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Background Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment. Methods This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30-59 mL/min per 1•73 m², and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA1c (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete.

Background: Decompensated heart failure patients are characterised by functional dependence and low exercise tolerance. Aerobic exercise can improve symptoms, functional capacity and an increase in exercise tolerance. However, the benefits of early rehabilitation have not yet been validated. Objective: To evaluate the safety and feasibility of an aerobic exercise training programme in functional capacity of decompensated heart failure patients. Methodology: A single centre, parallel, randomised controlled, open label trial, with 100 patients. The training group (TG, n=50) performed the training protocol and the control group (CG, n=50) performed the usual rehabilitation procedures. The London chest activity of daily living (LCADL) scale, the Barthel index (BI) and the 6 minute walking test (6MWT) at discharge were used to evaluate the efficacy of the protocol. Safety was measured by the existence of adverse events. Results: The mean age of the patients was 70 years, 20% were New York Heart Association (NYHA) class IV and 80% NYHA class III at admission. The major heart failure aetiology was ischaemic (35 patients) and valvular disease (25 patients). There were no significant differences between groups at baseline in terms of sociodemographic or pathophysiological characteristics. There was a statistically significant difference of 54.2 meters for the training group ( P=0.026) in the 6MWT and at LCADL 12 versus 16 ( P=0.003), but the BI did not: 96 versus 92 ( P=0.072). No major adverse events occurred. Conclusions: The training protocol demonstrated safety and efficacy, promoting functional capacity. This study elucidated about the benefits of a systematised implementation of physical exercise during the patient’s clinical stabilisation phase, which had not yet been demonstrated. Trial registration: Clinicaltrials.gov NCT03838003, URL: https://clinicaltrials.gov/ct2/show/NCT03838003 .

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