect of SGLT2 inhibitors, and female sex and the absence of metabolic syndrome components may serve as additional indicators of these medications' substantial renoprotective effects in individuals with ketonuria.

The Effectiveness of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors on Cardiovascular Outcomes and All-Cause Mortality in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to investigate the impact of early sodium-glucose cotransporter-2 (SGLT2) initiation on long-term cardiovascular outcomes and all-cause mortality among patients with acute coronary syndrome (ACS).For this study, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline. Two researchers independently performed a comprehensive literature search on PubMed, Embase, and the Cochrane Library, spanning from the inception of each database to February 24, 2023, without language limitations. The outcomes examined in this meta-analysis comprised major adverse cardiovascular events (MACE) (as defined by individual studies), all-cause mortality, cardiovascular mortality, stroke (ischemic and hemorrhagic), recurrent ACS, and hospitalization due to heart failure (HF). A total of nine studies were included in this meta-analysis.The pooled analysis of nine studies revealed a significant reduction in the risk of MACE, all-cause mortality, cardiovascular mortality, and cardiovascular-related hospitalizations among patients receiving SGLT2 inhibitors (SGLT2i) compared to those in the control group. Additionally, there was a trend towarda lower risk of recurrent ACS in the SGLT2i group, although this difference did not reach statistical significance. The findings of this study suggest a promising therapeutic effect of SGLT2 inhibitors in this population. Further research, particularly focusing on myocardial infarction (MI) patients, is warranted to validate these results and potentially revolutionize ACS management.

Evaluation of the Lifetime Benefits of Metformin and SGLT2 Inhibitors in Type 2 Diabetes Mellitus Patients with Cardiovascular Disease: A Systematic Review and Two-Stage Meta-Analysis.

Metformin and sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardiovascular benefits but their comparative effects on mortality in type 2 diabetes mellitus (T2DM) patients with cardiovascular disease (CVD) are unknown. Hence, we evaluated and compared lifetime benefits arising from metformin or SGLT2 inhibitors in T2DM patients with CVD. Studies published in the PubMed, EMBASE and CENTRAL databases before 28 October 2023 were retrieved. Treatment effects of metformin against US FDA-approved SGLT2 inhibitors in T2DM patients with CVD were evaluated and lifetime gains in event-free survival were estimated from our primary endpoints of all-cause and cardiovascular mortality. Risk ratios were derived to assess their impact on secondary outcomes such as major adverse cardiovascular events and hospitalizations for heart failure. Overall, 14 studies were included. Five studies published Kaplan-Meier curves for the primary outcome of all-cause mortality. Individual participant data were reconstructed from these Kaplan-Meier curves, from which we conducted our two-stage meta-analysis. Participants receiving metformin and SGLT2 inhibitors experienced a reduction in the risk for all-cause mortality as compared with those not taking metformin and placebo. However, participants receiving SGLT2 inhibitors had a higher all-cause mortality (hazard ratio 1.308, 95% confidence interval 1.103-1.550) versus metformin. Treatment with metformin was estimated to offer an additional 23.26months of survival free from all-cause mortality versus 23.04months with SGLT2 inhibitors. In patients with T2DM and CVD, metformin and SGLT2 inhibitors were associated with substantially lower all-cause mortality rates and slightly longer life expectancies than in patients without. Metformin presented an advantage over SGLT2 inhibitors in reducing all-cause mortality.

Prolonged Diabetic Ketoacidosis Associated With Sodium–Glucose Cotransporter-2 Inhibitors: A Review of Postmarketing Cases

ObjectiveTo describe reported cases of prolonged or relapsed ketoacidosis (KA) in adults with type 2 diabetes receiving treatment with sodium–glucose cotransporter-2 (SGLT2) inhibitors. MethodsWe performed a search of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and medical literature, to identify our case series and to characterize cases of prolonged KA, relapsed KA, or persistent ketonemia, persistent ketonuria and/or persistent glucosuria in adults receiving SGLT2 inhibitors. ResultsThe FDA identified 29 unique cases of prolonged or relapsed KA, as well as related terms persistent ketonemia, persistent ketonuria, and persistent glucosuria, in patients receiving SGLT2 inhibitors through July 26, 2022. The patients ranged in age from 26 to 85 years. Treatment duration of KA ranged from 3 to 20 days. There were 7 cases of relapsed KA when insulin was reduced or transitioned to subcutaneous route. Arterial pH value was 7.0 or below in 4 patients, and the median pH was 7.1. Associated factors for prolonged or relapsed KA included surgery, decreased caloric intake, and ketogenic/carbohydrate restricted diet. A total of 62% of the patients were taking 3 or more glycemic control medications including the SGLT2 inhibitor. All patients with sufficient follow-up information recovered. ConclusionAlthough KA is a well-known risk associated with SGLT2 inhibitors, this case series demonstrated the potential for prolonged or recurrent KA events with serious outcomes. These cases informed updates to FDA's prescribing information to inform prescribers of this risk.

Use of SGLT2 Inhibitors vs GLP-1 RAs and Anemia in Patients With Diabetes and CKD

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with lower anemia risk, based on findings from post hoc analyses of the CREDENCE and DAPA-CKD trials; however, the effectiveness of SGLT2 inhibitors in a more generalizable type 2 diabetes (T2D) and chronic kidney disease (CKD) population, with active comparisons pertinent to current practice, is unknown. To evaluate and compare anemia incidence between SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among patients with T2D and CKD stages 1 to 3. This retrospective cohort study used target trial emulation of an expanded CREDENCE and DAPA-CKD study framework. The study was conducted among adults with T2D and CKD initiating SGLT2 inhibitors or GLP-1 RAs between January 1, 2016, and December 31, 2021, with follow-up until December 31, 2022. The study was conducted at the Chang Gung Medical Foundation, the largest multi-institutional hospital system in Taiwan. Initiation of SGLT2 inhibitors or GLP-1 RAs. The primary outcome was a composite of anemia outcomes, including anemia event occurrence (hemoglobin level <12-13 g/dL or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes) or anemia treatment initiation. Changes in hematological parameters, including hemoglobin level, hematocrit level, and red blood cell count, were evaluated during the follow-up period for as long as 3 years. The cohort included a total of 13 799 patients with T2D and CKD, initiating SGLT2 inhibitors (12 331 patients; mean [SD] age, 62.4 [12.3] years; 7548 [61.2%] male) or GLP-1 RAs (1468 patients; mean [SD] age, 61.5 [13.3] years; 900 [61.3%] male). After the median follow-up period of 2.5 years, patients receiving SGLT2 inhibitors had lower incidence of composite anemia outcomes (hazard ratio [HR], 0.81; 95% CI, 0.73-0.90) compared with those receiving GLP-1 RAs. SGLT2 inhibitors were associated with a lower incidence of anemia events (HR, 0.79; 95% CI, 0.71-0.87) but not with a lower rate of anemia treatment initiation (HR, 0.99; 95% CI, 0.83-1.19). Changes in hematological parameters for SGLT2 inhibitors and GLP-1 RAs throughout the 3-year follow-up period supported the primary analyses. In this multi-institutional cohort study with target trial emulation, SGLT2 inhibitors were associated with a decreased risk of composite anemia outcomes, especially anemia event occurrences. SGLT2 inhibitors may be considered as an adjunct therapy to reduce anemia incidence in patients with T2D and CKD.

Effects of newer-generation anti-diabetics on diabetic retinopathy: a critical review.

Diabetic retinopathy (DR) is the leading etiology of blindness in the working population of the USA. Its long-term management relies on effective glycemic control. Seven anti-diabetic classes have been introduced for patients with type 2 diabetes (T2D) in the past two decades, with different glucose-lowering and cardiovascular benefits. Yet, their effects specifically on DR have not been studied in detail. A systematic review of the literature was conducted to investigate this topic, focusing on the available clinical data for T2D. Published studies were evaluated based on their level of statistical evidence, as long as they incorporated at least one endpoint or adverse event pertaining to retinal health. Fifty nine articles met our inclusion criteria and were grouped per anti-diabetic class as follows: alpha-glucosidase inhibitors (1), peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists (8), amylin analogs (1), glucagon-like peptide-1 (GLP-1) receptor agonists (28), dipeptidyl peptidase 4 (DPP-4) inhibitors (9), and sodium glucose co-transporter-2 (SGLT-2) inhibitors (9), plus one retrospective study and two meta-analyses evaluating more than one of the aforementioned anti-diabetic categories. We also reviewed publicly-announced results of trials for the recently-introduced class of twincretins. The available data indicates that most drugs in the newer anti-diabetic classes are neutral to DR progression; however, there are subclasses differences in specific drugs and T2D populations. In particular, there is evidence suggesting there may be worse diabetic macular edema with PPAR-gamma agonists, potential slight DR worsening with semaglutide (GLP-1 receptor agonist), and potential slight increase in the incidence of retinal vein occlusion in elderly and patients with advanced kidney disease receiving SGLT-2 inhibitors. All these warrant further investigation. Longer follow-up and systematic assessment of at least one DR-related endpoint are highly recommended for all future trials in the T2D field, to ultimately address this topic.

Sodium-glucose cotransporter-2 inhibitor-associated euglycemic diabetic ketoacidosis in COVID-19-infected patients: A systematic review of case reports.

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. To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports. 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. 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. 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.

Utilization Rates of SGLT2 Inhibitors Among Patients With Type 2 Diabetes, Heart Failure, and Atherosclerotic Cardiovascular Disease: Insights From the Department of Veterans Affairs

BackgroundMultiple clinical trials have demonstrated significant cardiovascular benefit with use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2DM) and heart failure (HF) irrespective of ejection fraction. There are limited data evaluating real-world prescription and practice patterns of SGLT2 inhibitors. ObjectivesThe authors sought to assess utilization rates and facility-level variation in the use among patients with established atherosclerotic cardiovascular disease (ASCVD), HF, and T2DM using data from the nationwide Veterans Affairs health care system. MethodsThe authors included patients with established ASCVD, HF, and T2DM seen by a primary care provider between January 1, 2020, and December 31, 2020. They assessed the use of SGLT2 inhibitors and the facility-level variation in their use. Facility-level variation was computed using median rate ratios, a measure of likelihood that 2 random facilities differ in use of SGLT2 inhibitors. ResultsAmong 105,799 patients with ASCVD, HF, and T2DM across 130 Veterans Affairs facilities, 14.6% received SGLT2 inhibitors. Patients receiving SGLT2 inhibitors were younger men with higher hemoglobin A1c and estimated glomerular filtration rate and were more likely to have HF with reduced ejection fraction and ischemic heart disease. There was significant facility-level variation of SGLT2 inhibitor use, with an adjusted median rate ratio of 1.55 (95% CI: 1.46-1.64), indicating a 55% residual difference in SGLT2 inhibitor use among similar patients with ASCVD, HF, and T2DM receiving care at 2 random facilities. ConclusionsUtilization rates of SGLT2 inhibitors are low in patients with ASCVD, HF, and T2DM, with high residual facility-level variation. These findings suggest opportunities to optimize SGLT2 inhibitor use to prevent future adverse cardiovascular events.

Use of Sodium-Glucose Cotransporter-2 Inhibitor for Diabetes Management in Patients Following Kidney Transplantation.

Objective: To evaluate data sources pertaining to the safety and efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitor use for diabetes management in patients following kidney transplantation. Data Sources: A literature search was conducted through PubMed (1966-January 2023), EMBASE (1973-January 2023), and clinicaltrials.gov databases using the search terms kidney transplantation, diabetes mellitus, and SGLT2 inhibitor or empagliflozin, dapagliflozin, and canagliflozin. Study Selection and Data Extraction: Studies evaluating human kidney transplant recipients (KTR) receiving SGLT2 inhibitors treatment and published in the English language were included. Eight case series or retrospective analyses, 4 prospective observational studies, and 1 randomized controlled trial were identified. Data Synthesis: Available literature provides evidence that the addition of SGLT2 inhibitors may provide modest benefits on glycemic control, body weight, and serum uric acid levels in certain KTR. Various studies and case reports found that incidence of urinary tract infections was low, but still present. Overall, there are limited data on mortality and graft survival; however, one study reported a benefit of SGLT2 inhibitor use in KTR relative to these outcomes. Conclusions: The current literature evaluated demonstrates that there may be benefit to the addition of SGLT2 inhibitors for diabetes management in select KTR. However, the limited evidence within a large diverse population and extended duration of treatment makes it difficult to definitively identify the true efficacy and safety of SGLT2 inhibitor use in this population.

58. Blood Pressure Reduction Effect of Dapagliflozin in Patients with Type 2 Diabetes Mellitus: a Systematic Review

Hypertension is a common comorbidity in patients with Type 2 Diabetes Mellitus (T2DM). One of the new anti-diabetic classes is Sodium-Glucose Cotransporter-2 (SGLT2) inhibitor which is still widely tested in clinical trials for indications beyond T2DM. However, the effect on blood pressure in T2DM patients receiving SGLT2 inhibitors is still not well known. This study wants to find out the effect of Dapagliflozin on blood pressure in patients with T2DM. This study was conducted on 1–7 January 2023. Two independent researchers systematically extracted data from several databases, such as PubMed Central (PMC), Science Direct, and PUBMED by using MeSH terminology of keywords SGLT2 inhibitor and blood pressure. The extracted studies were then analyzed and selected according to our inclusion criteria such as studies in the last 5 years, T2DM patients receiving dapagliflozin, cohort studies, and case-control studies. We excluded systematic reviews, meta-analyses, case series, case reports, studies on pregnant women, children, and animals. Research quality was assessed using Newcastle-Ottawa (NOS). From 4 cohort studies (1664 subjects from various countries), all of them showed dapagliflozin administration resulted in reduction of systolic blood pressure. In some studies, the blood pressure-lowering effect of dapagliflozin administration was greater when combined with other classes of anti-diabetic drugs like Glucagon-Like Peptide-1 (GLP1) agonist; All studies have proven good quality based on NOS. In conclusion, dapagliflozin had a blood pressure-lowering effect in T2DM patients. However, further study is needed to confirm these findings.

Patients with diabetes with and without sodium-glucose cotransporter-2 inhibitors use with incident cancer risk

PurposeThe study compared the incidence of cancer between patients with diabetes with and without sodium-glucose cotransporter-2 (SGLT2) inhibitors use. MethodsThis study identified a non-SGLT2 inhibitor cohort of 325,989 patients and a SGLT2 inhibitor cohort of 325,990 patients. The primary interest of this study was the occurrence of cancer. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models. ResultsPatients receiving SGLT2 inhibitors (adjusted HR = 0.79, 95 % CI = 0.76–0.83) had a significantly lower risk of developing cancer than patients without receiving SGLT2 inhibitors. ConclusionThe results demonstrated that patients with diabetes receiving SGLT2 inhibitors had a significantly lower risk of cancer.

Dosing of iron supplementation for iron-deficient patients with heart failure: should we prefer more intensive or less intensive repletion targets?

Dosing of iron supplementation for iron-deficient patients with heart failure: should we prefer more intensive or less intensive repletion targets?

Efficacy and Safety of Sodium Glucose Cotransporter-2 (SGLT2) Inhibitors in Patients With Diabetes and Chronic Kidney Disease (CKD): A Meta-analysis of Randomized Control Trials.

The current meta-analysis aims to assess the efficacy and safety of sodium glucose cotransporter 2 (SGLT2) inhibitors in individuals with diabetes and chronic kidney disease (CKD). The current meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was conducted to identify all relevant studies related to the efficacy and safety of SGLT2 inhibitors in individuals with diabetes and CKD. The search was undertaken in PubMed, EMBASE, and Cochrane Library from January 2000 to September 2022. The primary efficacy outcome assessed in the current meta-analysis included major adverse cardiovascular events (MACE). Other efficacy outcomes included all-cause mortality and change in hemoglobin A1c (HbA1c) (%). Safety outcomes included serious adverse events, acute kidney injury, hypoglycemia, and hyperkalemia. In total 11 articles met the inclusion criteria and were included in the final analysis enrolling 27520 patients (14491 in the SGLT2 inhibitors and 13029 in the placebo group). The findings of this meta-analysis have shown that the risk of MACE and all-cause mortality was significantly lower in patients receiving SGLT2 inhibitors. Additionally, Hb1AC change was also significantly greater in SGLT2 inhibitors group. In relation to safety outcomes, serious adverse events, risk of acute kidney injury, and hyperkalemia were significantly lower in the SGLT2 inhibitors group. The SGLT2 inhibitors significantly decreased the risk of major cardiovascular events and all-cause mortality in patients with CKD and diabetes. Furthermore, SGLT2 inhibitor is also effective in reducing Hb1Ac levels in patients.

SGLT2 Inhibitors in Acute Heart Failure: A Meta-Analysis of Randomized Controlled Trials.

Acute heart failure (AHF) is a major public health concern, affecting 26 million worldwide. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering drugs, comprising canagliflozin, dapagliflozin, and empagliflozin that are being explored for AHF. We aim to meta-analyze the effectiveness of SGLT2 inhibitors compared to placebo for primary outcomes including all-cause and cardiovascular mortality, heart failure events, symptomatic improvement, and readmissions. Our secondary outcome is the risk of serious adverse events. This meta-analysis has been designed in accordance with the PRISMA Statement 2020. A systematic search across PubMed, Scopus, and Cochrane Library was conducted through August 13, 2022. The following keywords were utilized: sglt2, sodium-glucose transporter 2 inhibitors, sglt2 inhibitors, decompensated heart failure, de-novo heart failure, and/or acute heart failure. Only randomized controlled trials (RCTs) with adult patients (&gt;18 years), hospitalized with de-novo AHF, acutely decompensated chronic heart failure with reduced, borderline, or preserved ejection, and receiving SGLT2 inhibitors were included. A quantitative analytical methodology was applied where the standardized mean difference (SMD) applying 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) with 95% CI was yielded. All tests were carried out on Review Manager 5.4 (Cochrane). In total, three RCTs were included pooling in a total of 1831 patients where 49.9% received SGLT2 inhibitors. The mean age was 72.9 years in the interventional group compared to 70.6 years in the placebo. Only 33.7% of the sample was female. The follow-up spanned 2-9 months. Heart failure events were reduced by 62% in the interventional group (RR = 0.66, p &lt; 0.0001). readmissions had a reduced risk of 24% with SGLT2 inhibitors (RR = 0.76, p = 0.03). We assessed the efficacy and safety of SGLT2 inhibitors in preventing complications post-AHF. The odds of all-cause mortality, cardiovascular mortality, heart failure events, and re-admissions rates were substantially reduced within the first 1-9 months of hospitalization.

Clinical Prognosis in Patients with Heart Failure and Reduced Left Ventricular Ejection Fraction after Myocardial Revascularization on the Background of Taking SGLT2 Inhibitors

The aim. To evaluate clinical and prognostic effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on primary (progression of heart failure, rehospitalization) and secondary endpoints (death from cardiovascular disease and from all causes) in patients with heart failure with reduced ejection fraction (HFrEF) within 8 months after percutaneous coronary intervention (PCI).&#x0D; Materials and methods. In a one-center study on the basis of the Ukrainian Children’s Cardiac Center, Clinic for Adults we analyzed the data for drug and interventional treatment of 166 patients with coronary artery disease and reduced left ventricular ejection fraction (LVEF) (&lt;40%), who underwent PCI in the last 8 months. Among the 166 patients studied, 86 (51.8%) patients received SGLT2 inhibitors as an adjunct to the standard baseline therapy, and 80 (48.2%) patients did not receive SGLT2 inhibitors after PCI.&#x0D; Results and discussion. The primary combined outcome was observed in 10 patients (6.02%) in the group of patients taking SGLT2 inhibitors and 35 patients (21.08%) without addition of SGLT2 inhibitors (hazard ratio 0.72; 95% CI, 0.65-0.85; p &lt;0.001). The incidence of the secondary combined result was lower in the group receiving SGLT2 inhibitors than in the comparison group (risk ratio, 0.85; 95% CI, 0.75-0.95; p &lt;0.001).&#x0D; Conclusions. The use of SGLT2 inhibitors in addition to the standard therapу provided a 72% reduction in the relative risk, estimated by the incidence of primary combined endpoint in particular, hospitalization due to the heart failure decompensation by 34% in the same group, and the secondary endpoint by 50%. The advantage of SGLT2 inhibitors over the standard therapy in the effect on the primary endpoint did not depend on the complete or incomplete myocardial revascularization by PCI in patients over an 8-month follow-up period. SGLT2 inhibitors use in patients after PCI with reduced left ventricular systolic function over the 8-month follow-up period led to regression of angina according to the KCCQ-TSS questionnaire, decreased functional class according to the New York classification, and increased LVEF.

Discordance in the reduction rate between glycated albumin and glycated hemoglobin levels in type 2 diabetes patients receiving SGLT2 inhibitors

AimsAlthough the difference in HbA1c reduction between sodium-glucose cotransporter 2 (SGLT2) inhibitors and other oral glucose-lowering agents is relatively small, SGLT2 inhibitors exhibit beneficial cardiorenal protection. This study was based on the hypothesis that changes of HbA1c in patients treated with SGLT2 inhibitors may not accurately reflect an improved glycemic profile. MethodsTwo studies were conducted: 1) a retrospective cohort study of 3039 patients administered with either an SGLT2 or a dipeptidyl peptidase-4 (DPP4) inhibitor for 12 months comparing the changes in glycated albumin (GA) and HbA1c levels and 2) a pilot study of 10 patients whose glycemic dynamics were evaluated using flash glucose monitoring at baseline and 2 months after treatment with an SGLT2 inhibitor. ResultsSGLT2 inhibitors reduced GA more markedly than HbA1c in both studies. DPP4 inhibitors decreased both GA and HbA1c to a comparable degree. The mean glucose levels and glycemic standard deviation were significantly reduced after treatment with an SGLT2 inhibitor, in concordance with GA decline, although the lowering of HbA1c was marginal. ConclusionsChanges in HbA1c levels underestimated the glucose-lowering effect and the diminished glycemic fluctuation induced by SGLT2 inhibitors. Thus, the distinct biomarker roles of GA and HbA1c should be reevaluated.

Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Heart Failure : A Systematic Review and Meta-analysis.

Randomized controlled trials established the cardiac protection of sodium-glucose cotransporter-2 (SGLT2) inhibitors among adults with type 2 diabetes. New evidence suggests that these results could extend to people without diabetes. To evaluate the effect of SGLT2 inhibitors in patients with heart failure, regardless of the presence of type 2 diabetes. PubMed, Web of Science, Cochrane Library, and Embase (OVID interface). Eligible trials randomly assigned adults with heart failure to SGLT2 inhibitors or control. Time-to-event individual patient data were reconstructed from published Kaplan-Meier plots; time-varying risk ratios (RRs) were calculated in half-, 1-, and 2-year time frames; and anticipated absolute benefits were calculated using simple models applying relative effects to baseline risks. Sodium-glucose cotransporter-2 inhibitors reduce hospitalization for heart failure by 37% (95% CI, 25% to 47%) at 6 months, 32% (CI, 20% to 42%) at 1 year, and 26% (CI, 10% to 40%) at 2 years (all high certainty) and reduce cardiovascular death by 14% (CI, 1% to 25%) at 1 year (high certainty). Nevertheless, low-certainty evidence did not indicate protection against all-cause death, kidney disease progression, or kidney failure. Anticipated absolute benefits are greater for patients treated in the first year and for those with poorer prognoses, such as those newly diagnosed with heart failure in the hospital. In addition, SGLT2 inhibitors doubled the risk for genital infections (RR, 2.69 [CI, 1.61 to 4.52]; high certainty). Covariates were unavailable in meta-analyses with reconstructed individual patient data. Among people with heart failure, SGLT2 inhibitors reduce hospitalizations for heart failure regardless of the presence of diabetes; absolute benefits are most pronounced in first-year treatment and vary with prognostic factors. Clinicians should note the increased risk for genital infection in patients receiving SGLT2 inhibitors. 1.3.5 Project for Disciplines of Excellence, West China Hospital of Sichuan University. (PROSPERO: CRD42021255544).

A Scoping Review Evaluating the Effect of SGLT-2 Inhibitors on Insulin Dose Requirements in Insulin-Dependent Patients With Type 2 Diabetes.

Assess evidence describing the effect of Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors on total daily insulin (TDI) requirements in insulin-dependent patients with type 2 diabetes. A scoping review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Protocols and Scoping Reviews (PRISMA-ScR) guidelines. The search was conducted in PubMed; citation mapping was completed in Web of Science. Filters for human studies, English language, and a publication date, from January 1, 2005 to April 12, 2021, were applied. Studies assessing insulin dose requirements with concurrent use of an SGLT2 inhibitor for patients with type 2 diabetes were included. Sixteen studies were included and demonstrated that addition of an SGLT2 inhibitor typically reduced TDI requirements. Insulin reductions were often statistically significant, occurring in studies evaluating (1) within subjects who received SGLT2 inhibitors, and (2) between subjects receiving SGLT2 inhibitors versus placebo. Compared with placebo, insulin dose reduction ranged from -0.72 to -19.2 units. However, studies were relatively small, not designed to assess TDI change, and some utilized fixed dose insulin protocols or empiric insulin dose reductions. Lowering insulin requirements may have benefits, such as decreased hypoglycemia risk, insulin resistance, and cost. Addition of an SGLT2 inhibitor may modestly reduce TDI requirements for patients with type 2 diabetes. Evidence indicating SGLT2 inhibitor use reduces TDI may lead to additional implementation in practice and inform future research. Further research is needed to clarify insulin type (i.e., basal or prandial) and degree of TDI reduction expected with addition of an SGLT2 inhibitor.

Association between sodium glucose co-transporter 2 inhibitors and incident glaucoma in patients with type 2 diabetes: A multi-institutional cohort study in Taiwan

PurposeType 2 diabetes (T2D) is an important risk factor for glaucoma, and sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to protect the optic nerves. We therefore aimed to evaluate the association between SGLT2 inhibitors and incident glaucoma. MethodsThis retrospective cohort study analyzed the largest multi-institutional electronic medical records database in Taiwan, containing data of over a million individuals. We included T2D patients newly prescribed SGLT2 inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) from 2016 to 2018. Our primary outcome was incident glaucoma diagnosis between initiation of SGLT2 inhibitors or GLP-1 RAs, and 31st March 2021. After applying inverse probability of treatment weighting (IPTW) to increase homogeneity between the two treatment groups, we estimated hazard ratios (HR) with 95% confidence intervals (CI) for the risk of glaucoma, based on Cox proportional hazards regression models. ResultsWe included 9,927 and 1,065 T2D patients who had been newly prescribed SGLT2 inhibitors or GLP-1 RAs, respectively. Lower risk of incident glaucoma was observed in patients receiving SGLT2 inhibitors (7.9 events per 1,000 person-years), compared to those receiving GLP-1 RAs (10.0 events per 1,000 person-years), with an HR of 0.81 (95% CI: 0.69–0.95). Multiple sensitivity analyses and a negative control outcome analysis confirmed the robustness of our main findings. ConclusionThis study suggests that T2D patients newly prescribed SGLT2 inhibitors have a reduced risk of incident glaucoma, compared to those prescribed GLP-1 RAs, in clinical practice. Future prospective studies are suggested to confirm this association.

Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors on Cardiac Imaging Parameters: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Recent studies have shown that sodium/glucose cotransporter 2 (SGLT2) inhibitors might exert favourable changes on cardiac parameters as observed on cardiovascular imaging. We conducted a systematic review and meta-analysis to determine the effects of SGLT2 inhibitors on cardiac imaging parameters. Four electronic databases (PubMed, Embase, Cochrane, Scopus) were searched for studies in which the effects of SGLT2 inhibitors on cardiac imaging parameters were examined. Studies in which a population was administered SGLT2 inhibitors and analysed by echocardiography and/or cardiac magnetic resonance (CMR) imaging were included. Random-effects pair-wise meta-analysis models were utilized to summarize the studies. A total of 11 randomized controlled trials was included with a combined cohort of 910 patients. Comparing patients receiving SGLT2 inhibitors with subjects receiving placebo, the mean change in CMR-measured left ventricular mass (LVM) was −3.87 g (95% confidence interval [CI], −7.77 to 0.04), that in left ventricular end-systolic volume (LVESV) was −5.96 mL (95% CI, −10.52 to −1.41) for combined LVESV outcomes, that in left atrial volume index (LAVi) was −1.78 mL/m2 (95% CI, −3.01 to −0.55) for combined LAVi outcomes, and that in echocardiography-measured E/e′ was −0.73 (95% CI, −1.43 to −0.03). Between-group differences were not observed in LVM and LVESV after indexation. The only between-group difference that persisted was for LAVi. Treatment with SGLT2 inhibitors resulted in reduction in LAVi and E/e′ on imaging, indicating they might have an effect on outcomes associated with LV diastolic function.