Elevated hemoglobin A_1c (HbA_1c) values correlate with microvascular and macrovascular complications. Thus, patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing macrovascular events. Treatment of T2DM should be based on a multifactorial approach because of its evidence regarding reduction of macrovascular complications and mortality in T2DM. It is well known that intensive glucose control reduces the risk of microvascular complications in T2DM, but the effects of antidiabetic drugs on macrovascular complications and mortality in T2DM are less clear. The results of recent trials have demonstrated clear evidence that empagliflozin and liraglutide reduce cardiovascular (CV) and all-cause mortality in T2DM, an effect that is absent in other members of antidiabetic drugs. Empagliflozin is a member of a novel class of antidiabetic drugs, the sodium–glucose co-transporter 2 (SGLT2) inhibitors. Two ongoing randomized clinical trials involving other SGLT2 inhibitors, canagliflozin and dapagliflozin, will provide additional evidence of the beneficial effects of SGLT2 inhibitors in T2DM population. The aim of this paper is to systematically present the latest evidence regarding the usage of antidiabetic drugs, and the reduction of macrovascular complications and mortality. A special emphasis is put on the novel class of antidiabetic drugs, of SGLT2 inhibitors.

BRCA1/2 mutations and homologous recombination deficiency (HRD) predispose to increased sensitivity to poly(ADP-ribose)polymerase (PARP) inhibitor treatment. Our aim was to evaluate the PARP inhibitors effect on progression free survival (PFS) in a subpopulation with homologous recombination proficient status (HRD-BRCA-). A systematic literature search was performed for all studies reporting on the effect of PARP inhibitors regarding PFS in the HRD-BRCA- subpopulation, in patients with epithelial ovarian, tubal or primary peritoneal cancers (EOC). Five studies were included, enrolling a population of 3413 patients, with 1070 of them being HRD-BRCA-. PARP inhibitors were effective in the treatment of EOC, regardless of HRD and BRCA status or line of therapy. The estimated pooled effect hazard ratio (HR), assessing PFS for PARP inhibitors compared with control, was 0.76 (95% CI: 0.65–0.88, I² = 46%) in the HRD-BRCA- subpopulation. Comparing both subpopulations with HRD positive status (HRD+ BRCA+, HRD+ BRCA-) versus the HRD-BRCA-subpopulation, we have found statistically significant differences in the effect on PFS (P < 0.05 for every interaction test) favouring HRD positive subpopulations (HRD+ BRCA+, HRD+ BRCA-). In the HRD-BRCA- subpopulation of patients, PARP inhibitors used as the second- or later-line of therapy showed more pronounced effect then when given as first line treatment (P = 0.04). Treatment of EOC with PARP inhibitors showed a significant effect regarding PFS in the HRD-BRCA- subpopulation, although a much higher benefit was evident for patients with HRD+ status (HRD+ BRCA+ and HRD+ BRCA-). In the HRD- subpopulation second line PARP inhibitor treatment showed greater benefit compared to first line PARP inhibitor treatment.

Aim Type 2 diabetes (T2D) is one of the major public health issues worldwide. The main cause of mortality and morbidity among T2D patients are cardiovascular (CV) causes. Various antidiabetics are used in T2D treatment, but until recently they lacked clear evidence of the reduction in CV mortality and all‐cause mortality as independent study end‐points. The aim of this article was to present and critically evaluate potential mechanisms behind the remarkable results documented in trials with new antidiabetics for the treatment of T2D. Methods Relevant data were collected using the MEDLINE, PubMed, EMBASE, Web of Science, Science Direct, and Scopus databases with the key words: “type 2 diabetes,” “mortality,” “glucagon,” “empagliflozin,” “liraglutide,” “insulin” and “QTc.” Searches were not limited to specific publication types or study designs. Results The EMPA‐REG OUTCOME trial with empagliflozin and LEADER trial with liraglutide presented remarkable results regarding the reduction in mortality in T2D treatment. However, the potential mechanism for those beneficial effects is difficult to determine. It is not likely that improvements in classic CV risk factors are responsible for the observed effect. A potential mechanism may be caused by the elevation of postprandial (PP) glucagon concentrations that can be seen with an empagliflozin and liraglutide therapy, which could have beneficial effects considering the myocardial electrical stability in T2D patients. Conclusion This hypothesis throws new light upon possible mechanisms of reduction in mortality in T2D patients.

To the Editor We have read recently published articles investigating the correlation between the use of aspirin and lower incidence of ovarian and hepatocellula