Prescribed Sodium-glucose Cotransporter 2 Inhibitors Research Articles

Body weight change associated kidney outcomes of sodium-glucose cotransporter new users.

To investigate the clinical significance of body weight changes on kidney outcomes among individuals with diabetes using sodium-glucose cotransporter-2 (SGLT2) inhibitors. This is a retrospective cohort study using a nationwide epidemiological database, and we conducted an analysis involving 11 569 individuals with diabetes who were newly prescribed SGLT2 inhibitors. The main outcome was the rate of decline in estimated glomerular filtration rate (eGFR), determined through a linear mixed-effects model with an unstructured covariance structure. The median age of the patients was 52 (Q1-Q3: 47-58) years, and the median fasting plasma glucose and glycated haemoglobin (HbA1c) levels were 144 (Q1-Q3: 124-175) mg/dL and 7.4 (Q1-Q3: 6.8-8.3)%, respectively. The median estimated eGFR was 77.7 (Q1-Q3: 67.2-89.1) mL/min/1.73 m2. The median follow-up period was 1.7 (Q1-Q3: 1.0-2.6) years. Participants were stratified into three groups based on the body mass index change rate tertiles between baseline and 1 year after (tertile 1: <-4.55%, tertile 2: -4.55% to -1.43%, tertile 3: >-1.43%). The annual change in eGFR was -0.78 (-0.94 to -0.63) mL/min/1.73 m2 in tertile 1, -0.95 (-1.09 to -0.81) mL/min/1.73 m2 in tertile 2, and -1.65 mL/min/1.73 m2 (-1.84 to -1.47) in tertile 3 (pinteraction < 0.001). A variety of sensitivity analyses confirmed the relationship between the 1-year body mass index decrease and favourable kidney outcomes after SGLT2 inhibitor administration. Our analysis of a nationwide epidemiological cohort revealed that kidney outcomes following the initiation of SGLT2 inhibitors would be more favourable, with greater body weight loss observed after the initiation of SGLT2 inhibitors.

Comparison over Time of Adverse Drug Reactions in Diabetes Patients Treated with Sodium-Glucose Cotransporter 2 Inhibitors.

The prescription of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been increasing due to their additional benefits, including weight loss, cardioprotection and renoprotection. Accordingly, there are concerns about the potential rise in severe adverse drug reactions (ADRs), such as urinary tract infections, diabetic ketoacidosis, volume depletion, and hypoglycemia. The Society has announced recommendations on the proper use of SGLT2 inhibitors. We aimed to elucidate the recent occurrence of severe ADRs which need discontinuation of SGLT2 inhibitors or hospitalization. In this retrospective cohort study, we identified 391 diabetic patients who were prescribed SGLT2 inhibitors upon admission to our hospital between April 2017 and March 2023. Of these, 68 patients who discontinued SGLT2 inhibitors for reasons other than ADRs were excluded. Patients were classified into the 2017 group and the 2020 group based on the treatment period of SGLT2 inhibitors, and the occurrence of ADRs and patient backgrounds were compared between the two groups. A total of 323 eligible patients were identified. Discontinuations of SGLT2 inhibitors decreased in the 2020 group (p < 0.05). However, discontinuations due to frailty increased (p < 0.05). Hospitalization due to ADRs, specifically those due to urinary tract infections, diabetic ketoacidosis, or volume depletion, did not specifically decrease (p = 0.273). This study indicated that there has been some improvement in the awareness of the proper use of SGLT2 inhibitors and there is still a need to continue enlightenment activities.

Kidney outcomes with SGLT2 inhibitor vs. DPP4 inhibitor use in older adults with diabetes.

While the kidney protective effects of sodium glucose co-transporter-2 (SGLT2) inhibitors have attracted much attention, there are limited real-world clinical data examining the effects of SGLT2 inhibitors on kidney function in older individuals. We aimed to compare the kidney outcomes between SGLT2 inhibitor and dipeptidyl peptidase 4 (DPP4) inhibitor use in older adults with diabetes. Using a nationwide claims database, we studied 6354 older adults (≥ 60 years of age) who had diabetes and newly initiated on SGLT2 inhibitors or DPP4 inhibitors. A 1:4 propensity score matching algorithm was used to compare changes in eGFR between SGLT2 inhibitor and DPP4 inhibitor users. The primary outcome was a decline in the rate of estimated glomerular filtration rate (eGFR), which was obtained using a linear mixed-effects model with an unstructured covariance. Following propensity score matching, 6354 individuals including 1271 SGLT2 inhibitor users and 5083 DPP4 inhibitor users (median age: 68 [65-70] years); men, 60.4%; median eGFR:69.0 [59.1-79.0] ml/min/1.73 m2, median hemoglobin A1c [HbA1c]:6.9 [6.5-7.4]%) were analyzed. SGLT2 inhibitor users had a slower eGFR decline than did DPP4 inhibitor users (-0.97 [95% CI, -1.24 to -0.70] ml/min/1.73m2 vs. -1.83 [95% CI, -1.97 to -1.69] ml/min/1.73m2 per year; p for interaction<0.001). This finding remained consistent across subgroups based on age, sex, body mass index, HbA1c level, renin-angiotensin system inhibitor use, and baseline eGFR. Additionally, the risk of a≥20%, ≥ 30%, and≥40% decrease in eGFR from baseline was significantly lower in SGLT2 inhibitor users than that in DPP4 inhibitor users. Our analysis, utilizing a nationwide epidemiological dataset, demonstrated that the decline in eGFR was slower in individuals aged≥60 years with diabetes who were prescribed SGLT2 inhibitors compared to those prescribed DPP4 inhibitors, suggesting a potential advantage of SGLT2 inhibitors for kidney outcomes even in older individuals with diabetes.

Cardiovascular outcomes between dapagliflozin versus empagliflozin in patients with diabetes mellitus.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been demonstrated to decrease cardiovascular adverse events. However, there is little real-world clinical evidence regarding a direct comparison between dapagliflozin and empagliflozin in patients with diabetes mellitus (DM). A difference in the cardiovascular efficancy of dapagliflozin versus empagliflozin in DM patients was anticipated, aiming to guide the optimal choice of SGLT2 inhibitors based on cardiovascular outcomes. From 2014 to 2020, a total of 1549 patients with DM who were prescribed SGLT2 inhibitors such as dapagliflozin or empagliflozin were retrospectively enrolled. We categorized the study population into two groups: dapagliflozin (n = 981) and empagliflozin group (n = 568). The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HF) over a 3-year period. Propensity-score matching was performed (537 patients in each group). The mean age and hemoglobin A1c were 58.2 ± 13.0 years and 8.4 ± 1.7%, respectively. There was no significant difference between the dapagliflozin and empagliflozin groups in the risk of MACE (3.7% vs. 4.8%, hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.73-2.35; p = 0.349). Furthermore, there were no differences between the two groups in secondary endpoints including all-cause death, MI, stroke, and hospitalization for HF. Prior MI and history of HF were independent predictors of MACE. Dapagliflozin and empagliflozin showed no significant difference of real-world clinical cardiovascular outcomes in patients with DM over a 3-year period. Further large randomized clinical trials will be warranted for better evaluation.

SGLT-2 inhibitors are associated with lower rates of mortality following myocardial infarction in patients with type 2 diabetes - A SWEDEHEART observational study

Abstract Introduction Secondary prevention following myocardial infarctions is critical in patients with type 2 diabetes due to the substantial risk of adverse events. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce rates of heart failure hospitalisation and cardiovascular death in patients with type 2 diabetes in several randomised studies. We hypothesised that the cardiovascular benefits associated with SGLT2 inhibitors could be observed in patients with diabetes treated with SGLT2 inhibitors following myocardial infarction in a real-world setting. Methods We included all patients with type 2 diabetes with an eGFR &amp;gt;30 ml/min/1.73m2 discharged from the cardiac care unit following a type 1 acute myocardial infarction between 1 January 2018 to 15 February 2022 from the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registries and cross-referenced the registry to the National Prescribed Drug Register. We identified all patients with a redeemed SGLT2 inhibitor 365 days prior to admission or within 10 days after discharge from the cardiac care unit. The primary outcome measure was a composite of all-cause death and hospitalisation for heart failure within 1 year from hospital discharge. Follow-up started at discharge. Results The study included 12,502 patients, of whom 2,770 (22.2%) were treated with SGLT2 inhibitors. Patients who were prescribed SGLT2 inhibitors were younger but had more comorbidities. The primary endpoint occurred in 2,128 (17.0%) patients during the follow-up period. After adjustment for differences in baseline characteristics and medical therapy, the use of SGLT2 inhibitors was associated with a 15% lower rate of the primary outcome, with an adjusted hazard ratio (HR) of 0.85 (95% CI 0.75 – 0.97). This was primarily driven by a lower rate of all-cause mortality, with an adjusted HR of 0.63 (95% CI 0.51 – 0.79). However, no difference was observed in hospitalisations for heart failure, with an adjusted HR of 1.07 (95% CI 0.93 – 1.22). Conclusion Treatment with SGLT2 inhibitors after myocardial infarction in patients with type 2 diabetes was associated with a lower incidence of a composite outcome comprising of all-cause mortality or hospitalisation for heart failure. The lower observed rate appeared to be driven by a lower all-cause mortality rate in those treated with SGLT2 inhibitors.Baseline characteristicsCumulative incidence of the outcome

The effect of SGLT2 inhibitor on clinical outcomes in patients with type 2 diabetes and atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia and represents a significant public health burden with an increased risk of stroke, heart failure (HF) and mortality. Sodium glucose cotransporter 2 (SGLT2) inhibitors improve clinical outcomes in several populations including type 2 diabetes, chronic renal insufficiency, and HF. However, limited data exist on their effects on AF. Purpose We investigated impact of SGLT2 inhibitor on clinical outcomes compared to dipeptidyl peptidase 4 (DPP4) inhibitor among patients with type 2 diabetes and AF. Methods We conducted a retrospective cohort study using the National Health Insurance Service database. A total of 4,771 patients with type 2 diabetes and AF who were newly prescribed SGLT2 inhibitors or DPP4 inhibitors from Jan 2014 to Dec 2019 were selected and matched in a 1:2 ratio by propensity score with 38 confounding variables. We assessed the relationship of SGLT2 inhibitor with clinical outcomes including mortality, stroke, myocardial infarction (MI) and hospitalization for HF compared with DPP4 inhibitor using Cox regression model. Results Over the follow-up, 181 patients (3.7%) died, 121 patients (2.5%) were hospitalized for HF, 95 patients (2.0%) experienced MI, and 293 patients (6.1%) had stroke. Compared to DPP4 inhibitor, SGLT2 inhibitor was associated with lower risk of mortality (HR 0.61; 95% CI 0.39-0.94; P=0.025), but not of MI (HR 1.22 [95% CI 0.71-2.08]; P=0.46) or stroke (HR 1.0 [95% CI 0.75-1.33]; P=0.98). While the incidence of hospitalizations for HF tended to be lower in the SGLT2 inhibitor group, it did not reach a statistical significant level (HR 0.63 [95% CI 0.39-1.02]; P=0.06). Conclusion In a nationwide cohort of patients with type 2 diabetes and AF, SGLT2 inhibitor was associated with a lower risk of mortality compared to DPP4 inhibitor.

THU287 Comparison Of Renal Protective Effects Between SGLT2 Inhibitors And DPP4 Inhibitors In Real-World Clinical Practice

Abstract Disclosure: H. Park: None. S. Park: None. S. Kwon: None. H. Kim: None. D. Byun: None. Recent prospective randomized studies have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors had renal protective effects compared to placebo. In this study, we compared the renal composite outcomes between patients with diabetes treated with SGLT2 inhibitors and those treated with dipeptidyl peptidase 4 (DPP4) inhibitors using real-world clinical data. This retrospective observational study used the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) database at four different university hospitals (Soonchunhyang university hospitals in Seoul, Bucheon, Chunan, and Gumi) in Korea. Subjects prescribed SGLT2 inhibitors or DPP4 inhibitors for at least 90 days were included in the SGLT2 inhibitor or DPP4 inhibitor group, respectively. Subjects prescribed GLP-1 receptor agonist or insulin were excluded in both groups. Renal composite outcomes included a 30% decline in estimated glomerular filtration rate (eGFR) compared to baseline or creatinine doubling or dialysis or death from any cause. After propensity score matching, clinical characteristics in each group at each hospital were well balanced at baseline. Our results from hospitals in Seoul, Bucheon, and Gumi have shown that SGLT2 inhibitor decreased renal composite outcomes compared to DPP4 inhibitor (hazard ratio (HR) 0.644, p=0.020; HR 0.560, p&amp;lt;0.001; HR 0.657, p=0.010, respectively). Furthermore, when all the data were combined, renal composite outcomes were significantly lower in the SGLT2 inhibitor group compared to the DPP4 inhibitor group (HR 0.659, p&amp;lt;0.001). In conclusion, SGLT2 inhibitors effectively reduce renal composite outcomes compared to DPP4 inhibitors in real-world clinical practice. Presentation: Thursday, June 15, 2023

The safety of sodium-glucose co-transporter 2 inhibitors in patients with left ventricular assist device - a single center experience.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are used increasingly for patients with heart failure or chronic kidney disease to improve cardiac and renal outcomes. The use of these medications in patients with left ventricular assist devices (LVAD) is still limited and lacks evidence regarding the safety profile. In this study, we aimed to report our experience in treating 20 patients, supported by LVAD, with SGLT2 inhibitors. We studied the safety profile of SGLT2 inhibitors (dapagliflozin and empagliflozin) in 20 patients (mean age 64.7 ± 12.2 years, 75% male) supported by LVAD as destination therapy. All patients have diabetes mellitus and were prescribed SGLT2 inhibitors for glycemic control. SGLT2 inhibitors were well tolerated with no major adverse events. Few suction events were reported in three patients without the need for pump speed adjustment. There was no change in mean arterial pressure (71.1 ± 5.6 vs. 70.1 ± 4.8 mmHg, P = 0.063). Modest decline in renal function was observed in six patients within the first weeks after drug initiation. There were no events of diabetic ketoacidosis or limb amputation. SGLT2 inhibitors are safe in patients with LVAD and may potentially improve cardiovascular and renal outcomes in this special population.

Prevalence of Sodium Glucose Cotransporter 2 (SGLT-2) Inhibitor Prescribing in Patients with Type 2 Diabetes Mellitus and Reduced Estimated Glomerular Filtration Rate.

Sodium glucose cotransporter 2 (SGLT-2) inhibitors have demonstrated benefit in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), including slowing the progression of CKD and lowering the risk of kidney failure and death. Despite this evidence, literature suggests SGLT-2 inhibitors are underutilized in this population. To assess prescribing practices and identify potential variables predictive of SGLT-2 inhibitor prescribing, a non-interventional, retrospective, cross-sectional study was conducted in patients with T2DM and reduced estimated glomerular filtration rate (eGFR). The primary outcome compared prevalence of SGLT-2 inhibitor prescribing in patients with T2DM and eGFR of 30-44mL/min/1.73m2 to patients with T2DM and eGFR 45-59mL/min/1.73m2. The secondary outcome described possible predictors of prescribing SGLT-2 inhibitors in this population. Of the 9,387 patients identified with T2DM and reduced eGFR, an SGLT-2 inhibitor was prescribed to 324 (12.2%) patients with eGFR of 30-44mL/min/1.73m2 versus 799 (11.9%) patients with eGFR of 45-59mL/min/1.73m2. Patients more likely to be prescribed SGLT-2 inhibitors were younger, male, had a higher body mass index (BMI), a higher hemoglobin A1c (HbA1c), were on other antihyperglycemic medications, had concomitant cardiovascular disease, or had concomitant heart failure. This study found no significant difference in prevalence of SGLT-2 inhibitor prescribing between patients with T2DM and eGFR 30-44mL/min/1.73m2 versus eGFR 45-59mL/min/1.73m2 (p=0.70). Further exploration into the causes of low SGLT-2 inhibitor prescribing prevalence is warranted given the growing evidence supporting the use of these agents in patients with T2DM and reduced renal function.

Prolonged diabetic ketoacidosis due to SGLT2 inhibitor use and low‐carbohydrate diet

AbstractA 59‐year‐old gentleman was admitted with diabetic ketoacidosis (DKA). His medication history included a sodium‐glucose co‐transporter 2 (SGLT2) inhibitor for the past six years. Relevant history includes undertaking a low‐carbohydrate diet for four months.In hospital he required a fixed rate insulin infusion for 25 hours and variable rate insulin infusion for a total of 32 hours to manage his ketonaemia. He received concomitant dextrose infusion and oral nutritional supplements throughout the course of his admission to replenish the likely depleted glycogen stores in his liver as a result of his diet.The case highlights the importance of identifying DKA early and treating the underlying cause. It also highlights the potential increasing prevalence of ketoacidosis which may occur as more patients are prescribed SGLT2 inhibitors and adhere to carbohydrate‐restricted diets. Copyright © 2023 John Wiley &amp; Sons.

Management of Type 2 Diabetic Kidney Disease in 2022: A Narrative Review for Specialists and Primary Care.

Kidney disease is present in almost half of Canadian patients with type 2 diabetes (T2D), and it is also the most common first cardiorenal manifestation of T2D. Despite clear guidelines for testing, opportunities are being missed to identify kidney diseases, and many Canadians are therefore not receiving the best available treatments. This has become even more important given recent clinical trials demonstrating improvements in both kidney and cardiovascular (CV) endpoints with sodium-glucose cotransporter 2 (SGLT2) inhibitors and a nonsteroidal mineralocorticoid receptor antagonist, finerenone. The goal of this document is to provide a narrative review of the current evidence for the treatment of diabetic kidney disease (DKD) that supports this new standard of care and to provide practice points. An expert panel of Canadian clinicians was assembled, including 9 nephrologists, an endocrinologist, and a primary care practitioner. The information the authors used for this review consisted of published clinical trials and guidelines, selected by the authors based on their assessment of their relevance to the questions being answered. Panelists met virtually to discuss potential questions to be answered in the review and agreed on 10 key questions. Two panel members volunteered as co-leads to write the summaries and practice points for each of the identified questions. Summaries and practice points were distributed to the entire author list by email. Through 2 rounds of online voting, a second virtual meeting, and subsequent email correspondence, the authors reached consensus on the contents of the review, including all the practice points. It is critical that DKD be identified as early as possible in the course of the disease to optimally prevent disease progression and associated complications. Patients with diabetes should be routinely screened for DKD with assessments of both urinary albumin and kidney function. Treatment decisions should be individualized based on the risks and benefits, patients' needs and preferences, medication access and cost, and the degree of glucose lowering needed. Patients with DKD should be treated to achieve targets for A1C and blood pressure. Renin-angiotensin-aldosterone system blockade and treatment with SGLT2 inhibitors are also key components of the standard of care to reduce the risk of kidney and CV events for these patients. Finerenone should also be considered to further reduce the risk of CV events and chronic kidney disease progression. Education of patients with diabetes prescribed SGLT2 inhibitors and/or finerenone is an important component of treatment. No formal guideline process was used. The practice points are not graded and are not intended to be viewed as having the weight of a clinical practice guideline or formal consensus statement. However, most practice points are well aligned with current clinical practice guidelines.

Re-examining the widespread policy of stopping sodium-glucose cotransporter-2 inhibitors during acute illness: A perspective based on the updated evidence.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are now seen as an integral part of therapy in type 2 diabetes to control not only blood glucose but to improve cardiovascular and kidney outcomes. Diabetic ketoacidosis (DKA) is an uncommon but serious complication of type 2 diabetes, which has a high case fatality rate. The absolute risk of DKA in large, prospective randomized clinical trials in people with type 2 diabetes using SGLT2 inhibitors has been low, although the relative risk is higher in those assigned to SGLT2 inhibitors compared with placebo. In those without diabetes but prescribed SGLT2 inhibitors for heart failure or chronic kidney disease, the risk of DKA is similar to placebo. Over the course of the COVID-19 pandemic, cases of DKA have also been reported in cases of COVID-19 hospitalizations. Consensus guidelines have recommended that SGLT2 inhibitors should be avoided in cases of serious illness and suggest they are not recommended for routine in-hospital use. However, recent data suggest potential beneficial effects of SGLT2 inhibitors in the setting of acute illness with COVID-19 with no increase in adverse events and low rates of DKA, which were non-severe. Given the low rates of DKA in cardiovascular outcome trials and in hospitalized patients with type 2 diabetes, the potential for SGLT2 inhibitors not being re-initiated following discharge and their cardiovascular and kidney benefits, we believe the practice of routine 'sick day' guidance should be re-examined based on current evidence with a call for further research in this area. Furthermore, high-quality trials of initiation of SGLT2 inhibitors in people admitted to hospital with cardiovascular disease or kidney disease, and trials of continuation of SGLT2 inhibitors in people, with careful monitoring of DKA should be conducted. These should be further supplemented with large observational studies.

The association between sodium-glucose cotransporter 2 inhibitors and incident dementia: A nationwide population-based longitudinal cohort study.

BackgroundThe association of the use of sodium-glucose cotransporter 2 (SGLT2) inhibitor and incident dementia remains unclear. This study aimed to evaluate the risk of incident dementia with the use of SGLT2 inhibitor.MethodsThis is a population-based cohort study utilizing Taiwan’s National Health Insurance Research Database. Each patient who took SGLT2 inhibitors was assigned to the SGLT2 inhibitor group, whereas 1:1 propensity score-matched randomly selected patients who were nonusers of SGLT2 inhibitors were assigned to the non-SGLT2 inhibitor group. The study outcome was incident dementia.ResultsA total of 976,972 patients newly diagnosed with type 2 diabetes mellitus (DM) between 2011 and 2018 were included in this study. After the patients’ propensity score matching by age, sex, duration of DM, comorbidities and drug index date of the patients, a total of 103,247 patients in the SGLT2 inhibitor group and 103,247 in the non-SGLT2 inhibitor group were enrolled for analysis. The SGLT2 inhibitor group was associated with a lower risk of incident dementia (adjusted hazard ratio: 0.89, 95% confidence interval: 0.82–0.96; p = .0021). Diabetic complications were significantly lower in the SGLT2 inhibitor group compared with the non-SGLT2 group. Sensitivity analysis was also consistent with the main analysis.ConclusionsPatients with type 2 DM who were prescribed SGLT2 inhibitors were associated with a lower risk of incident dementia compared with those not prescribed SGLT2 inhibitors in real-world practice.

Identifying Barriers To SGLT2 Inhibitor Use In Eligible Patients With Heart Failure: A Real-world Experience From A Single Centre

Background Recent landmark trials investigating the use of sodium glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure (HF) with reduced ejection fraction (HFrEF) have demonstrated significant reductions in cardiovascular mortality and heart failure hospitalization. As a result of these trials, recent updates to major societal guidelines have included a strong recommendation for the initiation of SGLT2 inhibitors in patients with HFrEF and HF symptoms. The routine initiation of SGLT2 inhibitors in eligible patients, however, has been limited by several factors including cost, increased pill burden, concomitant chronic kidney disease and adverse effects, among others. Real-world data investigating the use of SGLT2 inhibitors and perceived barriers to their initiation in eligible heart failure patients are currently lacking. Methods/Results This is a prospective, single center, observational study evaluating the use of SGLT2 inhibitors in a specialized heart function clinic. Patients seen in clinic from January 1, 2021 to April 30, 2021 were screened for eligibility of SGLT2 inhibitor initiation. Patient characteristics, background medical therapy and lab values of interest were recorded using paper charts and local electronic records. Providers were asked to record whether SGLT2 inhibitor therapy was successfully initiated and if not, the reason it was not prescribed. In total 286 of 496 (57.7%) patients screened were eligible for SGLT2 inhibitor therapy. Among eligible patients, average age was 63.0 years (SD +/- 13.5); 217 patients were male (75.9%) and 69 female (24.1%); 17 (5.9%) were NYHA class 1, 220 (76.9%) were NYHA class 2, 47 (16.4%) were NYHA class 3 and 2 (0.7%) were NYHA class 4. In total 113/286 eligible patients were prescribed SGLT2 inhibitors (39.5%). Of these 286 eligible patients, 265 had HFrEF, of which 101 were prescribed an SGLT2 inhibitor (38.1%). The most common reasons for not prescribing SGLT2 inhibitor therapy included: up-titration or initiation of other medications/defer to future visit in 110 patients (63.6%), patient preference or refusal in 15 patients (8.7%) and inability to afford the cost of medication in 11 patients (6.4%). Conclusion A substantial proportion (57.7%) of HF patients are eligible for an SGLT2 inhibitor. However, SGLT2 inhibitors are currently underutilized in eligible patients seen in a specialized heart function clinic predominantly due to up-titration or initiation of other HF therapies. Strategies should be undertaken to increase utilization of this new class of therapy for HF to reduce cardiovascular events. Recent landmark trials investigating the use of sodium glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure (HF) with reduced ejection fraction (HFrEF) have demonstrated significant reductions in cardiovascular mortality and heart failure hospitalization. As a result of these trials, recent updates to major societal guidelines have included a strong recommendation for the initiation of SGLT2 inhibitors in patients with HFrEF and HF symptoms. The routine initiation of SGLT2 inhibitors in eligible patients, however, has been limited by several factors including cost, increased pill burden, concomitant chronic kidney disease and adverse effects, among others. Real-world data investigating the use of SGLT2 inhibitors and perceived barriers to their initiation in eligible heart failure patients are currently lacking. This is a prospective, single center, observational study evaluating the use of SGLT2 inhibitors in a specialized heart function clinic. Patients seen in clinic from January 1, 2021 to April 30, 2021 were screened for eligibility of SGLT2 inhibitor initiation. Patient characteristics, background medical therapy and lab values of interest were recorded using paper charts and local electronic records. Providers were asked to record whether SGLT2 inhibitor therapy was successfully initiated and if not, the reason it was not prescribed. In total 286 of 496 (57.7%) patients screened were eligible for SGLT2 inhibitor therapy. Among eligible patients, average age was 63.0 years (SD +/- 13.5); 217 patients were male (75.9%) and 69 female (24.1%); 17 (5.9%) were NYHA class 1, 220 (76.9%) were NYHA class 2, 47 (16.4%) were NYHA class 3 and 2 (0.7%) were NYHA class 4. In total 113/286 eligible patients were prescribed SGLT2 inhibitors (39.5%). Of these 286 eligible patients, 265 had HFrEF, of which 101 were prescribed an SGLT2 inhibitor (38.1%). The most common reasons for not prescribing SGLT2 inhibitor therapy included: up-titration or initiation of other medications/defer to future visit in 110 patients (63.6%), patient preference or refusal in 15 patients (8.7%) and inability to afford the cost of medication in 11 patients (6.4%). A substantial proportion (57.7%) of HF patients are eligible for an SGLT2 inhibitor. However, SGLT2 inhibitors are currently underutilized in eligible patients seen in a specialized heart function clinic predominantly due to up-titration or initiation of other HF therapies. Strategies should be undertaken to increase utilization of this new class of therapy for HF to reduce cardiovascular events.

Comparative Safety of Sodium-Glucose Cotransporter 2 Inhibitors Versus Dipeptidyl Peptidase 4 Inhibitors and Sulfonylureas on the Risk of Diabetic Ketoacidosis.

To assess the association of sodium-glucose cotransporter 2 (SGLT2) inhibitors with diabetic ketoacidosis compared with dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas in patients with type 2 diabetes. We conducted a new-user active comparator cohort study to examine two pairwise comparisons: 1) SGLT2 inhibitors versus DPP-4 inhibitors and 2) SGLT2 inhibitors versus sulfonylureas. The main outcome was diabetic ketoacidosis present on hospital admission. We adjusted for confounders through propensity score matching. We used Cox proportional hazards regression with a robust variance estimator to estimate hazard ratios (HRs) and corresponding 95% CIs while adjusting for calendar time. In cohort 1 (n = 85,125 for SGLT2 inhibitors and n = 85,125 for DPP-4 inhibitors), the incidence rates of diabetic ketoacidosis per 1,000 person-years were 6.0 and 4.3 for SGLT2 inhibitors and DPP4 inhibitors, respectively. In cohort 2 (n = 72,436 for SGLT2 inhibitors and n = 72,436 for sulfonylureas), the incidence rates of diabetic ketoacidosis per 1,000 person-years were 6.3 and 4.5 for SGLT2 inhibitors and sulfonylureas, respectively. In Cox proportional hazards regression models, the use of SGLT2 inhibitors was associated with a higher rate of diabetic ketoacidosis compared with DPP-4 inhibitors (adjusted HR [aHR] 1.63; 95% CI 1.36, 1.96) and sulfonylureas (aHR 1.56; 95% CI 1.30, 1.87). In this comparative safety study using real-world data, patients with type 2 diabetes who were newly prescribed SGLT2 inhibitors had a higher rate of diabetic ketoacidosis compared with DPP-4 inhibitors and sulfonylureas. Clinicians should be vigilant about this association.

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.

IDENTIFYING BARRIERS TO SGLT2 INHIBITOR USE IN ELIGIBLE PATIENTS WITH HEART FAILURE: A REAL-WORLD EXPERIENCE FROM A SINGLE CENTRE

<h3>BACKGROUND</h3> Recent landmark trials investigating the use of sodium glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure (HF) with reduced ejection fraction (HFrEF) have demonstrated significant reductions in cardiovascular mortality and heart failure hospitalization. As a result of these trials, the Canadian Cardiovascular Society (CCS) has recently published a guideline update strongly recommending the initiation of SGLT2 inhibitors in patients with HFrEF and HF symptoms. The routine initiation of SGLT2 inhibitors in eligible patients, however, has been limited by several factors including cost, increased pill burden, concomitant chronic kidney disease and adverse effects, among others. Canadian real-world data investigating the use of SGLT2 inhibitors and perceived barriers to their initiation in eligible heart failure patients are currently lacking. <h3>METHODS AND RESULTS</h3> This is a prospective, single center, observational study evaluating the use of SGLT2 inhibitors in a specialized heart function clinic. Patients seen in clinic from January 1, 2021 to Mar 31, 2021 were screened for eligibility of SGLT2 inhibitor initiation. Patient characteristics, background medical therapy and lab values of interest were recorded using paper charts and local electronic records. Providers were asked to record whether SGLT2 inhibitor therapy was successfully initiated and if not, the reason it was not prescribed. In total, 258 of 384 (67%) patients screened were eligible for SGLT2 inhibitor therapy. Among eligible patients, average age was 63.1 years (SD +/- 13.7); 197 patients were male (76.4%) and 61 female (23.6%); 14 (5.4%) were NYHA class 1, 200 (77.5%) were NYHA class 2, 42 (16.3%) were NYHA class 3 and 2 (0.8%) were NYHA class 4. In total 104/258 eligible patients were prescribed SGLT2 inhibitors (40.3%). The most common reasons for not prescribing SGLT2 inhibitor therapy included: up-titration or initiation of other medications/defer to future visit in 97 patients (63.0%), patient preference or refusal in 13 patients (8.4%) and inability to afford the cost of medication in 11 patients (7.1%). <h3>CONCLUSION</h3> A substantial proportion (67%) of HF patients are eligible for an SGLT2 inhibitor. However, SGLT2 inhibitors are currently underutilized in eligible patients seen in a specialized heart function clinic predominantly due to up-titration or initiation of other HF therapies. Strategies should be undertaken to increase utilization of this new class of therapy for HF to reduce cardiovascular events.

On-label use of sodium-glucose cotransporter2 inhibitors might increase the risk of diabetic ketoacidosis in patients with type1 diabetes.

Aims/IntroductionThis study aimed to investigate the risk of diabetic ketoacidosis (DKA) in insulin‐treated type 1 diabetes patients administered sodium–glucose cotransporter 2 (SGLT2) inhibitors in real‐world clinical practice.Materials and MethodsWe carried out a real‐world, retrospective, observational cohort study using Japanese Medical Data Vision, a diagnosis procedure combination database. We identified insulin‐treated adult type 1 diabetes patients enrolled from December 2018 to October 2019. We assessed the incidence and risk of DKA in type 1 diabetes patients using SGLT2 inhibitors in an ‘on‐label’ manner. Cox multivariate regression analyses were carried out to determine clinical factors linked to SGLT2 inhibitor‐associated DKA.ResultsOf 11,475 type 1 diabetes patients, 1,898 (16.5%) were prescribed SGLT2 inhibitors. DKA occurred in 139 (7.3%) of these patients, with 20.2 incidences per 100 person‐years. These patients also showed significantly higher DKA rates than did those not receiving SGLT2 inhibitors (hazard ratio 1.66, 95% confidence interval 1.33–2.06; P < 0.001). The mean time until DKA onset in SGLT2 inhibitor‐treated type 1 diabetes patients was 30.6 ± 30.1 days. The risk of SGLT2 inhibitor‐associated DKA increased in type 1 diabetes patients irrespective of sex, age or body mass index. However, the risk did not increase in type 1 diabetes patients receiving continuous subcutaneous insulin infusion, which warrants further investigation because of the small number of type 1 diabetes patients receiving continuous subcutaneous insulin infusion.Conclusions‘On‐label’ SGLT2 inhibitor use might increase DKA risk among insulin‐treated type 1 diabetes patients irrespective of sex, age or body mass index. Both type 1 diabetes patients and healthcare providers should be wary of DKA, especially during the first month of initiating SGLT2 inhibitors.

Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: A population-based retrospective cohort study.

Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID‐19, when compared with an active comparator. We performed a propensity‐score‐matched cohort study with active comparators and a negative control outcome in a large UK‐based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase‐4 (DPP‐4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID‐19. The incidence rate of COVID‐19 was 19.7/1000 person‐years among users of SGLT2 inhibitors and 24.7/1000 person‐years among propensity‐score‐matched users of DPP‐4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID‐19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP‐4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID‐19 pandemic.

Poor adherence and persistence to sodium glucose co-transporter 2 inhibitors in real-world settings: Evidence from a systematic review and meta-analysis.

Despite increasing prescription of sodium glucose co-transporter 2 (SGLT2) inhibitors, there is limited insight of the patterns of use among patients with diabetes prescribed these drugs. This study aimed to summarize available real-world data on the adherence and persistence to SGLT2 inhibitors. A systematic review for observational studies reporting the adherence and persistence to SGLT2 inhibitors was performed in Medline, Embase, and Web of Science from their inception to October 2019. Data were analysed via random-effects meta-analysis. A total of 22 studies (31 cohorts) comprising 123 854 individuals prescribed SGLT2 inhibitors from eight countries were included. The pooled mean proportions of days covered [PDC] at six months and one year were 0.77 (95% confidence interval [CI] 0.72-0.82) and 0.72 (95% CI 0.66-0.77), respectively. The pooled proportions adherent (PDC ≥0.80) at six months and one year were 59.5% (95% CI 52.9-65.9) and 49.0% (95% CI 42.3-55.8), respectively. The pooled proportions of people persistent at six months, one year, and two years were 80.1% (95% CI 75.8-84.0), 61.8% (95% CI 57.8-65.7), and 45.9% (95% CI 35.5-56.5), respectively. When persistence was defined as the absence of ≥90-days gap, the equivalent pooled proportions persistent were 81.5% (95% CI 73.1-88.6), 58.9% (95% CI 53.1-64.6), and 34.7% (95% CI 33.6-35.8). Adherence and persistence appeared to vary across different SGLT2 inhibitors. Real-world adherence and persistence to SGLT2 inhibitors is poor. Hence, targets for improving treatment adherence and persistence need to be identified and appropriate interventions implemented.