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Interest in evidence-based medicine (EBM) is growing in Italy, although its impact upon health policies and clinical practice is unclear. Rather than getting health information from unbiased evidence-based sources, doctors [...]

Abstract Background In an effort to ensure that all physicians have access to valid and reliable evidence on drug effectiveness, the Italian Drug Agency sponsored a free-access e-learning system, based on Clinical Evidence, called ECCE. Doctors have access to an electronic version and related clinical vignettes. Correct answers to the interactive vignettes provide Continuing Medical Education credits. The aims of this trial are to establish whether the e-learning program (ECCE) increases physicians' basic knowledge about common clinical scenarios, and whether ECCE is superior to the passive diffusion of information through the printed version of Clinical Evidence. Design All Italian doctors naïve to ECCE will be randomised to three groups. Group one will have access to ECCE for Clinical Evidence chapters and vignettes lot A and will provide control data for Clinical Evidence chapters and vignettes lot B; group two vice versa; group three will receive the concise printed version of Clinical Evidence. There are in fact two designs: a before and after pragmatic trial utilising a two by two incomplete block design (group one versus group two) and a classical design (group one and two versus group three). The primary outcome will be the retention of Clinical Evidence contents assessed from the scores for clinical vignettes selected from ECCE at least six months after the intervention. To avoid test-retest effects, we will randomly select vignettes out of lot A and lot B, avoiding repetitions. In order to preserve the comparability of lots, we will select vignettes with similar, optimal psychometric characteristics. Trial registration ISRCTN27453314

The 2019 ESC-EASD guidelines provide recommendations for CV risk assessment and medical treatment in diabetic patients. Three CV risk categories were originally defined: 1) very high risk, 2) high risk and 3) moderate risk according to the presence of CVD, other target organ damage (proteinuria, renal impairment defined as eGFR ≥ 30 mL/min/1.73 m2, left ventricular hypertrophy, retinopathy), duration of disease, age, risk factors (hypertension, dyslipidemia, smoking, obesity). In very high risk CV category SGLT2-I and GLP1-RA were identify as treatment of choice. Based on these criteria, we developed the web APP "AWARE", an application software which runs on a web server and is accessed via internet browser. From November 10th 2020 to January 10th 2021 we employed AWARE as a tool to assess CV risk of 650 type 2 diabetes patients in clinical practice. The APP was implemented with additional features such as HbA1c and therapy. Of the 650 subjects examined, 430 were very high risk (66%), 73 (11,2%) high risk, 5 (0,8%) at moderate risk while 145 patients (22%) didn't match with any of these categories. We allocated these patients into an additional "undetermined risk" category. Median HbA1c in all subjects was 7.2±1.14 (7,3±1.15% in very high risk category, 7.2±1.15% in high risk category, 6,2±0.41% in moderate risk and 6.9±1.12% in "undetermined" risk). In the very high risk category CVD was present in 166 subject (38%), duration of disease>10 aa in 238 subjects (55%), proteinuria in 53 subjects (12%) (p=0.000 vs. all other categories). Either SGLT2-I or GLP1-RA were prescribed in 30% of patients in the very high risk category. The APP "AWARE" in useful to identify CV risk in diabetic. The classification according to the criteria of 2019 ESC/EASD guidelines does not includes 22% of patients in clinical practice. Around 70% of patients in the very high CV risk category are not treated with the optimal drug therapy suggested by the 2019 ESC/EASD guidelines. Disclosure: C. C. Berra: None. R. Manfrini: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Mundipharma International, Novo Nordisk, Sanofi. R. Ghelardi: None. P. M. Bollati: None. L. Bucciarelli: None. M. Mirani: None. M. Muratori: None. F. Folli: None. Aware study group: n/a. [ABSTRACT FROM AUTHOR]

Simultaneous activation of the incretin G-protein-coupled receptors (GPCRs) via unimolecular dual-receptor agonists (UDRA) has emerged as a new therapeutic approach for type 2 diabetes. Recent studies also advocate triple agonism with molecules also capable of binding the glucagon receptor. In this scoping review, we discuss the cellular mechanisms of action (MOA) underlying the actions of these novel and therapeutically important classes of peptide receptor agonists. Clinical efficacy studies of several UDRAs have demonstrated favorable results both as monotherapies and when combined with approved hypoglycemics. Although the additive insulinotropic effects of dual glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic peptide receptor (GIPR) agonism were anticipated based on the known actions of either glucagon-like peptide-1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP) alone, the additional benefits from GCGR were largely unexpected. Whether additional synergistic or antagonistic interactions among these G-protein receptor signaling pathways arise from simultaneous stimulation is not known. The signaling pathways affected by dual- and tri-agonism require more trenchant investigation before a comprehensive understanding of the cellular MOA. This knowledge will be essential for understanding the chronic efficacy and safety of these treatments.