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A post hoc analysis of the SUSTAIN 6 trial evaluated the effect of once-weekly semaglutide on cardiovascular (CV) outcomes in people with type 2 diabetes (T2D) stratified by the number of vascular territories with atherosclerosis at baseline. The study found that semaglutide was associated with a consistent reduction in CV events across all groups, including those with polyvascular disease. The absolute risk reduction for CV events was greater in people with polyvascular disease, suggesting that they may derive greater benefit from semaglutide treatment due to their higher CV risk. However, the study had limitations, and further research is needed to confirm these findings. [Extracted from the article]

4 Dave CV, Kim SC, Goldfine AB, Glynn RJ, Tong A, Patorno E. Risk of cardiovascular outcomes in patients with type 2 diabetes after addition of SGLT2 inhibitors versus sulfonylureas to baseline GLP-1RA therapy. Before matching, patients in the SGLT2 inhibitor group were younger, more likely to be on metformin/glucagon-like peptide-1 receptor agonists/insulin, and had lower rates of comorbid heart failure, microvascular disease, stroke and chronic kidney disease (Table S2). Keywords: cardiovascular disease; real-world evidence; SGLT2 inhibitor; sulphonylureas; type 2 diabetes EN cardiovascular disease real-world evidence SGLT2 inhibitor sulphonylureas type 2 diabetes 2402 2409 8 07/04/23 20230801 NES 230801 INTRODUCTION Sulphonylureas (SUs) are widely used in type 2 diabetes (T2D), particularly in resource-constrained regions. Lower risk of cardiovascular events and death associated with initiation of sodium-glucose cotransporter-2 inhibitors versus sulphonylureas: Analysis from the CVD-REAL 2 study. [Extracted from the article]

This study of real‐world data from the Maccabi database in Israel compared the risk of heart failure hospitalization (HHF) or death in patients with type 2 diabetes (T2D) initiating sodium‐glucose cotransporter‐2 (SGLT2) inhibitors versus other glucose‐lowering drugs (OGLDs) according to baseline left ventricular (LV) ejection fraction (EF). After propensity‐matching patients by baseline EF there were 10 614 episodes of treatment initiation; 57% had diabetes for >10 years, the mean glycated haemoglobin level was 66 mmol/mol (8.2%), ∼43% had cardiovascular disease, ∼7% had heart failure and ∼ 20% had chronic kidney disease. A total of 2876 patients (∼9%) had reduced EF (<50%). Over a mean follow‐up of 1.5 years there were 371 HHFs or deaths, 88 (23.7%) in patients with reduced EF. Initiation of SGLT2 inhibitors versus OGLDs was associated with lower risk of HHF or death overall (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.46‐0.70]; P < 0.001) and in patients with both reduced EF (HR 0.61, 95% CI 0.40‐0.93) and preserved EF (HR 0.55, 95% CI 0.43‐0.70), with no significant heterogeneity (Pinteraction = 0.72). Our findings from real‐world clinical practice show that the lower risk of HHF and death associated with use of SGLT2 inhibitors versus OGLDs is consistent in T2D patients with both reduced and preserved EF. [ABSTRACT FROM AUTHOR]

While randomized controlled trials (RCTs) are the gold standard for comparative effectiveness research, they are unable to provide the answers to all pertinent clinical and research questions. Real world evidence (RWE), that is, clinical evidence obtained outside RCTs and often through routine clinical practice, offers the potential to conduct observational studies that accelerate advances in care, improve outcomes for patients, and provide important insights that can answer important questions. Once appropriate information technology is available, real world data can be cost‐effective to generate. RWE serves a vital role in the evaluation of treatment strategies for which there are no RCTs and for describing patterns of care. RWE also serves as an important adjunct to RCTs and can be used to determine if benefits seen in RCTs extend to clinical practice, provide insight into the findings of RCTs, generate hypotheses for future RCTs, and inform the design of future RCTs. These potential benefits must be balanced against some of the important limitations of RWE, including variable data quality, lack of granularity for important clinical variables, and the potential for bias and confounding. By using appropriate analytic techniques and study design, these limitations can be minimized but not eliminated. Going forward, RWE studies may be enhanced by using rigorous data quality standards, incorporating randomization, developing more prospective registries, and better leveraging data from electronic health records. [ABSTRACT FROM AUTHOR]

The multinational, observational CVD‐REAL study recently showed that initiation of sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2i) was associated with significantly lower rates of death and heart failure vs other glucose‐lowering drugs (oGLDs). This sub‐analysis of the CVD‐REAL study sought to determine the association between initiation of SGLT‐2i vs oGLDs and rates of myocardial infarction (MI) and stroke. Medical records, claims and national registers from the USA, Sweden, Norway and Denmark were used to identify patients with T2D who newly initiated treatment with SGLT‐2i (canagliflozin, dapagliflozin or empagliflozin) or oGLDs. A non‐parsimonious propensity score was developed within each country to predict initiation of SGLT‐2i, and patients were matched 1:1 in the treatment groups. Pooled hazard ratios (HRs) and 95% CIs were generated using Cox regression models. Overall, 205 160 patients were included. In the intent‐to‐treat analysis, over 188 551 and 188 678 person‐years of follow‐up (MI and stroke, respectively), there were 1077 MI and 968 stroke events. Initiation of SGLT‐2i vs oGLD was associated with a modestly lower risk of MI and stroke (MI: HR, 0.85; 95%CI, 0.72‐1.00; P = .05; Stroke: HR, 0.83; 95% CI, 0.71‐0.97; P = .02). These findings complement the results of the cardiovascular outcomes trials, and offer additional reassurance with regard to the cardiovascular effects of SGLT‐2i, specifically as it relates to ischaemic events. [ABSTRACT FROM AUTHOR]