Search

Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve health status in heart failure (HF) across the left ejection fraction ejection spectrum. However, the effects of SGLT1 and SGLT2 inhibition on health status are unknown. These prespecified analyses of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trial examined the effects of sotagliflozin vs placebo on HF-related health status. SOLOIST-WHF randomized patients hospitalized or recently discharged after a worsening HF episode to receive sotagliflozin or placebo. The primary endpoint was total number of HF hospitalizations, urgent HF visits, and cardiovascular death. Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) score was a prespecified secondary endpoint. This analysis evaluated change in the KCCQ-12 score from baseline to month 4. Of 1,222 patients randomized, 1,113 (91%) had complete KCCQ-12 data at baseline and 4 months. The baseline KCCQ-12 score was low overall (median: 41.7; Q1-Q3: 27.1-58.3) and improved by 4 months in both groups. Sotagliflozin vs placebo reduced the risk of the primary endpoint consistently across KCCQ-12 tertiles (P trend = 0.54). Sotagliflozin-treated patients vs those receiving placebo experienced modest improvement in KCCQ-12 at 4 months (adjusted mean change: 4.1 points; 95% CI: 1.3-7.0 points; P = 0.005). KCCQ-12 improvements were consistent across prespecified subgroups, including left ventricular ejection fraction <50% or ≥50%. More patients receiving sotagliflozin vs those receiving placebo had at least small (≥5 points) improvements in KCCQ-12 at 4 months (OR: 1.38; 95% CI: 1.06-1.80; P = 0.017). Sotagliflozin improved symptoms, physical limitations, and quality of life within 4 months after worsening HF, with consistent benefits across baseline demographic and clinical characteristics. (Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure [SOLOIST-WHF]; NCT03521934) [ABSTRACT FROM AUTHOR]

Importance Objective Design, Setting and Participants Exposures Main Outcomes and Measures Results Conclusion and Relevance Diabetes increases the risk of Parkinson disease (PD). Sodium‐glucose cotransporter 2 (SGLT2) inhibitors, a new glucose‐lowering therapeutic class, have shown neuroprotective effects in mechanistic studies. However, the association between SGLT2 inhibitors and PD risk in real‐world populations with type 2 diabetes (T2D) remains unclear.The aim was to assess the association between SGLT2 inhibitors and the risk of PD in older populations with T2D.This retrospective cohort analysis used Medicare claims data from 2016 to 2020 to identify fee‐for‐service beneficiaries ≥65 years diagnosed with T2D and without pre‐existing PD.The initiation of an SGLT2 inhibitor was compared with that of a dipeptidyl peptidase‐4 (DPP4) inhibitor.The outcome was the first incident PD ever since the date initiating either an SGLT2 inhibitor or a DPP4 inhibitor. We employed a 1:1 propensity score matching to balance the baseline covariates between treatment groups, including sociodemographics, comorbidities and co‐medications. We applied Cox regression models to assess the effect of SGLT2 inhibitors versus DPP4 inhibitors on incident PD.Of 89 330 eligible Medicare beneficiaries (mean age: 75 ± 7 years, 52% women), 0.6% (n = 537) had incident PD over the follow‐up. After 1:1 propensity matching, the PD incidence was 2.5 and 3.5 events per 1000 person‐years in the SGLT2 inhibitor group and DPP4 inhibitor group, respectively. The SGLT2 inhibitor group was associated with a significantly lower risk of incident PD than the DPP4 inhibitor group (hazard ratio: 0.70 [95% confidence interval: 0.55–0.89]). There is a potential trend that the risk reduction in incident PD was profound in non‐Hispanic Black individuals and insulin users.Compared to DPP4 inhibitors, SGLT2 inhibitors were associated with a significantly lower risk of incident PD in older populations with T2D. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on cardiovascular and cerebrovascular diseases. Methods: Articles of SGLT2i on cardiovascular and cerebrovascular diseases were searched. Two authors independently screened the literature, extracted the data, assessed the quality of the study and performed statistical analyses using Review Manager 5.4. Results: Random-effect model was used to merge the OR values, and the pooled effect showed that SGLT2i had significant preventive effects on cardiovascular death (OR=0.76, 95%CI 0.64 to 0.89), myocardial infarction (OR=0.90, 95%CI 0.84 to 0.96), heart failure (OR=0.69, 95%CI 0.64 to 0.74) and all-cause mortality (OR=0.65, 95%CI 0.58 to 0.73). Empagliflozin, dapagliflozin and canagliflozin all reduced the incidence of heart failure (OR=0.72, 95%CI 0.64 to 0.82; OR=0.56, 95%CI 0.39 to 0.80; OR=0.62, 95%CI 0.53 to 0.73), but only dapagliflozin displayed a favorable effect on inhibiting stroke (OR=0.78, 95%CI 0.63 to 0.98). SGLT2i could prevent stroke (OR=0.86, 95%CI 0.75 to 0.99), heart failure (OR=0.63, 95%CI 0.56 to 0.70) and all-cause mortality (OR=0.64, 95%CI 0.57 to 0.72) compared to DPP-4i. Furthermore, SGLT2i could reduce the incidence of heart failure (OR=0.72, 95%CI 0.67 to 0.77) and cardiovascular death (OR=0.72, 95%CI 0.54 to 0.95) in patients with high-risk factors. Conclusions: SGLT2i affects cardiovascular death, myocardial infarction, heart failure and all-cause mortality. Only dapagliflozin displayed a favorable effect on inhibiting stroke. SGLT2i could prevent stroke, heart failure and all-cause mortality compared to DPP-4i. In addition, SGLT2i significantly reduced the development of heart failure and cardiovascular death in patients with high-risk factors. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have demonstrated associations with lowering cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the impact of SGLT-2is on individuals at dialysis commencement remains unclear. The aim of this real-world study is to study the association between SGLT-2is and outcomes in patients with T2DM at dialysis commencement. Methods: This is a retrospective cohort study of electronic health records (EHRs) of patients with T2DM from TriNetX Research Network database between January 1, 2012, and January 1, 2024. New-users using intention to treatment design was employed and propensity score matching was utilized to select the cohort. Clinical outcomes included major adverse cardiac events (MACE) and all-cause mortality. Safety outcomes using ICD-10 codes, ketoacidosis, urinary tract infection (UTI) or genital infection, dehydration, bone fracture, below-knee amputation, hypoglycemia, and achieving dialysis-free status at 90 days and 90-day readmission. Results: Of 49,762 patients with T2DM who initiated dialysis for evaluation, a mere 1.57% of patients utilized SGLT-2is within 3 months after dialysis. 771 SGLT-2i users (age 63.3 ± 12.3 years, male 65.1%) were matched with 771 non-users (age 63.1 ± 12.9 years, male 65.8%). After a median follow-up of 2.0 (IQR 0.3–3.9) years, SGLT-2i users were associated with a lower risk of MACE (adjusted Hazard Ratio [aHR] = 0.52, p value < 0.001), all-cause mortality (aHR = 0.49, p < 0.001). SGLT-2i users were more likely to become dialysis-free 90 days after the index date (aHR = 0.49, p < 0.001). No significant differences were observed in the incidence of ketoacidosis, UTI or genital infection, hypoglycemia, dehydration, bone fractures, below-knee amputations, or 90-day readmissions. Conclusions: Our findings indicated a lower incidence of all-cause mortality and MACE after long-term follow-up, along with a higher likelihood of achieving dialysis-free status at 90 days in SGLT-2i users. Importantly, they underscored the potential cardiovascular protection and safety of SGLT-2is use in T2DM patients at the onset of dialysis. [ABSTRACT FROM AUTHOR]

This article explores the use of sodium-glucose co-transporter-2 (SGLT-2) inhibitors in the treatment of type 2 diabetes, chronic kidney disease, and chronic heart failure. While these inhibitors have been recommended in treatment guidelines, there is still a disconnect between scientific consensus and clinical practice, resulting in many eligible patients not receiving these medications. The article emphasizes the importance of accurately prescribing SGLT-2 inhibitors and having meaningful conversations with patients about treatment goals and potential side effects. It also highlights the need for more research and education to bridge the gap between clinical trials and real-world use of these drugs. [Extracted from the article]

Objectives Materials and Methods Results Conclusion To investigate the utilization and costs of non‐insulin glucose‐lowering drugs (GLDs) in Australia from 2013 to 2023.We conducted a retrospective analysis of the Australian Pharmaceutical Benefits Scheme (PBS) administrative dataset of 118 727 494 GLD prescriptions. The main outcome measures were the annual number of GLD prescriptions dispensed, accounting for type 2 diabetes mellitus (T2DM) prevalence and healthcare system costs, adjusted for inflation.Utilization of GLDs doubled from 6.4 million prescriptions in 2013 to 15.6 million in 2023. The average annual percent increase in utilization was 8.1%, compared to the average annual increase in prevalence of T2DM of 1.8%. The biggest change was in sodium‐glucose cotransporter‐2 (SGLT2) inhibitors, for which there was an average annual increase in utilization of 59.4% (95% confidence interval [CI] 51.7%, 68.2%; p < 0.05) from 2014 (first full year of PBS listing), followed by glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), which showed an increase of 31.4% (95% CI 28.5%, 33.8%; p < 0.05) annually (2013 to 2023). Dipeptidyl peptidase‐4 inhibitor utilization tripled, with an average annual increase of 10.9% (95% CI 8.1%, 13.8%; p < 0.05), but this plateaued from 2020. Metformin utilization increased by 4.7% (95% CI 2.0%, 6.9%; p < 0.05) annually. In contrast, sulphonylurea, glitazone and acarbose utilization declined. Total GLD costs increased threefold over the same period. Despite only accounting for 11.7% of utilization, GLP‐1RAs contributed to 35% of the costs.Utilization of GLDs doubled, and associated costs tripled over the past 11 years, with no sign of either utilization or costs plateauing, predominantly due to increased GLP‐1RA and SGLT2 inhibitor prescribing. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The aim of this study was to examine contemporary trends in the use of, time to, and type of first add‐on anti‐hyperglycaemic therapy to metformin in Australia.We used the dispensing records of a 10% random sample of Pharmaceutical Benefits Scheme (PBS) eligible people. We included people aged 40 years and older initiating metformin from 1 January 2018 to 31 December 2020. Our primary outcome was first add‐on anti‐hyperglycaemic medicine within 2 years of metformin initiation. We analysed time to dispensing of first add‐on therapy. All analyses were stratified by metformin initiation year.Overall, 38 747 people aged 40 years and older initiated metformin between 2018 and 2020. Approximately one‐third (n = 12 946) of people received add‐on therapy with the proportion increasing slightly by year of metformin initiation (32.3% in 2018 to 34.8% in 2020). Amongst people with add‐on therapy following metformin initiation, sodium‐glucose cotransporter 2 inhibitor (SGLT2i) use increased from 28.8% (2018) to 35.0% (2020), and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) increased from 3.0% to 9.6%, respectively. Dipeptidyl peptidase‐4 inhibitors and sulfonylureas as first add‐on therapy decreased and insulin remained stable. One‐third of people with add‐on therapy initiated the therapy on the same day metformin was initiated, i.e. initial combination therapy.Amongst people initiating metformin from 2018 to 2020, there was an increasing proportion of SGLT2i and GLP‐1 RA being used as first add‐on therapy. However, the overall prevalence of add‐on therapy was low. Advocacy to promote add‐on therapy with cardiorenal beneficial medicines is critical to reduce type 2 diabetes morbidity and mortality. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head clinical trials. The aim of this study was to compare the cardiovascular effectiveness of SGLT2is, GLP-1 RAs, dipeptidyl peptidase-4 inhibitors (DPP4is), and clinical sulfonylureas (SUs) as second-line antihyperglycemic agents in T2DM. Across the LEGEND-T2DM (Large-Scale Evidence Generation and Evaluation Across a Network of Databases for Type 2 Diabetes Mellitus) network, 10 federated international data sources were included, spanning 1992 to 2021. In total, 1,492,855 patients with T2DM and cardiovascular disease (CVD) on metformin monotherapy were identified who initiated 1 of 4 second-line agents (SGLT2is, GLP-1 RAs, DPP4is, or SUs). Large-scale propensity score models were used to conduct an active-comparator target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, on-treatment Cox proportional hazards models were fit for 3-point MACE (myocardial infarction, stroke, and death) and 4-point MACE (3-point MACE plus heart failure hospitalization) risk and HR estimates were combined using random-effects meta-analysis. Over 5.2 million patient-years of follow-up and 489 million patient-days of time at risk, patients experienced 25,982 3-point MACE and 41,447 4-point MACE. SGLT2is and GLP-1 RAs were associated with lower 3-point MACE risk than DPP4is (HR: 0.89 [95% CI: 0.79-1.00] and 0.83 [95% CI: 0.70-0.98]) and SUs (HR: 0.76 [95% CI: 0.65-0.89] and 0.72 [95% CI: 0.58-0.88]). DPP4is were associated with lower 3-point MACE risk than SUs (HR: 0.87; 95% CI: 0.79-0.95). The pattern for 3-point MACE was also observed for the 4-point MACE outcome. There were no significant differences between SGLT2is and GLP-1 RAs for 3-point or 4-point MACE (HR: 1.06 [95% CI: 0.96-1.17] and 1.05 [95% CI: 0.97-1.13]). In patients with T2DM and CVD, comparable cardiovascular risk reduction was found with SGLT2is and GLP-1 RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of SGLT2is and GLP-1 RAs should be prioritized as second-line agents in those with established CVD. [ABSTRACT FROM AUTHOR]

Objective: Diabetes-related care makes up approximately 24% of outpatient clinic visits. Therefore, confidence and understanding of diabetes management is necessary for family medicine residents. Methods: We developed a combined lecture and simulation lab curriculum utilizing a registered nurse and pharmacist to deliver education to 20 family medicine learners. Pre and post surveys of the educational material were completed in 2 sections including one gauging medical knowledge and a second part gauging level of comfort. Results: Of the learners who participated, fourteen completed the pre-post surveys. Most (53%) respondents improved their scores, while 20% scored the same 27% scored worse. The overall average score increased 57% to 70% and improvement was statistically significant (P <.05). All learners improved confidence by at least 1 point. Conclusion: An interprofessional team utilizing a lecture curriculum focusing on providing education on effective prescribing, medication safety profiles, and resource availability, showed improvement in confidence but mixed knowledge benefit. Further modifications to the curriculum may yield further educational gains. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Patients with type 2 diabetes (T2D) are at high risk for developing chronic kidney disease (CKD). The onset of incident CKD may complicate glycemic control among these patients. This study aimed to characterize antihyperglycemic medication use after incident CKD onset among patients with T2D to inform disease management. STUDY DESIGN: Retrospective cohort study. METHODS: Patients with incident CKD and prior T2D were identified from the Optum electronic health records database between March 2013 and September 2021. Patterns of antihyperglycemic use were assessed during the 1-year baseline period and after incident CKD diagnosis and described by baseline hemoglobin A1C (HbA1C) level (controlled [< 7%] vs elevated [≥ 7%]) and CKD severity. RESULTS: The study consisted of 262,395 patients, of whom 51% had elevated HbA1C. After CKD onset, 23.9% of patients initiated new antihyperglycemics within 1 year. Patients with elevated HbA1C had shorter time to new treatment initiation compared with those with controlled HbA1C (median, 28.7 vs 83.7 months). Patients with elevated urine albumin-to-creatinine ratio (uACR) had shorter median time to new treatment initiation (39.9-42.4 months) than those with normal uACR (59.8 months). Less than 7% of patients with stage 3 CKD and even smaller percentages of patients with higher stages of CKD utilized glucagon-like peptide1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. CONCLUSIONS: Treatment of T2D was considerably heterogenous by HbA1C level and CKD severity in patients with incident CKD. Current agents may not sufficiently fulfill the unmet need of T2D management in patients with CKD. [ABSTRACT FROM AUTHOR]

Background: Sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) are novel agents for heart failure (HF) and are now recommended in guidelines. Understanding general physicians' perspectives can help to optimise utilisation of this new medication. Aim: To understand the clinical concerns and barriers from general physicians about prescribing SGLT2is in a general medicine cohort. Methods: A questionnaire exploring clinicians' experience, comfort level and barriers to prescribing SGLT2is in patients with HF, incorporating two clinical scenarios, was disseminated to Internal Medicine Society of Australia and New Zealand members over a 2‐month period. Results: Ninety‐eight participants responded to the questionnaire (10.8% response rate). Most respondents (66.3%) were senior medical staff. Most participants worked in metropolitan settings (64.3%) and in public hospital settings (83.7%). For HF with reduced ejection fraction, 23.5% of participants reported prescribing SGLT2is frequently (defined as prescribing SGLT2is frequently over 75% of occasions). For HF with preserved ejection fraction, 57.1% of participants reported prescribing SGLT2is less than 25% of the time. Almost half of the participants (44%) expressed a high level of familiarity with therapeutic knowledge of SGLT2is, while 47% indicated high familiarity with potential side effects. Patient complexity, cost of medications and discontinuity of care were identified as important barriers. Euglycemic diabetic ketoacidosis was the side effect that caused the most hesitancy to prescribe SGLT2is in 48% of the respondents. Conclusion: General physicians in Australia and Aotearoa New Zealand are familiar with the therapeutic knowledge and side effects of SGLT2is. Patient complexity, medication cost and discontinuity of care were significant barriers to the use of SGLT2is for HF among general physicians. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the prevalence of inappropriate tight glycemic control in older adults with type 2 diabetes and other chronic conditions in New York City, and to identify factors associated with this practice. Methods: We conducted a retrospective cohort study using the INSIGHT Clinical Research Network. The study population included 11,728 and 15,196 older adults in New York City (age ≥ 75 years) with a diagnosis of type 2 diabetes, and at least one other chronic medical condition, in 2017 and 2022, respectively. The main outcome of interest was inappropriate tight glycemic control, defined as HbA1c <7.0% (<53 mmol/mol) with prescription of at least one high‐risk agent (insulin or insulin secretagogue). Results: The proportion of older adults with inappropriate tight glycemic control decreased by nearly 19% over a five‐year period (19.4% in 2017 to 15.8% in 2022). There was a significant decrease in insulin (27.8% in 2017; 24.3% in 2022) and sulfonylurea (29.4% in 2017; 21.7% in 2022) medication prescription, and increase in use of GLP‐1 agonists (1.8% in 2017; 11.4% in 2022) and SGLT‐2 inhibitors (5.8% in 2017; 25.1% in 2022), among the total population. Factors associated with inappropriate tight glycemic control in 2022 included history of heart failure (adjusted odds ratio [aOR] 1.38), chronic kidney disease ([aOR] 1.93), colorectal cancer ([aOR] 1.38), acute myocardial infarction ([aOR] 1.28), "other" ([aOR] 0.72) or "unknown" ([aOR] 0.72) race, and a point increase in BMI ([aOR] 0.98). Conclusions: We found an encouraging trend toward less use of high‐risk medication strategies for older adults with type 2 diabetes and multiple chronic conditions. However, one in six patients in 2022 still had inappropriate tight glycemic control, indicating a need for continued efforts to optimize diabetes management in this population. [ABSTRACT FROM AUTHOR]

The article discusses a 2024 retrospective study on risk factors for hospitalized urinary tract infections (UTI) among new users of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in nursing homes (NH). Results show that female sex, UTI history, and catheter use were risk factors. Also noted is the need for caution in SGLT2is prescriptions to multimorbid older patients, specially for females with UTI or catheter use history to avoid hospitalizations.

Aims: The aim of this work is to compare empagliflozin systemic exposure between patients with heart failure (HF) and patients with type 2 diabetes (T2D). Methods: Analysis of covariance (ANCOVA) compared steady state trough concentrations of empagliflozin 10 mg in EMPEROR‐reduced (patients with HF with reduced ejection fraction [HFrEF]) and EMPA‐REG OUTCOME (patients with T2D at high cardiovascular risk) after adjusting for eGFR and body weight. Results: The difference in geometric Mean (gMean) empagliflozin steady state trough concentration of 10 mg empagliflozin between EMPEROR‐reduced and EMPA‐REG OUTCOME was 1.47‐fold (95% confidence interval [CI]: 1.33, 1.63). Additionally, ANCOVA for the sub‐group of patients with both T2D and HF conditions revealed a difference in gMean steady state trough concentration of 1.53‐fold (95% CI: 1.26, 1.85). In both patients with HFrEF and HF with preserved EF (HFpEF), there was no major difference in empagliflozin steady state trough exposure by New York Heart Association (NYHA) classification or by use of angiotensin receptor‐neprilysin inhibitor as comedication. A weak positive correlation was observed for NT‐proBNP at Week 12 and empagliflozin steady state trough concentration in both patients with HFrEF and HFpEF (Pearson correlation r = 0.19). Conclusions: Plasma concentrations of empagliflozin in patients with HF were higher compared to patients with T2D, but the exposure resulting from the 10 mg dose was still below the exposure resulting from the dose of 25 mg approved in patients with T2D. The difference in exposure was attributable to demographic characteristics and HF‐induced pathophysiological changes. Overall, the results confirm 10 mg as the appropriate empagliflozin dose in patients with HF. [ABSTRACT FROM AUTHOR]

Objective: To compare the risks of gastric cancer and other gastric diseases in patients with type-2 diabetes mellitus (T2DM) exposed to sodium-glucose cotransporter 2 inhibitors (SGLT2I), dipeptidyl peptidase-4 inhibitors (DPP4I) or glucagon-like peptide-1 receptor agonists (GLP1a). Design: This was a population-based cohort study of prospectively collected data on patients with T2DM prescribed SGLT2I, DPP4I or GLP1a between January 1st 2015 and December 31st 2020 from Hong Kong. The outcomes were new-onset gastric cancer, peptic ulcer (PU), acute gastritis, non-acute gastritis, and gastroesophageal reflux disease (GERD). Propensity score matching (1:1) using the nearest neighbour search was performed, and multivariable Cox regression was applied. A three-arm comparison between SGLT2I, DPP4I and GLP1a was conducted using propensity scores with inverse probability of treatment weighting. Results: A total of 62,858 patients (median age: 62.2 years old [SD: 12.8]; 55.93% males; SGLT2I: n = 23,442; DPP4I: n = 39,416) were included. In the matched cohort, the incidence of gastric cancer was lower in SGLT2I (Incidence rate per 1000 person-year, IR: 0.32; 95% confidence interval, CI 0.23–0.43) than in DPP4I (IR per 1000 person-year: 1.22; CI 1.03–1.42) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of gastric cancer (HR 0.30; 95% CI 0.19–0.48), PU, acute gastritis, non-acute gastritis, and GERD (p < 0.05) compared to DPP4I use. In the three-arm analysis, GLP1a use was associated with higher risks of gastric cancer and GERD compared to SGLT2I use. Conclusions: The use of SGLT2I was associated with lower risks of new-onset gastric cancer, PU, acute gastritis, non-acute gastritis, and GERD after matching and adjustments compared to DPP4I use. SGLT2I use was associated with lower risks of GERD and gastric cancer compared to GLP1a use. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted in Germany that examines the relationship between regional socioeconomic factors and the use of certain medications for adults with type 2 diabetes. The study finds that individuals in socioeconomically disadvantaged areas have lower access to newer glucose-lowering medications, such as SGLT2 inhibitors and GLP-1RAs. This disparity in access may contribute to socioeconomic disparities in cardiovascular health outcomes. The study suggests that further investigation into structural factors is needed to address these disparities. The study also highlights the importance of raising awareness among healthcare providers and overcoming barriers to access for newer treatment options in order to reduce inequalities. [Extracted from the article]

Aim: To assess if early change in albuminuria was linked to an initial change in estimated glomerular filtration rate (eGFR) and long‐term kidney outcomes in people with type 2 diabetes (T2D) receiving sodium‐glucose cotransporter‐2 (SGLT2) inhibitors. Methods: Using a medical database from a multicentre healthcare institute in Taiwan, we retrospectively enrolled 8310 people receiving SGLT2 inhibitors from 1 June 2016 to 31 December 2021. We compared the risks of initial eGFR decline, major adverse renal events (MARE; >50% eGFR reduction or development of end‐stage kidney disease), major adverse cardiovascular events (MACE), or hospitalization for heart failure (HHF) using a Cox proportional hazards model. Results: In all, 36.8% (n = 3062) experienced a >30% decrease, 21.0% (n = 1743) experienced a 0%–30% decrease, 14.4% (n = 1199) experienced a 0%–30% increase, and 27.7% (n = 2306) experienced a >30% increase in urine albumin‐to‐creatine ratio (UACR) after 3 months of SGLT2 inhibitor treatment. Greater acute eGFR decline at 3 months correlated with greater UACR reduction: −3.6 ± 10.9, −2.0 ± 9.5, −1.1 ± 8.6, and −0.3 ± 9.7 mL/min/1.73 m2 for the respective UACR change groups (p < 0.001). Over a median of 29.0 months, >30% UACR decline was associated with a higher risk of >30% initial eGFR decline (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.61–4.47]), a lower risk of MARE (HR 0.66, 95% CI 0.48–0.89), and a comparable risk of MACE or HHF after multivariate adjustment (p < 0.05). The nonlinear analysis showed early UACR decline was linked to a lower risk of MARE but a higher risk of initial steep eGFR decline of >30%. Conclusion: Physicians should be vigilant for the potential adverse effects of abrupt eGFR dipping associated with a profound reduction in UACR, despite the favourable long‐term kidney outcomes in the population with T2D receiving SGLT2 inhibitor treatment. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add‐on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). Materials and Methods: This multicentre, randomized, 104‐week, open‐label trial randomized 105 patients with drug‐naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104. Results: HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was −2.56% in the TCT group vs. –2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P =.027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P <.001). TCT was well‐tolerated and had fewer adverse events than SAT. Conclusions: Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients. [ABSTRACT FROM AUTHOR]

Aim: To explore the effect of canagliflozin on kidney and cardiovascular events and safety outcomes in individuals with type 2 diabetes and chronic kidney disease across geographic regions and racial groups. Materials and Methods: A stratified Cox proportional hazards model was used to assess efficacy and safety outcomes by geographic region and racial group. The primary composite outcome was a composite of end‐stage kidney disease (ESKD), doubling of the serum creatinine (SCr) level, or death from kidney or cardiovascular causes. Secondary outcomes included: (i) cardiovascular death or heart failure (HF) hospitalization; (ii) cardiovascular death, myocardial infarction (MI) or stroke; (iii) HF hospitalization; (iv) doubling of the SCr level, ESKD or kidney death; (v) cardiovascular death; (vi) all‐cause death; and (vii) cardiovascular death, MI, stroke, or hospitalization for HF or for unstable angina. Results: The 4401 patients were divided into six geographic region subgroups: North America (n = 1182, 27%), Central and South America (n = 941, 21%), Eastern Europe (n = 947, 21%), Western Europe (n = 421, 10%), Asia (n = 749, 17%) and Other (n = 161, 4%). The analyses included four racial groups: White (n = 2931, 67%), Black or African American (n = 224, 5%), Asian (n = 877, 20%) and Other (n = 369, 8%). Canagliflozin reduced the relative risk of the primary composite outcome in the overall trial by 30% (hazard ratio 0.70, 95% confidence interval 0.59‐0.82; P = 0.00001). Across geographic regions and racial groups, canagliflozin consistently reduced the primary composite endpoint without evidence of heterogeneity (interaction P values of 0.39 and 0.91, respectively) or significant safety outcome differences. Conclusions: Canagliflozin reduces the risk of kidney and cardiovascular events similarly across geographic regions and racial groups. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We conducted a 5 year post‐trial monitoring study of our previous randomized 24 week, open‐label, active‐controlled trial that showed beneficial effects of ipragliflozin on metabolic dysfunction‐associated steatotic liver disease (MASLD), identical to those of pioglitazone. Materials and Methods: In our previous trial, 66 patients with MASLD and type 2 diabetes were randomly assigned to receive either ipragliflozin (n = 32) or pioglitazone (n = 34). Upon its conclusion, 61 patients were monitored for 5 years for outcome measures of MASLD, glycemic, and metabolic parameters. Differences between the two groups were analyzed at baseline, 24 weeks, and 5 years; changes in outcome measures from baseline were also evaluated. Results: At 5 years, the mean liver‐to‐spleen attenuation ratio increased by 0.20 (from 0.78 ± 0.24 to 0.98 ± 0.20) in the ipragliflozin group and by 0.26 (from 0.76 ± 0.26 to 1.02 ± 0.20) in the pioglitazone group (P = 0.363). Similarly, ipragliflozin and pioglitazone significantly improved serum aminotransferase, HbA1c, and fasting plasma glucose levels over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat area observed at 24 weeks were sustained throughout the 5 years (−4.0%, P = 0.0075 and −7.6%, P = 0.045, respectively). Moreover, ipragliflozin significantly reduced the values of fibrosis markers (serum ferritin and FIB‐4 index), was well tolerated, and had a higher continuation rate for 5 years compared with pioglitazone. Conclusions: Ipragliflozin and pioglitazone improved MASLD and glycemic parameters over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat mass persisted for 5 years. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment‐refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single‐arm trial (EMPIRE‐01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE‐02) that followed on from EMPIRE‐01. Materials and Methods: The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE‐01 trial participated in EMPIRE‐02. Results: Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE‐02. The improvement in mean values of glycemic parameters observed in EMPIRE‐01 was not sustained in EMPIRE‐02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE‐02 after exclusion of this subject from analysis. Conclusions: Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option. [ABSTRACT FROM AUTHOR]

Purpose: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in managing cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) is evolving. This meta-analysis seeks to explore the influence of SGLT2i on the recurrence of atrial fibrillation (AF) following catheter ablation (CA) in individuals with T2DM qualitatively and quantitatively. Methods: A comprehensive literature search was conducted in electronic databases. Studies meeting predefined criteria were included. Individual patient data (IPD) were used from reconstructed time-to-event data to estimate hazard ratios (HRs) and 95% confidence intervals for AF recurrence. IPD meta-analysis was followed by a direct meta-analysis to assess the risk of AF recurrence. Results: A total of five studies [one randomized controlled trial (RCT) and four cohort studies] were included in this study, and five studies were included in the qualitative analysis, while four studies comprising 1043 patients with T2DM were included in the quantitative analysis. The pooled Kaplan–Meier curve based on reconstructed data showed a significantly lower risk of AF recurrence in the SGLT2i group compared with all antidiabetic drugs (log-rank P = 0.00011) and dipeptidyl-peptidase IV inhibitors (DPP4i) (log-rank P = 0.01). Cox regression analysis showed consistent results. Direct meta-analysis showed that SGLT2i, compared with all antidiabetic medications (HR 0.57, 95% CI [0.44, 0.73], I2) and DPP4i (HR 0.41, 95% CI [0.24, 0.70], I2), was associated with a lower risk of AF recurrence. Conclusions: SGLT2i are associated with a reduced risk of AF recurrence after CA in patients with T2DM. These results suggest that SGLT2i is promising in improving clinical outcomes for this population. [ABSTRACT FROM AUTHOR]

The article argues for elevating the standards in cardiovascular secondary prevention, with reference to a study which explored the association of treatment with sodium-glucose cotransporter-2 inhibitors and reduced risk of atrial fibrillation occurrence after catheter ablation in patients with type 2 diabetes mellitus.

Introduction: The 2021 European Society of Cardiology (ESC) Guidelines recommend the use of four different classes of drugs for heart failure with reduced ejection fraction (HFrEF): beta blockers (BB), sodium-glucose cotransporter-2 inhibitors (SGLT2i), angiotensin receptor/neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRAs). Moreover, the 2023 ESC updated Guidelines suggest an intensive strategy of initiation and rapid up-titration of evidence-based treatment before discharge, based on trials not using the four-pillars. We hypothesized that an early concomitantly administration and up-titration of four-pillars, compared with a conventional stepwise approach, may impact the vulnerable phase after hospitalization owing to HF. Methods: This prospective, single center, observational study included consecutive in-hospital patients with HFrEF. After performing propensity score matching, they were divided according to treatment strategy into group 1 (G1), with predischarge start of all four-pillars, with their up-titration within 1 month, and group 2 (G2) with the pre Guidelines update stepwise four-pillars introduction. HF hospitalization, cardiovascular (CV) death, and the composite of both were evaluated between the two groups at 6-month follow-up. Results: The study included a total of 278 patients who completed 6-month follow-up (139 for both groups). There were no differences in terms of baseline features between the two groups. At survival analysis, HF hospitalization risk was significantly lower in G1 compared with G2 (p < 0.001), while no significant differences were observed regarding CV death (p = 0.642) or the composite of CV death and HF hospitalization (p = 0.135). Conclusions: In our real-world population, patients with HF treated with a predischarge and simultaneous use of four-pillars showed a reduced risk of HF hospitalization during the vulnerable phase after discharge, compared with a conventional stepwise approach. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the effects of sodium-glucose co-transporter inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase-4 inhibitors (DPP4i) on individuals subjected to diabetes and COVID-19. Methods: PubMed, Embase, Web of Science, and Cochrane Library were systematically searched to cover studies (except for case reports and review studies) published until August 30, 2022. The primary outcome was the mortality of people with diabetes and COVID-19. The secondary outcomes comprised the requiring intensive care unit (ICU) admission and mechanical ventilation. Two reviewers independently screened studies, abstracted data, and assessed risk-of-bias. Furthermore, the network meta-analyses (NMA) were conducted. Results: A total of 12 trials were involved in the analysis. The OR and 95% CI of mortality for SGLT2i compared with SGLT2i + GLP-1RA and DPP4i reached 0.41 (0.17,0.97) and 0.69 (0.49,0.98), respectively. The OR and 95% CI of requiring mechanical ventilation for SGLT2i compared with the DPP4i reached 0.85 (0.75,0.97). Conclusions: As revealed by the result of this study, SGLT2i is associated with the lower mortality rate in people with diabetes and COVID-19 among novel glucose-lowering drugs. And SGLT2i is linked to lower requiring mechanical ventilation. These findings can have a large impact on clinicians' decisions amid the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to investigate the impact of the sodium–glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET). RESEARCH DESIGN AND METHODS: In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R , S)-[18F]fluoro-6-thia-heptadecanoic acid. Treatment effects were assessed using ANCOVA, and the results are reported as least square means and 95% CIs for the difference between groups. RESULTS: A total of 38 patients (dapagliflozin n = 21; placebo n = 17) completed the study. After 6 weeks, skeletal muscle FA uptake was increased by dapagliflozin compared with placebo (1.0 [0.07, 2.0] μmol ⋅ 100 g−1 ⋅ min−1; P = 0.032), whereas uptake was not significantly changed in the small intestine or visceral or subcutaneous adipose tissue. Dapagliflozin treatment significantly increased whole-brain FA uptake (0.10 [0.02, 0.17] μmol ⋅ 100 g−1 ⋅ min−1; P = 0.01), an effect observed in both gray and white matter regions. CONCLUSIONS: Six weeks of treatment with dapagliflozin increases skeletal muscle and brain FA uptake, partly driven by a rise in free FA availability. This finding is in accordance with previous indirect measurements showing enhanced FA metabolism in response to SGLT2 inhibition and extends the notion of a shift toward increased FA use to muscle and brain. [ABSTRACT FROM AUTHOR]

Volume overload represents a hallmark clinical feature linked to the development and progression of heart failure (HF). Alleviating signs and symptoms of volume overload represents a foundational HF treatment target that is achieved using loop diuretics in the acute and chronic setting. Recent work has provided evidence to support guideline-directed medical therapies, such as sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor (MR) antagonists, as important adjunct diuretics that may act synergistically when used with background loop diuretics in people with chronic HF. Furthermore, there is growing interest in understanding the role of SGLT2 inhibitors, carbonic anhydrase inhibitors, thiazide diuretics, and MR antagonists in treating volume overload in patients hospitalized for acute HF, particularly in the setting of loop diuretic resistance. Thus, the current review demonstrates that: (i) SGLT2 inhibitors and MR antagonists confer long-term cardioprotection in chronic HF patients but it is unclear whether natriuresis or diuresis represents the primary mechanisms for this benefit, (ii) SGLT2 inhibitors, carbonic anhydrase inhibitors, and thiazide diuretics increase natriuresis in the acute HF setting, but implications on long-term outcomes remain unclear and warrants further investigation, and (iii) a multi-nephron segment approach, using agents that act on distinct segments of the nephron, potentiate diuresis to alleviate signs and symptoms of volume overload in acute HF. [ABSTRACT FROM AUTHOR]

Introduction Mechanisms underlying kidney benefits with sodium-glucose cotransporter-2 (SGLT2) inhibition in heart failure and/or type 2 diabetes (T2D) with established cardiovascular disease are currently unclear. Methods We evaluated post hoc the factors mediating the effect of empagliflozin on a composite kidney outcome (first sustained estimated glomerular filtration rate ≥40% reduction from baseline, initiation of renal replacement therapy or death due to kidney disease) in EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients). Variables, calculated as change from baseline or updated mean, were evaluated as time-dependent covariates and using a landmark approach (at Week 12) in Cox regression analyses. In multivariable analyses, variables with the greatest mediating effect were added using a step-up procedure. Results In univariable time-dependent updated mean covariate analyses, the strongest mediator was hematocrit (99.5% mediation). Hemoglobin, uric acid and urine albumin-to-creatinine ratio mediated 79.4%, 33.2% and 31.0%, respectively. Multivariable analyses were not performed due to the very strong mediation effect of hematocrit. In univariable Week 12 landmark change from baseline analyses, the strongest mediators included hematocrit (40.7%), glycated hemoglobin (28.3%), systolic blood pressure (16.8%) and free fatty acids (16.5%), which yielded a combined mediation of 78.9% in multivariable analysis. Conclusions Changes in hematocrit and hemoglobin were the strongest mediators of empagliflozin's kidney benefits in EMPA-REG OUTCOME participants with T2D and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Limited direct comparative studies exist in terms of the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase-4 inhibitors (DPP4is) on the kidney outcomes in Japanese individuals with type 2 diabetes. Methods: This retrospective cohort study included 561 Japanese adults with type 2 diabetes, who were newly prescribed either an SGLT2i or a DPP4i and had an eGFR ≥ 30 mL/min/1.73 m2. The cohort comprised 207 women and 354 men, with a mean (± standard deviation) age of 63 (± 12) years. The exposure and outcome were SGLT2i or DPP4i initiation and eGFR slope during the overall follow-up period, restricted to participants who were followed for ≥2 years. We adopted the on-treatment analysis. Analysis of covariance was used to compare the adjusted eGFR slope between the two groups, incorporating 10 variables at baseline. Results: During the median follow-up period of 3.4 years, least square mean (95% CI) eGFR slopes were −1.91 (−2.15, −1.67) and −1.12 (−1.58, −0.67) mL/min/1.73 m2/year in individuals treated with a DPP4i (n = 460) and an SGLT2i (n = 101), respectively, demonstrating statistical significance (p = 0.002). The robustness of this finding was strengthened by sensitivity analyses. Conclusions: This study provides potential evidence of the superiority of SGLT2is over DPP4is in slowing kidney function decline in Japanese adults with type 2 diabetes and eGFR ≥ 30 mL/min/1.73 m2. [ABSTRACT FROM AUTHOR]

The article discusses the ARISE-HF trial, which aimed to evaluate the safety and efficacy of a novel aldose reductase inhibitor (AT-001) in patients with diabetic cardiomyopathy (DbCM) and stage B heart failure (HF). DbCM is a complication of type 2 diabetes mellitus (T2DM) that can lead to structural and functional abnormalities in the heart. The study found that AT-001 did not significantly improve exercise capacity compared to placebo, but there was a potential benefit in patients not receiving other cardioprotective drugs. However, further research is needed to confirm these findings and determine the clinical role of AT-001 in combination with other therapies. [Extracted from the article]

Cancer frequently develops resistance to the majority of chemotherapy treatments. This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors, specifically Canagliflozin (CAN), Dapagliflozin (DAP), Empagliflozin (EMP), and Doxorubicin (DOX), using in vitro experimentation. The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin (DOX) in MCF-7 cells. Interestingly, it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth. Notably, when these medications were combined with DOX, there was a considerable inhibition of glucose consumption, as well as reductions in intracellular ATP and lactate levels. Moreover, this effect was found to be dependent on the dosages of the drugs. In addition to effectively inhibiting the cell cycle, the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression. This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications, namely CAN, DAP, and EMP, on the responsiveness to the anticancer properties of DOX. The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2. [ABSTRACT FROM AUTHOR]

Objective: To describe the pharmacology, clinical efficacy, and safety evidence of sotagliflozin, the first approved dual inhibitor of sodium-glucose cotransporter (SGLT) 1 and SGLT2, in heart failure (HF) management. Data sources: A literature search of studies published between January 2012 and September 2023 were identified using PubMed, MEDLINE, and clinicaltrials.gov with search terms of "sotagliflozin," "Inpefa," or "LX4211." Study selection and data extraction: All available studies in English were considered. Studies were included if they investigated drug pharmacology, efficacy, or safety information. Data synthesis: Two phase 3 trials of sotagliflozin, SOLOIST-WHF and SCORED, evaluated sotagliflozin compared with placebo in patients with type 2 diabetes mellitus (T2DM). SOLOIST-WHF reported a statistically decreased rate of cardiovascular and HF events with sotagliflozin (hazard ratio [HR] = 0.67, 95% CI = 0.52-0.85), while SCORED found a statistically significant decrease in incidence of cardiovascular events in patients with T2DM, chronic kidney disease (CKD), and risk factors for cardiovascular disease in patients in the sotagliflozin group (HR = 0.74, 95% CI = 0.63-0.88). Relevance to patient care and clinical practice in comparison to existing agents: While approval of sotagliflozin expands treatment options for patients with HF, the SGLT2 inhibitors, dapagliflozin and empagliflozin, have more data supporting their use in HF, additional risk reduction benefits in patients with CKD, and approval for use in T2DM. Landmark trials of sotagliflozin required a previous diagnosis of T2DM, despite the broader approved indication. Where sotagliflozin will be adopted into the treatment of HF is unclear due to the evidence and benefits of already established SGLT2 inhibitors and the need for comparison with SGLT2 inhibitors. Conclusion: Given the limitations of currently available evidence, including difficulty in fully interpreting the trial results due to changes in primary endpoints, not adjudicating the events, and not reaching the original power calculations, more investigation is warranted to determine the benefit of sotagliflozin compared with SGLT2 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Heart failure with preserved ejection fraction (HFpEF) is common in type 2 diabetes mellitus (T2D), leading to high morbidity and mortality. Managing HFpEF in diabetic patients is challenging with limited treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown potential cardiovascular benefits. This meta-analysis compares the effects of GLP1-RA and SGLT2 inhibitors on HFpEF in T2D patients. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating GLP1-RA and SGLT2 inhibitors' impact on HFpEF in T2D patients. Databases searched included PubMed, MEDLINE, and Cochrane Library up to July 2024. Primary outcomes were changes in left ventricular ejection fraction (LVEF), myocardial fibrosis (extracellular volume fraction, ECV), and functional capacity (6-minute walk test, 6MWT). Secondary outcomes included HbA1c, body weight, and systolic blood pressure (SBP). Results: Twelve studies with 3,428 patients (GLP1-RA: 1,654; SGLT2 inhibitors: 1,774) were included. Both GLP1-RA and SGLT2 inhibitors significantly improved LVEF compared to placebo (GLP1-RA: mean difference [MD] 2.8%, 95% confidence interval [CI] 1.5 to 4.1, p < 0.001; SGLT2 inhibitors: MD 3.2%, 95% CI 2.0 to 4.4, p < 0.001). SGLT2 inhibitors significantly reduced myocardial fibrosis (MD -3.5%, 95% CI -4.2 to -2.8, p < 0.001) more than GLP1-RA (MD -2.3%, 95% CI -3.0 to -1.6, p < 0.001). Functional capacity improved significantly with both treatments (GLP1-RA: MD 45 m, 95% CI 30 to 60, p < 0.001; SGLT2 inhibitors: MD 50 m, 95% CI 35 to 65, p < 0.001). Secondary outcomes showed reductions in HbA1c (GLP1-RA: MD -1.1%, 95% CI -1.4 to -0.8, p < 0.001; SGLT2 inhibitors: MD -1.0%, 95% CI -1.3 to -0.7, p < 0.001) and body weight (GLP1-RA: MD -2.5 kg, 95% CI -3.1 to -1.9, p < 0.001; SGLT2 inhibitors: MD -2.0 kg, 95% CI -2.6 to -1.4, p < 0.001). Both treatments significantly lowered SBP (GLP1-RA: MD -5.2 mmHg, 95% CI -6.5 to -3.9, p < 0.001; SGLT2 inhibitors: MD -4.8 mmHg, 95% CI -6.0 to -3.6, p < 0.001). Conclusions: GLP1-RA and SGLT2 inhibitors significantly benefit HFpEF management in T2D patients. SGLT2 inhibitors reduce myocardial fibrosis more effectively, while both improve LVEF, functional capacity, and metabolic parameters. These therapies should be integral to HFpEF management in diabetic patients. Further research is needed on long-term outcomes and potential combined therapy effects. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated reduction in heart failure outcomes in patients with type 2 diabetes mellitus, although the exact mechanism of benefit remains unclear. Alteration in left atrial (LA) function due to chronic pressure or volume overload is a hallmark of heart failure. Objective: To evaluate the effect of the SGLT2 inhibitor empagliflozin on LA volume and function. Methods: 90 patients with coronary artery disease and type 2 diabetes (T2DM) were randomized to empagliflozin (n = 44) or placebo (n = 46), and underwent cardiac magnetic resonance (CMR) imaging at baseline and after 6 months. The main outcome was change in LA volume; LA function, including active and passive components, was also measured by a blinded reader. Results: At baseline, there was no significant difference in LA volumes between the empagliflozin (indexed maximum LA volume 26.4 ± 8.4mL/m2, minimum LA volume 11.1 ± 5.7mL/m2) and placebo (indexed maximum LA volume 28.7 ± 8.2mL/m2, minimum LA volume 12.6 ± 5.0mL/m2) groups. After 6 months, changes in LA volumes did not differ with adjusted difference (empagliflozin minus placebo): 0.99 mL/m2 (95% CI: -1.7 to 3.7 mL/m2; p = 0.47) for indexed maximum LA volume, and 0.87 mL/m2 (95% CI: -0.9 to 2.6 mL/m2; p = 0.32) for indexed minimum LA volume. Changes in total LA emptying fraction were also similar, with between-group adjusted mean difference − 0.01 (95% CI: -0.05 to 0.03, p = 0.59). Conclusion: SGLT2 inhibition with empagliflozin for 6 months did not have a significant impact on LA volume and function in patients with T2DM and coronary artery disease. (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes [EMPA-HEART]; NCT02998970). [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce heart failure (HF) hospitalizations, recurrent cardiovascular events, and chronic kidney disease (CKD) progression, and thus constitute a Class 1a recommendation in people with diabetes and atherosclerotic cardiovascular disease, HF, or CKD and in people with severe albuminuria or HF, regardless of diabetes status. The purpose of this study was to comprehensibly characterize the rate of SGLT2 inhibitor prescriptions among people with a Class 1a recommendation for SGLT2 inhibitor use. Among 3,189,827 adults from 28 U.S. health systems within Optum Labs Data Warehouse between April 1, 2022, and March 31, 2023, we assessed SGLT2 inhibitor prescription rates, stratified by presence of diabetes and Class 1a recommendation. Among 716,387 adults with diabetes, 63.4% had a Class 1a recommendation for SGLT2 inhibitor therapy. There was little difference by Class 1a recommendation status (present: 11.9%; 95% CI: 11.9%-12.0% vs absent: 11.4%; 95% CI: 11.3%-11.6%; standardized mean difference: 1.3%). Among 2,473,440 adults without diabetes, 6.2% had a Class 1a recommendation for SGLT2 inhibitor therapy, and 3.1% (3.0%-3.2%) of those received a prescription. Internists/family practitioners initiated SGLT2 inhibitor prescriptions most commonly among people with diabetes, whereas specialists initiated SGLT2 inhibitor prescriptions most commonly among people without diabetes. No health system had >25% SGLT2 inhibitor prescription rate among people with a Class 1a recommendation. Health systems with higher proportions of patients with commercial insurance and lower proportions with Medicare had higher SGLT2 inhibitor prescription rates. In this analysis of U.S. data from 2022 to 2023, SGLT2 inhibitor prescription among people with a Class 1a recommendation is low. Interventions are needed to increase uptake of guideline-recommended SGLT2 inhibitor use. [ABSTRACT FROM AUTHOR]

Emerging data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve kidney outcomes for people with type 2 diabetes (T2D). Direct comparisons of the kidney and cardiovascular effectiveness of GLP-1 RA with sodium-glucose cotransporter 2 inhibitors (SGLT2i), a first-line therapy for this population, are needed. The authors compared kidney and cardiovascular outcomes for new users of SGLT2i and GLP-1 RAs with T2D. Using propensity score overlap weighting, we analyzed electronic health record data from 20 U.S. health systems contributing to PCORnet between 2015 and 2020. The primary kidney outcome was a composite of sustained 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease, or all-cause mortality over 2 years or until censoring. In addition, we examined cardiovascular and safety outcomes. The weighted study cohort included 35,004 SGLT2i and 47,268 GLP-1 RA initiators. Over a median of 1.2 years, the primary outcome did not differ between treatments (HR: 0.91; 95% CI: 0.81-1.02), although SGLT2i were associated with a lower risk of 40% eGFR decline (HR: 0.77; 95% CI: 0.65-0.91). Risks of mortality (HR: 1.08; 95% CI: 0.92-1.27), a composite of stroke, myocardial infarction, or death (HR: 1.03; 95% CI: 0.93-1.14), and heart failure hospitalization (HR: 0.95; 95% CI: 0.80-1.13) did not differ. Genital mycotic infections were more common for SGLT2i initiators, but other safety outcomes did not differ. The results were similar regardless of chronic kidney disease status. SGLT2i and GLP-1 RAs led to similar kidney and cardiovascular outcomes in people with T2D, though SGLT2i initiation was associated with a lower risk of 40% eGFR decline. (Evaluating Comparative Effectiveness of Empagliflozin in Type 2 Diabetes Population With and Without Chronic Kidney Disease; NCT05465317) [ABSTRACT FROM AUTHOR]

Background: In this nationwide register study, we examined the initiation of a second-line antidiabetic medicine (ADM) among new patients receiving regular metformin monotherapy in Finland during 2011–2022. We also reflected the second-line treatment patterns on changes in the reimbursement policy, and the national type 2 diabetes (T2D) care guidelines. Methods: Using register data on all reimbursed ADM purchases during 2010–2022, we defined nine annual cohorts of patients initiating regular metformin monotherapy during 2011–2019, each with a three-year follow-up. Descriptive methods were used to study the patterns of metformin monotherapy and second-line intensification over time. Proportional hazards models were used to analyse the take-up of the second-line ADM. Results: The share of new patients initiating metformin use (11–13% of all metformin users) and regular metformin use (83–85% of all new metformin users) remained stable. In all cohorts, 16–19% of the patients took up a second-line ADM (median time to intensification 1.5 years). With the 2011 cohort as reference, the highest proportion of new regular metformin users taking up a second ADM (hazard ratio 1.12. 95% confidence interval 1.07 ; 1.16, P <.0001) was in the 2019 cohort. In the 2017 cohort, the proportion of patients initiating sodium-glucose cotransporter 2 inhibitors as second-line treatment surpassed those initiating dipeptidyl peptidase-4 inhibitors. The reimbursement policy restricted the use of GLP-1-analogues. Conclusions: Second-line treatment intensification patterns over time paralleled the changes in the reimbursement system. Thus, our findings suggest that the reimbursement policy may influence the use of ADMs in Finland. [ABSTRACT FROM AUTHOR]

Background: The relationship between sodium-glucose cotransporter 2 (SGLT2) inhibitors and prostate cancer is still unknown. Although these inhibitors can influence tumor glycolysis, the underlying mechanism requires further exploration. Methods: A two-sample two-step MR was used to determine 1) causal effects of SGLT2 inhibition on prostate cancer; 2) causal effects of 1,400 circulating metabolites or metabolite ratios on prostate cancer; and 3) mediation effects of these circulating metabolites. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene and glycated hemoglobin level (HbA1c). Additionally, positive control analysis on type 2 diabetes mellitus (T2DM) was conducted to test the selection of genetic proxies. Phenome Wide Association Study (PheWAS) and MR-PheWAS analysis were used to explore potential treatable diseases and adverse outcomes of SGLT2 inhibitors. Results: Genetically predicted SGLT2 inhibition (per 1 SD decrement in HbA1c) was associated with reduced risk of T2DM [odds ratio (OR) = 0.66 (95% CI 0.53, 0.82), P = 1.57 × 10-4]; prostate cancer [0.34 (0.23, 0.49), P = 2.21 × 10-8] and prostate-specific antigen [0.26 (0.08, 0.81), P = 2.07 × 10-2]. The effect of SGLT2 inhibition on prostate cancer was mediated by uridine level, with a mediated proportion of 9.34% of the total effect. In MR-PheWAS, 65 traits were found to be associated with SLGT2 inhibitors (P < 1.78 × 10-5), and among them, 13 were related to diabetes. Conclusion: Our study suggested that SGLT2 inhibition could lower prostate cancer risk through uridine mediation. More mechanistic and clinical research is necessary to explore how uridine mediates the link between SGLT2 inhibition and prostate cancer. [ABSTRACT FROM AUTHOR]

Background/Objectives: The health burden of metabolic dysfunction-associated fatty liver disease (MASLD) has been increasing lately. Cardiovascular disease (CVD) is the main cause of death in MASLD patients; therefore, the treatments for MASLD should improve both CV risk factors such as obesity, diabetes, and dyslipidemia, in addition to an improvement in liver function. The evidence on the long-term effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on the progression of MASLD in Asian populations is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at our institute. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between 1 April 2014 and 31 March 2018. We collected the data on metabolic parameters, including laboratory data and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. Three-year SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein cholesterol, triglyceride, and non-high-density lipoprotein cholesterol (non-HDL-C). Such favorable changes in serum lipids were remarkable in patients with statins. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, long-term SGLT2is treatment may be an ideal therapy for MASLD patients. [ABSTRACT FROM AUTHOR]

Background Pre–diabetes mellitus (DM) is associated with proteinuria, a risk factor for chronic kidney disease. While people with human immunodeficiency virus (HIV; PWH) have a higher risk of proteinuria than people without HIV (PWOH), it is unknown whether incident proteinuria differs by HIV serostatus among prediabetic persons. Methods The urine protein-to-creatinine ratio was measured at semiannual visits among men in the Multicenter AIDS Cohort Study since April 2006. Men with pre-DM on or after April 2006 and no prevalent proteinuria or use of antidiabetic medications were included. Pre-DM was defined as a fasting glucose level of 100–125 mg/dL confirmed within a year by a repeated fasting glucose or hemoglobin A1c measurement of 5.7%–6.4%. Incident proteinuria was defined as a urine protein-to-creatinine ratio (UPCR) >200 mg/g, confirmed within a year. We used Poisson regression models to determine whether incident proteinuria in participants with pre-DM differed by HIV serostatus and, among PWH, whether HIV-specific factors were related to incident proteinuria. Results Between 2006 and 2019, among 1276 men with pre-DM, proteinuria developed in 128 of 613 PWH (21%) and 50 of 663 PWOH (8%) over a median 10-year follow-up. After multivariable adjustment, the incidence of proteinuria in PWH with pre-DM was 3.3 times (95% confidence interval, 2.3–4.8 times) greater than in PWOH (P <.01). Among PWH, current CD4 cell count <50/µL (P <.01) and current use of protease inhibitors (P =.03) were associated with incident proteinuria, while lamivudine and integrase inhibitor use were associated with a lower risk. Conclusions Among men with pre-DM, the risk of incident proteinuria was 3 times higher in PWH. Strategies to preserve renal function are needed in this population. [ABSTRACT FROM AUTHOR]

This article explores the use of mechanical circulatory supports (MCS), specifically left ventricular assist devices (LVADs), in the treatment of advanced heart failure. It highlights the high mortality rates associated with heart failure, particularly among younger individuals, and the increasing incidence of cardiogenic shock. The article discusses the variation in LVAD implantation rates across European countries and the impact of the COVID-19 pandemic on implantation activity. It also addresses factors that may contribute to the lack of global implementation of LVADs, including concerns about the percutaneous power cable and the risk of infection. The article suggests that improving the network structure, educating practitioners, and redefining the role of LVADs in accessing transplantation are necessary to reduce mortality among young heart failure patients. [Extracted from the article]

Aim Materials and Methods Results Conclusions This nationwide cohort study evaluated the impact of sodium–glucose co‐transporter‐2 inhibitors (SGLT2i) on patients with type 2 diabetes mellitus (T2DM) after ischaemic stroke (IS), aiming to compare clinical outcomes between SGLT2i‐treated patients and those not receiving SGLT2i.Utilizing Taiwan's National Health Insurance Research Database, we identified 707 patients with T2DM treated with SGLT2i and 27 514 patients not treated with SGLT2i after an IS, respectively, from 1 May 2016 to 31 December 2019. Propensity score matching was applied to balance baseline characteristics. The follow‐up period extended from the index date (3 months after the index acute IS) until the independent occurrence of the study outcomes, 6 months after discontinuation of the index drug, or the end of the study period (31 December 2020), whichever came first.After propensity score matching, compared with the non‐SGLT2i group (n = 2813), the SGLT2i group (n = 707) exhibited significantly lower recurrent IS rates (3.605% per year vs. 5.897% per year; hazard ratio: 0.55; 95% confidence interval: 0.34–0.88; p = 0.0131) and a significant reduction in all‐cause mortality (5.396% per year vs. 7.489% per year; hazard ratio: 0.58; 95% confidence interval: 0.39–0.85; p = 0.0058). No significant differences were observed in the rates of acute myocardial infarction, cardiovascular death, heart failure hospitalization, or lower limb amputation.Our findings indicate significantly lower risks of recurrent IS and all‐cause mortality among patients with T2DM receiving SGLT2i treatment. Further studies are required to validate these results and investigate the underlying mechanisms behind the observed effects. [ABSTRACT FROM AUTHOR]

Introduction: There remains an unmet need to reduce kidney and cardiovascular risk in patients with chronic kidney disease (CKD). This report is therefore intended to provide real-world clinical guidance to primary care providers on sodium-glucose co-transporter-2 (SGLT2) inhibitor use in patients with CKD, focusing on practical considerations. Initially developed as glucose-lowering drugs, SGLT2 inhibitors preserve kidney function and reduce risks of cardiovascular events and mortality. Clinical benefits of SGLT2 inhibitors in CKD have been demonstrated in multiple clinical trials, yet utilization in practice remains relatively low, likely due to the complexity of labeled indications (past and present) and misconceptions about SGLT2 inhibitors as a class. Methods: A panel of 8 US-based nephrologists convened in August 2022 to develop consensus guidance for the primary care community surrounding risk assessment as well as initiation and implementation of SGLT2 inhibitors in patients with CKD. Here, we provide an adapted version of the Kidney Disease: Improving Global Outcomes (KDIGO) heatmap and a treatment-decision algorithm. Conclusions: We advocate SGLT2 inhibitors as co-first-line therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors, where RAAS inhibitor dose titration need not be completed before initiation of an SGLT2 inhibitor. In fact, SGLT2 inhibitor therapy may facilitate up-titration or maintenance of optimal RAAS inhibitor dosing. We describe potential strategies to aid implementation of an SGLT2 inhibitor in clinical practice, including improving education and awareness among care providers and patients and dispelling misconceptions about the safety of SGLT2 inhibitors. In summary, we support the use of SGLT2 inhibitors with RAAS inhibitors as co-first-line therapy in most patients with CKD. [ABSTRACT FROM AUTHOR]

Introduction: Data on sodium glucose co-transporter 2 inhibitors impact on lipids in patients with diabetes are available and only a handful of studies have explored this effect in individuals with both diabetes and renal impairment; lipid parameters were not the primary focus of those earlier studies. However, there is a significant research gap specifically addressing the influence of SGLT2 inhibitors on cholesterol fractions in patients exclusively with chronic kidney disease. This aim constitutes the central objective in this particular study. Methods: In this 3-month randomized controlled study, 30 patients with stage 3 chronic kidney disease and dyslipidemia were randomly assigned to receive either dapagliflozin 10 mg or placebo. Lipid profiles, renal function, and urinary albumin levels were assessed at baseline and after 3 months. Results: Compared to baseline, patients receiving dapagliflozin for 3 months showed significant improvements in serum creatinine (p <.001) and eGFR (p =.001). Total cholesterol and LDL-C levels decreased significantly (p =.010 and.006, respectively). While albumin-creatinine ratio also decreased, this change was not statistically significant. Additionally, HDL-C and TG not significantly increased. The control group without intervention experienced deterioration in serum creatinine and eGFR (p =.008, and.011, respectively), but no statistically significant lipid changes were observed. Furthermore, post-intervention total cholesterol moderately correlated with BMI (p =.032, R =.554), yet no predictors significantly influenced lipid levels in the multiple linear regression analysis. Conclusions: Dapagliflozin has a favorable effect on cholesterol fractions in stage 3 CKD patients without diabetes mellitus and this effect was different from that observed in patients with diabetes alone. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) are important second-line treatments for patients with type 2 diabetes mellitus (T2DM). Patients taking SGLT2i have favorable cardiovascular outcomes via various mechanisms, including autonomic nervous system (ANS) modulation. This study aimed to use neuroelectrocardiography (neuECG) to test the effects of SGLT2i or DPP4i on the ANS. Methods: Patients with T2DM, who did not reach target hemoglobin (Hb)A1C levels despite metformin treatment, were enrolled. SGLT2i or DPP4i were prescribed randomly unless a compelling indication was present. NeuECG and heart rate were recorded for 10 min before and after a 3-month treatment. The patients were treated according to standard practice and the obtained data for skin sympathetic nerve activity (SKNA) and ANS entropy were analyzed offline. Results: We enrolled 96 patients, of which 49 received SGLT2i and 47 received DPP4i. The baseline parameters were similar between the groups. No adverse event was seen during the study period. In the burst analysis of SKNA at baseline, all parameters were similar. After the 3-month treatment, the firing frequency was higher in SGLT2i group (0.104 ± 0.045 vs 0.083 ± 0.033 burst/min, p < 0.05), with increased long firing duration (7.34 ± 3.66 vs 5.906 ± 2.921, p < 0.05) in 3-s aSKNA scale; the other parameters did not show any significant change. By symbolic entropy, the most complex patterns (Rank 3) were found to be significantly higher in SGLT2i-treated patients than in DDP4i-treated group (0.084 ± 0.028 vs 0.07 ± 0.024, p = 0.01) and the direction of change in Rank 3, after SGLT2i treatment, was opposite to that observed in the DDP4i group (0.012 ± 0.036 vs. -0.005 ± 0.037, p = 0.024). Our findings demonstrated the favorable autonomic modulation by SGLTi and the detrimental effects of DPP4i on ANS. Conclusion: We demonstrated the autonomic modulation by SGLTi and DPP4i using SKNA in patients with DM, which might provide insights into the favorable outcomes of SGLT2i. Furthermore, we refined the analytical methods of neuECG, which uses SKNA to evaluate autonomic function. [ABSTRACT FROM AUTHOR]

The rising prevalence of diabetes mellitus has casted a spotlight on one of its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for diabetes management, are increasingly studied for their cognitive benefits. These benefits may include reduction of oxidative stress and neuroinflammation, decrease of amyloid burdens, enhancement of neuronal plasticity, and improved cerebral glucose utilization. The multifaceted effects and the relatively favorable side-effect profile of SGLT2 inhibitors render them a promising therapeutic candidate for cognitive disorders. Nonetheless, the application of SGLT2 inhibitors for cognitive impairment is not without its limitations, necessitating more comprehensive research to fully determine their therapeutic potential for cognitive treatment. In this review, we discuss the role of SGLT2 in neural function, elucidate the diabetes-cognition nexus, and synthesize current knowledge on the cognitive effects of SGLT2 inhibitors based on animal studies and clinical evidence. Research gaps are proposed to spur further investigation. [ABSTRACT FROM AUTHOR]

ABSTRACT Canagliflozin (CFZ) is a sodium‐glucose cotransporter‐2 inhibitor that has shown promising results as a drug for the treatment of insulin dysregulation in horses. Even though CFZ is used clinically, no pharmacokinetic data has previously been published. In this study, the pharmacokinetics of CFZ after administration of a single oral dose of 1.8 mg/kg in eight healthy Icelandic horses was examined. Additionally, the effect of treatment on glucose and insulin levels in response to a graded glucose infusion was investigated. Plasma samples for CFZ quantification were taken at 0, 0.33, 0.66, 1, 1.33, 1.66, 2, 2.33, 2.66, 3, 3.5, 4, 5, 6, 8, 12, 24, 32, and 48 h post administration. CFZ was quantified using UHPLC coupled to tandem quadrupole mass spectrometry (UHPLC‐MS/MS). A non‐compartmental analysis revealed key pharmacokinetic parameters, including a median Tmax of 7 h, a Cmax of 2350 ng/mL, and a t1/2Z of 28.5 h. CFZ treatment reduced glucose (AUCGLU, p = 0.001) and insulin (AUCINS, p = 0.04) response to a graded glucose infusion administered 5 h after treatment. This indicates a rapid onset of action following a single dose in healthy Icelandic horses. No obvious adverse effects related to the treatment were observed. [ABSTRACT FROM AUTHOR]

Background Cardiac surgery-associated acute kidney injury (CSA-AKI) is a serious complication in patients undergoing cardiac surgery with extracorporeal circulation (ECC) that increases postoperative complications and mortality. CSA-AKI develops due to a combination of patient- and surgery-related risk factors that enhance renal ischemia–reperfusion injury. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) such as empagliflozin reduce renal glucose reabsorption, improving tubulo-glomerular feedback, reducing inflammation and decreasing intraglomerular pressure. Preclinical studies have observed that SGLT2i may provide significant protection against renal ischemia–reperfusion injury due to their effects on inadequate mitochondrial function, reactive oxygen species activity or renal peritubular capillary congestion, all hallmarks of CSA-AKI. The VERTIGO (EValuating the Effect of periopeRaTIve empaGliflOzin) trial is a Phase 3, investigator-initiated, randomized, double-blind, placebo-controlled, multicenter study that aims to explore whether empagliflozin can reduce the incidence of adverse renal outcomes in cardiac surgery patients. Methods The VERTIGO study (EudraCT: 2021-004938-11) will enroll 608 patients that require elective cardiac surgery with ECC. Patients will be randomly assigned in a 1:1 ratio to receive either empagliflozin 10 mg orally daily or placebo. Study treatment will start 5 days before surgery and will continue during the first 7 days postoperatively. All participants will receive standard care according to local practice guidelines. The primary endpoint of the study will be the proportion of patients that develop major adverse kidney events during the first 90 days after surgery, defined as ≥25% renal function decline, renal replacement therapy initiation or death. Secondary, tertiary and safety endpoints will include rates of AKI during index hospitalization, postoperative complications and observed adverse events. Conclusions The VERTIGO trial will describe the efficacy and safety of empagliflozin in preventing CSA-AKI. Patient recruitment is expected to start in May 2024. [ABSTRACT FROM AUTHOR]

The article discusses the need for reliable biomarkers to detect pulmonary congestion in patients with heart failure (HF) in order to prevent hospitalizations and improve patient outcomes. The current biomarkers used in clinical practice, B-type natriuretic peptides (NPs), have limitations such as being affected by comorbidities and having inconsistent measurement intervals. The article presents the BioMEMS study, which aims to identify alternative biomarkers that accurately reflect worsening congestion and can be easily measured. The study collects blood samples from HF patients and analyzes them using the Olink Cardiovascular III panel to evaluate the relationship between biomarkers and pulmonary artery pressures. The ultimate goal is to develop a biomarker-based management strategy for HF patients that is decentralized, manageable, and economically sustainable. [Extracted from the article]

This article provides concise summaries of recent studies published in the European Journal of Heart Failure that are relevant to heart failure specialists. The studies cover various topics, including the importance of screening for malnutrition in patients with advanced heart failure, the role of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes and heart failure, the safety of diuretic use in pregnant women with structural heart disease, and the importance of optimal heart failure management after mitral transcatheter edge-to-edge repair. The findings highlight the poor prognosis for malnourished heart failure patients, the consistent benefits of sodium-glucose cotransporter 2 inhibitors in improving clinical outcomes, the safety of loop diuretic use during pregnancy, and the factors associated with heart failure hospitalization risk after mitral transcatheter edge-to-edge repair. [Extracted from the article]