Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Monitoring energy poverty in Northern Greece: the energy poverty phenomenon

The last two decades’ scientists have become increasingly interested in the aspects of energy poverty. In order to study the dynamics of energy poverty in Northern Greece a field study was carried out. The evidence presented is based on a comprehensive study of 350 questionnaires mainly for Western (47%) and Central Macedonia (45%), in Northern Greece. The questionnaire focused on the household’ and users’ characteristics, allowing for regional specific effects. Additionally, in an effort to study and quantify the relation between households’ net-income and the most common indicators of energy poverty a Chi-square test was estimated. At the same time six temperature and humidity loggers have been distributed to selected participants to record real-time data. Overall, the results of the survey unveiled that various characteristics of the domestic demand for heating are linked with the household’s net-income

Contribution to the hotel's building stock energy performance and environmental management

The present thesis concerns the potential and limitations of energy saving at the hotel sector. Hotel buildings are unique compared to other public, commercial buildings due to their varying size, their sheer number as well as their facilities and operating schedules. Every hotel needs to fulfill a number of criteria and adopt a certain “ifs” and “ands” in order to satisfy the demands of its users. Two of the important criteria emerging over the last decade refer to their environmental performance and energy efficiency. With a view to study the hotel’s energy and environmental performance, a top?down and a bottom?up analysis have been carried out. In a bottom – up approach, data related to the energy and environmental performance of buildings were gathered within a frame of a field study, along with information related to occupancy levels, indoor environmental quality and management procedures. The results of this study, and also of similar studies carried out and published over the last years; provide interesting in depth insights to the energy and environmental performance of specific hotels, or fairly limited groups of hotel buildings. At the same time, and in a top – down approach, data were obtained from the Hellenic National Statistical Service, as well as from the Greek Tourism Organization and Hotel Chambers. These data provide a reliable background in order to elaborate statistically reasonable mean and median values for the energy performance of various hotel groups. By combining the aforementioned data, the idea of a “typical” hotel derived. This was attempted by means of a control of the parameters determining the buildings’ energy performance, of the groups’ main features and of the statistical control of the variation, deviation and robustness of the data examined. Three typical hotels were created and simulated in order to study their energy performance for the elaboration of a master plan for the implementation of an energy renovation strategy.Η παρούσα εργασία πραγματεύεται το ζήτημα της εξοικονόμησης ενέργειας στον κτιριακό τομέα και ειδικότερα στις ξενοδοχειακές κατασκευές. Τα ξενοδοχεία αποτελούν μία ιδιαίτερη κατηγορία κτιρίων, σε σχέση με τα υπόλοιπα εμπορικά κτίρια, λόγω της μεγάλης ανομοιομορφίας των δραστηριοτήτων και λειτουργιών που πρέπει να περιλαμβάνουν. Κάθε ξενοδοχείο, στα πλαίσια ικανοποίησης των χρηστών και επισκεπτών του, ανάλογα με την κατηγορία του και την περίοδο λειτουργίας του, πρέπει να διαθέτει συγκεκριμένες παροχές, οι οποίες επηρεάζουν την περιβαλλοντική και ενεργειακή συμπεριφορά του. Παρ’ όλες τις προσπάθειες συνεχούς βελτίωσης της ποιότητας των παρεχόμενων υπηρεσιών, η πλειοψηφία των ξενοδοχειακών μονάδων στην Ελλάδα εξακολουθεί να αποτελείται από ξενοδοχεία 2 ή 3 αστέρων, εποχιακής λειτουργίας, με χαμηλές επιδόσεις στον τομέα της ενεργειακής και περιβαλλοντικής διαχείρισης. Σκοπός της συγκεκριμένης εργασίας είναι να παρουσιαστεί μία συνολική εικόνα του ξενοδοχειακού δυναμικού, και η εξέλιξη αυτού την τελευταία δεκαετία. Επομένως, για το σκοπό αυτό, αρχικά, συλλέχθηκαν και μελετήθηκαν δεδομένα από επιτόπια και ηλεκτρονική έρευνα αλλά και από το ελληνικό ξενοδοχειακό επιμελητήριο. Δημιουργήθηκαν ομάδες ξενοδοχείων μετά από στατιστική επεξεργασία των δεδομένων και συγκριτική τους μελέτη. Οι ομάδες αυτές αφορούσαν τα λειτουργικά τους χαρακτηριστικά, το μέγεθος τους αλλά και την τοποθεσία τους και οδήγησαν στην αναγνώριση τριών τυπικών ξενοδοχείων. Τα κτίρια των «τυπικών» ξενοδοχείων μελετήθηκαν προκειμένου να αποτιμηθεί η ενεργειακή τους απόδοση. Η αποτίμηση αυτή προέκυψε μέσω προσομοίωσης τους και επέτρεψε να προταθούν τεχνικές προτάσεις βελτίωσης της ενεργειακής και περιβαλλοντικής απόδοσης των ξενοδοχειακών τύπων, δεδομένων των τυπολογικών και κατασκευαστικών τους ιδιαιτεροτήτων

On the thermal characteristics and the mitigation potential of a medium size urban park in Athens, Greece

Δημοσίευση σε επιστημονικό περιοδικόSummarization: Measurements have been performed during summer in and around a medium size urban park located in the western part of Athens, Greece. Additional temperature data from 15 urban and suburban stations are used to perform comparative analysis at the city level. The park presents an important temperature inhomogeneity during both day and night. Average nocturnal cool island intensities against the reference urban stations varied between −0.7 K and −2.8 K, while during the daytime the average maximum cool island intensity (CII) was between −0.2 K and −2.6 K. A statistical significant correlation between the CII and the population density is found for both day and night. The park was warmer than the urban stations for ambient temperatures lower than 34 °C, while for higher urban temperatures the park was cooler and the absolute CII increased as a function of the ambient temperature. An important correlation with the wind speed is observed for wind speeds higher than 6 m/s. The mitigation potential of the park was assessed by performing three types of traverses around the park. The park cooling intensity was varying between 3.3 and 3.8 K, while the temperature gradient along the traverses changes as a function of the thermal properties of the urban areas and was between 0.2 and 1.4 K/100 m. The park cooling intensity presents a strong correlation with the wind speed for values higher than 5 m/s. The climatic influence of the park was extended up to 300 m from the borders of the park.Παρουσιάστηκε στο: Landscape and Urban Plannin

Energy efficiency in the hellenic building sector: an assessment of the restrictions and perspectives of the market

Summarization: The significance of bioclimatic architecture has become widely accepted since the 1970s and the implementation of its principles in practice is a key factor in order to achieve energy efficiency in the building sector. The way, however, from scientific acceptance to commercial utilization is not a straightforward one. This paper deals with the notion of bioclimatic architecture in buildings and investigates the aspects of this concept in Hellas. A sample of university researchers, building contractors and members of public organisations was interviewed using a standardised set of guidelines. The barriers to promoting bioclimatic design, role of the local government in the adoption process, level of environmental culture as well as perspectives of this concept in Hellas were the key areas of discussion in each of the interviews. The results from the data analysis reveal insufficient economic incentives, a lack in technical information as well as a lack in specific environmental policies that would foster the propagation of bioclimatic architecture.Presented on: Energy Polic

Dietary intake and major food sources of polyphenols in people with type 2 diabetes: The TOSCA.IT Study

none200nononeVitale, M.; Masulli, M.; Rivellese, A.A.; Bonora, E.; Cappellini, F.; Nicolucci, A.; Squatrito, S.; Antenucci, D.; Barrea, A.; Bianchi, C.; Bianchini, F.; Fontana, L.; Fornengo, P.; Giorgino, F.; Gnasso, A.; Mannucci, E.; Mazzotti, A.; Nappo, R.; Palena, A.P.; Pata, P.; Perriello, G.; Potenziani, S.; Radin, R.; Ricci, L.; Romeo, F.; Santini, C.; Scarponi, M.; Serra, R.; Timi, A.; Turco, A.A.; Vedovato, M.; Zavaroni, D.; Grioni, S.; Riccardi, G.; Vaccaro, O; Rivellese, Angela Albarosa; Cocozza, Sara; Auciello, Stefania; Turco, Anna Amelia; Bonora, Enzo; Cigolini, Massimo; Pichiri, Isabella; Brangani, Corinna; Tomasetto, Elena; Perriello, Gabriele; Timi, Alessia; Squatrito, Sebastiano; Sinagra, Tiziana; Longhitano, Sara; Tropea, Vanessa; Ballardini, Giorgio; Babini, Anna Carla; Ripani, Raffaella; Gregori, Giovanna; Dolci, Maria; Bruselli, Laura; Salutini, Isabella; Mori, Mary; Baccetti, Fabio; Lapolla, Annunziata; Sartore, Giovanni; Burlina, Silvia; Chilelli, Nino Cristiano; Buzzetti, Raffaella; Venditti, Chiara; Potenziani, Stella; Carlone, Angela; Galluzzo†, Aldo; Giordano, Carla; Torregrossa, Vittoria; Corsi, Laura; Cuneo, Giacomo; Corsi, Simona; Tizio, Biagio; Clemente, Gennaro; Citro, Giuseppe; Natale, Maria; Salvatore, Vita; Di Cianni, Graziano; Lacaria, Emilia; Russo, Laura; Iannarelli, Rossella; de Gregorio, Antonella; Sciarretta, Filomena; D’Andrea, Settimio; Montani, Valeria; Cannarsa, Emanuela; Dolcetti, Katia; Cordera, Renzo; Bonabello, Laura Affinito; Mazzucchelli, Chiara; Giorda, Carlo Bruno; Romeo, Francesco; Bonetto, Caterina; Antenucci, Daniela; Baldassarre, Maria Pompea Antonia; Iovine, Ciro; Nappo, Rossella; Ciano, Ornella; Dall’Aglio, Elisabetta; Mancastroppa, Giovanni; Grimaldi, Franco; Tonutti, Laura; Boemi, Massimo; D’Angelo, Federica; Leotta, Sergio; Fontana, Lucia; Lauro, Davide; Rinaldi, Maria Elena; Cignarelli, Mauro; la Macchia, Olga; Fariello, Stefania; Tomasi, Franco; Zamboni, Chiara; Dozio, Nicoletta; Trevisan, Roberto; Scaranna, Cristiana; Del Prato, Stefano; Miccoli, Roberto; Bianchi, Cristina; Garofolo, Monia; Pugliese, Giuseppe; Salvi, Laura; Rangel, Graziela; Vitale, Martina; Anichini, Roberto; Tedeschi, Anna; Corsini, Elisa; Cucinotta, Domenico; Di Benedetto, Antonino; Giunta, Loretta; Ruffo, Maria Concetta; Bossi, Antonio Carlo; Carpinter, Rita; Dotta, Francesco; Ceccarelli, Elena; Bartolo, Paolo Di; Caselli, Chiara; Luberto, Alessandra; Santini, Costanza; Mazzotti, Arianna; Calbucci, Giovanni; Consoli, Agostino; Ginestra, Federica; Calabrese, Maria; Zogheri, Alessia; Ricci, Lucia; Giorgino, Francesco; Laviola, Luigi; Ippolito, Claudia; Tarantino, Lucia; Avogaro, Angelo; Vedovato, Monica; Gnasso, Agostino; Carallo, Claudio; Scicchitano, Caterina; Zavaroni, Donatella; Livraga, Stefania; Perin, Paolo Cavallo; Forrnengo, Paolo; Prinzis, Tania; de Cosmo, Salvatore; Palena, Antonio Pio; Bacci, Simonetta; Mannucci, Edoardo; Lamanna, Caterina; Pata, Pietro; Lettina, Gabriele; Aiello, Antimo; Barrea, Angelina; Lalli, Carlo; Scarponi, Maura; Franzetti, Ivano; Radin, Raffaella; Serra, Rosalia; Petrachi, Francesca; Asprino, Vincenzo; Capra, Claudio; Cigolini, Massimo; Forte, Elisa; Potenziani, Stella; Reggiani, Giulio Marchesini; Forlani, Gabriele; Montesi, Luca; Mazzella, Natalia; Piatti, Pier Marco; Monti, Lucilla; Stuccillo, Michela; Auletta, Pasquale; Petraroli, Ettore; Capobianco, Giuseppe; Romano, Geremia; Cutolo, Michele; de Simone, Giosetta; Caiazzo, Gennaro; Nunziata, Peppe; Sorrentino, Susy; Amelia, Umberto; Calatola, Pasqualino; Capuano, GelsominaVitale, M.; Masulli, M.; Rivellese, A. A.; Bonora, Enzo; Cappellini, F.; Nicolucci, A.; Squatrito, S.; Antenucci, D.; Barrea, A.; Bianchi, C.; Bianchini, FRANCESCA ANTONIA; Fontana, L.; Fornengo, P.; Giorgino, FRANCESCO LIBERO; Gnasso, A.; Mannucci, E.; Mazzotti, Alfredo; Nappo, R.; Palena, A. P.; Pata, P.; Perriello, G.; Potenziani, S.; Radin, R.; Ricci, Laura; Romeo, Francesco; Santini, C.; Scarponi, M.; Serra, Roberto; Timi, A.; Turco, A. A.; Vedovato, M.; Zavaroni, D.; Grioni, S.; Riccardi, Giovanna; Vaccaro, O; Rivellese, Angela Albarosa; Cocozza, Sara; Auciello, Stefania; Turco, Anna Amelia; Bonora, Enzo; Cigolini, Massimo; Pichiri, Isabella; Brangani, Corinna; Tomasetto, Elena; Perriello, Gabriele; Timi, Alessia; Squatrito, Sebastiano; Sinagra, Tiziana; Longhitano, Sara; Tropea, Vanessa; Ballardini, Giorgio; Babini, Anna Carla; Ripani, Raffaella; Gregori, Giovanna; Dolci, Maria; Bruselli, Laura; Salutini, Isabella; Mori, Mary; Baccetti, Fabio; Lapolla, Annunziata; Sartore, Giovanni; Burlina, Silvia; Chilelli, NINO CRISTIANO; Buzzetti, Raffaella; Venditti, Chiara; Potenziani, Stella; Carlone, Angela; Galluzzo†, Aldo; Giordano, Carla; Torregrossa, Vittoria; Corsi, Laura; Cuneo, Giacomo; Corsi, Simona; Tizio, Biagio; Clemente, Gennaro; Citro, Giuseppe; Natale, Maria; Salvatore, Vita; Di Cianni, Graziano; Lacaria, Emilia; Russo, Laura; Iannarelli, Rossella; de Gregorio, Antonella; Sciarretta, Filomena; D’Andrea, Settimio; Montani, Valeria; Cannarsa, Emanuela; Dolcetti, Katia; Cordera, Renzo; Bonabello, Laura Affinito; Mazzucchelli, Chiara; Giorda, Carlo Bruno; Romeo, Francesco; Bonetto, Caterina; Antenucci, Daniela; Baldassarre, Maria Pompea Antonia; Iovine, Ciro; Nappo, Rossella; Ciano, Ornella; Dall’Aglio, Elisabetta; Mancastroppa, Giovanni; Grimaldi, Franco; Tonutti, Laura; Boemi, Massimo; D’Angelo, Federica; Leotta, Sergio; Fontana, Lucia; Lauro, Davide; Rinaldi, Maria Elena; Cignarelli, Mauro; la Macchia, Olga; Fariello, Stefania; Tomasi, Franco; Zamboni, Chiara; Dozio, Nicoletta; Trevisan, Roberto; Scaranna, Cristiana; Del Prato, Stefano; Miccoli, Roberto; Bianchi, Cristina; Garofolo, Monia; Pugliese, Giuseppe; Salvi, Laura; Rangel, Graziela; Vitale, Martina; Anichini, Roberto; Tedeschi, Anna; Corsini, Elisa; Cucinotta, Domenico; Di Benedetto, Antonino; Giunta, Loretta; Ruffo, Maria Concetta; Bossi, Antonio Carlo; Carpinter, Rita; Dotta, Francesco; Ceccarelli, Elena; Bartolo, Paolo Di; Caselli, Chiara; Luberto, Alessandra; Santini, Costanza; Mazzotti, Arianna; Calbucci, Giovanni; Consoli, Agostino; Ginestra, Federica; Calabrese, Maria; Zogheri, Alessia; Ricci, Lucia; Giorgino, FRANCESCO LIBERO; Laviola, Luigi; Ippolito, Claudia; Tarantino, Lucia; Avogaro, Angelo; Vedovato, Monica; Gnasso, Agostino; Carallo, Claudio; Scicchitano, Caterina; Zavaroni, Donatella; Livraga, Stefania; Perin, Paolo Cavallo; Forrnengo, Paolo; Prinzis, Tania; de Cosmo, Salvatore; Palena, Antonio Pio; Bacci, Simonetta; Mannucci, Edoardo; Lamanna, Caterina; Pata, Pietro; Lettina, Gabriele; Aiello, Antimo; Barrea, Angelina; Lalli, Carlo; Scarponi, Maura; Franzetti, Ivano; Radin, Raffaella; Serra, Rosalia; Petrachi, Francesca; Asprino, Vincenzo; Capra, Claudio; Cigolini, Massimo; Forte, Elisa; Potenziani, Stella; Reggiani, Giulio Marchesini; Forlani, Gabriele; Montesi, Luca; Mazzella, Natalia; Piatti, Pier Marco; Monti, Lucilla; Stuccillo, Michela; Auletta, Pasquale; Petraroli, Ettore; Capobianco, Giuseppe; Romano, Geremia; Cutolo, Michele; de Simone, Giosetta; Caiazzo, Gennaro; Nunziata, Peppe; Sorrentino, Susy; Amelia, Umberto; Calatola, Pasqualino; Capuano, Gelsomin

Dietary intake and major food sources of polyphenols in people with type 2 diabetes: The TOSCA.IT Study

Purpose: Proper evaluation of polyphenols intake at the population level is a necessary step in order to establish possible associations with health outcomes. Available data are limited, and so far no study has been performed in people with diabetes. The aim of this work was to document the intake of polyphenols and their major food sources in a cohort of people with type 2 diabetes and in socio-demographic subgroups. Methods: We studied 2573 men and women aged 50â\u80\u9375 years. Among others, anthropometry was measured by standard protocol and dietary habits were investigated by food frequency questionnaire (EPIC). The intake of polyphenols was evaluated using US Department of Agriculture and Phenol-Explorer databases. Results: The mean total polyphenol intake was 683.3 ± 5.8 mg/day. Non-alcoholic beverages represented the main food source of dietary polyphenols and provided 35.5% of total polyphenol intake, followed by fruits (23.0%), alcoholic beverages (14.0%), vegetables (12.4%), cereal products and tubers (4.6%), legumes (3.7%) and oils (2.1%); chocolate, cakes and nuts are negligible sources of polyphenols in this cohort. The two most important polyphenol classes contributing to the total intake were flavonoids (47.5%) and phenolic acids (47.4%). Polyphenol intake increased with age and education level and decreased with BMI; furthermore, in the northern regions of Italy, the polyphenol intake was slightly, but significantly higher than in the central or southern regions. Conclusions: The study documents for the first time the intake of polyphenols and their main food sources in people with diabetes using validated and complete databases of the polyphenol content of food. Compared with published data, collected in people without diabetes, these results suggest a lower intake and a different pattern of intake in people with diabetes

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