Evidence from routine clinical practice: EMPRISE provides a new perspective on CVOTs.

EMPA-REG OUTCOME is recognised by international guidelines as a landmark study that showed a significant cardioprotective benefit with empagliflozin in patients with type 2 diabetes (T2D) and cardiovascular disease. To assess the impact of empagliflozin in routine clinical practice, the ongoing EMPRISE study is collecting real-world evidence to compare effectiveness, safety and health economic outcomes between empagliflozin and DPP-4 inhibitors. A planned interim analysis of EMPRISE was recently published, confirming a substantial reduction in hospitalisation for heart failure with empagliflozin across a diverse patient population. In this commentary article, we discuss the new data in the context of current evidence and clinical guidelines, as clinicians experienced in managing cardiovascular risk in patients with T2D. We also look forward to what future insights EMPRISE may offer, as evidence is accumulated over the next years to complement the important findings of EMPA-REG OUTCOME.

CARMELINA: An important piece of the DPP-4 inhibitor CVOT puzzle.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of glucose-lowering agent for type 2 diabetes (T2D) that are commonly used in clinical practice. With the recent disclosure of data from the CARMELINA cardiovascular outcomes trial (CVOT), which investigated linagliptin, CV and renal outcomes data are now available for four agents in the DPP-4 inhibitor class that are approved in most markets. To consider how the CARMELINA study may be interpreted, and the relevance for our clinical practice, we convened as an expert group of diabetes specialists from the Central and Eastern Europe region to discuss the new disclosures. Our discussions revealed a general confidence in safety across the class that is further supported by CARMELINA. However, we also concluded that there are important differences in the available evidence level between agents in the setting of heart failure and data on renal outcomes. Here, we noted the clinical relevance to our practice of the study population in CARMELINA, which is unique among CVOTs in including a majority of patients with chronic kidney disease (CKD). Given the risk for future development of renal impairment that is associated with T2D even in patients without current overt CKD, we believe that the CARMELINA study provides important new insights that are clinically relevant for a broad range of patients. Finally, we discuss how these insights can be integrated into the approach to the pharmacotherapeutic management of hyperglycaemia that is recommended in newly updated guidelines.

Stroke in patients with diabetes mellitus.

The article's objective is to review the key advances in the scientific literature related to the association of stroke with diabetes mellitus and to summarize the current approaches to stroke prevention in diabetic patients. The key findings from the literature regarding stroke incidence in patients with diabetes, specific and nonspecific risk factors of stroke in the diabetic population, such as arterial hypertension, dyslipidemia, hyperglycemia, diabetes duration, diabetic complications, insulin resistance/hyperinsulinemia, course and outcome of stroke in subjects with diabetes and/or hyperglycemia, and the peculiarities of type, site and size of stroke in diabetic patients are discussed. The results of recent clinical trials aimed at correcting hyperglycemia, hypertension, and dyslipidemia, to prevent stroke in people with diabetes, are reviewed. The medical database Medline along with original articles from peer-reviewed journals were used for analysis. There is convincing evidence suggesting that diabetes mellitus represents a strong independent risk factor of stroke. The contribution of hyperglycemia to increased stroke risk is not proven. Data suggest an association of the full cluster of the insulin resistance syndrome and stroke. Diabetes is a risk factor mainly for ischemic stroke, while its association with hemorrhagic stroke remains controversial. Hyperglycemia is common in stroke patients, but it is not known whether it independently influences the course and outcome of stroke or merely reflects stroke severity and location. Aggressive control of arterial hypertension and dyslipidemia allows to decrease the risk of stroke in diabetic patients substantially, while the importance of glucose control for stroke prevention remains unproven.