Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Stent malapposition, strut coverage and atherothrombotic prolapse after percutaneous coronary interventions in ST-segment elevation myocardial infarction

Stent implantation in ST-segment elevation myocardial infarction (STEMI) patients can be challenging and sometimes associated with immediate and long-term suboptimal results. Stent malapposition and strut uncoverage, predictors of stent thrombosis, are frequently detected in STEMI patients at medium/long-term follow-up. Nevertheless, data at a short follow-up are missing. We aimed to assess the extent of stent malapposition and struts coverage in the subacute phase of STEMI after stent implantation in primary or rescue percutaneous coronary intervention (PCI)

CONTRAST MEDIUM INDUCED PD/PA RATIO (CMR) VERSUS FFR AND ADENOSINE-FREE INDEXES IN THE EVALUATION OF INTERMEDIATE CORONARY STENOSIS

Background The need for adenosine administration to achieve maximal hyperaemia limits the widespread application of fractional flow reserve (FFR) in the real world. We previously demonstrated that Pd/Pa ratio registered during submaximal reactive hyperaemia induced by conventional non-ionic radiographic contrast medium (contrast medium induced Pd/Pa ratio: CMR) can be sufficient for the assessment of physiological severity of stenosis in the majority of cases. In this study we aimed to test the accuracy of CMR in predicting an FFR 640.80 in comparison with other adenosine-free indexes, such as basal Pd/Pa and instantaneous wave-free ratio (iFR).Methods 450 patients with 532 intermediate coronary stenoses were prospectively and consecutively enrolled. FFR was measured after administration of adenosine, CMR was obtained after intracoronary injection of 6 ml of radiographic contrast medium, while Pd/Pa and iFR were measured at rest. Results Pd/Pa was measured in all 532 lesions, while CMR in 405 and iFR in 95. Although we found a significant correlation between FFR and all measured indexes, the strongest correlation was between FFR and CMR (r=0.89, p<0.001; r=0.73, p<0.001 for correlation between FFR and Pd/Pa; r=0.67, p<0.001 for correlation between FFR and iFR). ROC curve analysis confirmed these data, showing an excellent accuracy of CMR cut-off of 640.83 in predicting a positive FFR (AUC 0.97 [95% CI: 0.95-0.99], specificity 0.99, sensitivity 0.82). Moreover CMR was superior than basal Pd/Pa 640.92 (AUC 0.89 [95% CI: 0.86-0.92], specificity 0.84, sensitivity 0.80; p<0.001) and iFR 640.88 (AUC 0.92 [95% CI: 0.85-0.97], specificity 0.94, sensitivity 0.75; p=0.018) in predicting a positive FFR, and the two resting methods were not different (p=0.674). Conclusions in the present study we confirm in a much larger population our previously published data, showing that CMR is accurate in predicting the functional significance of coronary stenosis but also we demonstrate its superiority over other adenosine-free indexes (Pd/Pa and iFR), which moreover have the same power in predicting FFR. This finding support the use of CMR in clinical practice, limiting the use of adenosine to doubtful cases

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial

Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50\ue2\u80\u9375 years with type 2 diabetes inadequately controlled with metformin monotherapy (2\ue2\u80\u933 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15\ue2\u80\u9345 mg) or a sulfonylurea (5\ue2\u80\u9315 mg glibenclamide, 2\ue2\u80\u936 mg glimepiride, or 30\ue2\u80\u93120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57\uc2\ub73 months. The primary outcome occurred in 105 patients (1\uc2\ub75 per 100 person-years) who were given pioglitazone and 108 (1\uc2\ub75 per 100 person-years) who were given sulfonylureas (hazard ratio 0\uc2\ub796, 95% CI 0\uc2\ub774\ue2\u80\u931\uc2\ub726, p=0\uc2\ub779). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p<0\uc2\ub70001). Moderate weight gain (less than 2 kg, on average) occurred in both groups. Rates of heart failure, bladder cancer, and fractures were not significantly different between treatment groups. Interpretation In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin. Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events. Funding Italian Medicines Agency, Diabete Ricerca, and Italian Diabetes Society