Effects of the dual sodium-glucose linked transporter inhibitor, licogliflozinvsplacebo or empagliflozin in patients with type 2 diabetes and heart failure

Aims Explore the efficacy, safety and tolerability of the dual sodium-glucose cotransporter (SGLT) 1 and 2 inhibitor, licogliflozin in patients with type-2 diabetes mellitus (T2DM) and heart failure. Methods This multicentre, parallel-group phase IIA study randomized 125 patients with T2DM and heart failure (New York Heart Association II-IV; plasma N-terminal pro b-type natriuretic peptide [NT-proBNP] >300 pg/mL) to licogliflozin (2.5 mg, 10 mg, 50 mg) taken at bedtime, empagliflozin (25 mg) or placebo (44 patients completed the study). The primary endpoint was change from baseline in NT-proBNP after 12 weeks. Secondary endpoints included change from baseline in glycated haemoglobin, fasting plasma glucose, weight, blood pressure, fasting lipid profile, high-sensitivity c-reactive protein, and safety and tolerability. Results Licogliflozin 10 mg for 12 weeks significantly reduced NT-proBNPvsplacebo (Geometric mean ratio 0.56 [95% confidence interval: 0.33, 0.95],P =.033). A trend was observed with 50 mg licogliflozin (0.64 [95% confidence interval: 0.40, 1.03],P =.064), with no difference between licogliflozin and empagliflozin. The largest numerical decreases in glycated haemoglobin were with licogliflozin 50 mg (-0.58 +/- 0.34%) and empagliflozin (-0.44 +/- 1.18%)vsplacebo (-0.04 +/- 0.91%). The reduction in body weight was similar with licogliflozin 50 mg (-2.15 +/- 2.40 kg) and empagliflozin (-2.25 +/- 1.89 kg). A numerical reduction in systolic blood pressure was seen with licogliflozin 50 mg (-9.54 +/- 16.88 mmHg) and empagliflozin (-6.98 +/- 15.03 mmHg)vsplacebo (-2.85 +/- 11.97 mmHg). Adverse events (AEs) were mild, including hypotension (6.5%), hypoglycaemia (8.1%) and inadequate diabetes control (1.6%). The incidence of diarrhoea (4.9%) was lower than previously reported. Conclusion The reduction in NT-proBNP with licogliflozin suggests a potential benefit of SGLT1 and 2 inhibition in patients with T2DM and heart failure

Exploring early combination strategy in Latin American patients with newly diagnosed type 2 diabetes : a sub-analysis of the VERIFY study

Background Patients with type 2 diabetes mellitus (T2DM) from Latin American countries face challenges in access to healthcare, leading to under-diagnosis, under-achievement of glycemic target, and long-term complications. Early diagnosis and treatment initiation are of paramount importance in this population due to the high prevalence of risk factors such as obesity and metabolic syndrome. The VERIFY study in patients with newly diagnosed T2DM (across 34 countries), assessed the normoglycemic durability (5 years), with early combination (EC) therapy approach versus the traditional stepwise approach of initiating treatment with metformin monotherapy (MET). Here we present the results from the VERIFY study for participants from eight countries in Latin America. Methods Newly diagnosed adult patients with T2DM, HbA1c 6.5-7.5% and body-mass index (BMI) of 22-40 kg/m(2) were enrolled. The primary endpoint was time to initial treatment failure (TF; HbA1c >= 7.0% at two consecutive scheduled visits 13 weeks apart). Time to second TF was evaluated when patients in both groups were receiving and failing on the vildagliptin combination. Safety and tolerability were also assessed for both treatment approaches during the study. Results A total of 537 eligible patients (female, 58.8%) were randomly assigned to receive either EC (n = 266) or MET (n = 271). EC significantly reduced the relative risk of time to initial TF by 47% versus MET [HR (95% CI) 0.53 (0.4, 0.7) p < 0.0001]. Overall, 46.4% versus 66.3% of patients achieved the primary endpoint in the EC and MET groups, with a median [interquartile range (IQR)] time to TF of 59.8 (27.5, not evaluable) and 33.4 (12.2, 60.1) months, respectively. The risk for time to second TF was 31% lower with EC (p < 0.0092). A higher proportion of patients receiving EC maintained durable HbA1c < 7.0%, < 6.5%, and < 6.0%. Both treatment approaches were well tolerated, and only 3.2% of participants discontinued the study due to adverse events. All hypoglycemic events (EC: n = 7 and MET: n = 3) were single, mild episodes and did not lead to study discontinuation. Conclusion Similar to the global population, long-term clinical benefits were achieved more frequently and without tolerability issues with EC versus standard-of-care MET in this Latin American sub-population. This study is registered with ClinicalTrials.gov, NCT01528254.Peer reviewe

A pre-specified statistical analysis plan for the VERIFY study : Vildagliptin efficacy in combination with metformin for early treatment of T2DM

Aims To ensure the integrity of the planned analyses and maximize the clinical utility of the VERIFY study results by describing the detailed concepts behind its statistical analysis plan (SAP) before completion of data collection and study database lock. The SAP will be adhered to for the final primary data analysis of the VERIFY trial. Materials and Methods Vildagliptin efficacy in combination with metformin for early treatment of T2DM (VERIFY) is an ongoing, multicentre, randomized controlled trial aiming to demonstrate the clinical benefits of glycaemic durability and glucose control achieved with an early combination therapy in newly-diagnosed type 2 diabetes (T2DM) patients. Results The SAP was initially designed at the study protocol conception phase and later modified, as reported here, in collaboration between the steering committee members, statisticians, and the VERIFY study leadership team. All authors were blinded to treatment allocation. An independent statistician has additionally retrieved and presented unblinded data to the independent data safety monitoring committee. An overview of the trial design with a focus on describing the fine-tuning of the analysis plan for the primary efficacy endpoint, risk of initial treatment failure, and secondary, exploratory and pre-specified subgroup analyses is provided here. Conclusion According to optimal trial practice, the details of the statistical analysis and data-handling plan prior to locking the database are reported here. The SAP accords with high-quality standards of internal validity to minimize analysis bias and will enhance the utility of the reported results for improved outcomes in the management of T2DM.Peer reviewe

Long-Term Glycaemic Durability of Early Combination Therapy Strategy versus Metformin Monotherapy in Korean Patients with Newly Diagnosed Type 2 Diabetes Mellitus

We assessed the glycaemic durability with early combination (EC; vildagliptin+metformin [MET], n=22) versus MET monotherapy (n=17), among newly-diagnosed type 2 diabetes mellitus (T2DM) enrolled (between 2012 and 2014) in the VERIFY study from Korea (n=39). Primary endpoint was time to initial treatment failure (TF) (glycosylated hemoglobin [HbA1c]>= 7.0% at two consecutive scheduled visits after randomization [end of period 1]). Time to second TF was assessed when both groups were receiving and failing on the combination (end of period 2). With EC the risk of initial TF significantly reduced by 78% compared to MET (n=3 [15%] vs. n=10 [58.7%], P=0.0228). No secondary TF occurred in EC group versus five patients (29.4%) in MET. Patients receiving EC treatment achieved consistently lower HbA1c levels. Both treatment approaches were well tolerated with no hypoglycaemic events. In Korean patients with newly diagnosed T2DM, EC treatment significantly and consistently improved the long-term glycaemic durability as compared with MET.Peer reviewe

Assessment of energy and business performance of innovative technologies in SMEs

A major target of the European Green Deal is to raise the 2030 greenhouse gas emission reduction target to 55% compared to 1990. This high ambition includes an increase of the energy performance of buildings and additional generation of renewable energy in all sectors. The tertiary sector, including small and medium sized enterprises (SMEs) such as butchers, small food and non-food shops, restaurants and pubs, is one of the sectors that can contribute to this goal. While large companies in this sector are regularly in the news with iconic projects, for many SME owners “sustainability” is not a key issue. Reasons are that 1) they are not aware of interesting technologies or business cases specific for their company, 2) they are focused on their own business operation and 3) do not always own the building. That is why the Flemish-Dutch TERTS project strives for a transition in energy use and production by 1) demonstrating cutting-edge (innovative) technologies (e.g. circular isolation materials, heat pumps etc.) in SMEs and 2) by guiding these SMEs. This study assesses the impact of different (innovative) technologies specific for the target group ‘barber shops’. A reference building is made by analysing 60 existing barber shops in Flanders. The energy use of the barber shop including the systems is calculated according to DIN V 18599 using the Energieberater 18 599 3D PLUS. Subsequently, the costbenefit of various measures is calculated and compared. This provides us with an approach that not only includes financial measures but also takes metrics into account for CO2 reduction and comfort. Several technologies, which only have moderate financial benefits, reach acceptable overall satisfaction due to the inclusive metrics. This approach is based on modern business model developments and offer SMEs a more qualitative and inclusive way of the return of innovative technologies to support their investment decision making

FTY720 combined with tacrolimus in de novo renal transplantation: 1-year, multicenter, open-label randomized study

Background. FTY720 (fingolimod), a novel immunomodulator, has demonstrated potential for prevention of acute rejection in combination with cyclosporine.Methods. This study evaluated FTY720 2.5 mg versus mycophenolate mofetil (MMF) in a combination regimen with standard tacrolimus and corticosteroids in de novo renal transplant recipients for the composite efficacy within 6 months of transplantation.Results. Incidence of treated biopsy-proven acute rejection was 22.9% with FTY720 and 18.5% with MMF. Increased incidence of macular oedema, transient decrease in heart rate and low rate of infections were seen in the FTY720 arm.Conclusion. FTY720 combined with tacrolimus and steroids did not show a significant therapeutic advantage over MMF for the prevention of acute rejection in de novo renal transplant recipients. © The Author 2011. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe