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.

To confirm non-inferiority of insulin degludec/insulin aspart (IDegAsp) once-daily (OD) versus insulin glargine (IGlar) U100 OD + insulin aspart (IAsp) OD for HbA 1c after 26 weeks, and compare efficacy and safety between groups at W26 + W38. Methods: A 38-week, randomised, open-label, treat-to-target (HbA 1c < 7.0%) trial in adults with type 2 diabetes mellitus (on basal insulin ± oral antidiabetic drugs; HbA 1c 7.0-10.0%). Randomisation (1:1): IDegAsp or IGlar U100 + IAsp. Intensification to IDegAsp twice daily (BID) was permitted at W26 + W32, or with additional IAsp injections at W26 (maximum IAsp BID) or W32 (maximum IAsp three-times daily). Results: For W0-W26, mean percentage-change (standard deviation) HbA 1c was: IDegAsp, À1.1 (0.9); IGlar U100 + IAsp, À1.1 (0.8); estimated treatment difference: 0.07% (95% confidence interval [CI]: À0.06; 0.21) confirmed non-inferiority. At W26 and W38, target HbA 1c achievement, and mean fasting and postprandial glucose were similar across groups. At W38, more subjects achieved target HbA 1c without hypoglycaemia with IDegAsp (22.5%) than with IGlar U100 + IAsp (21.1%), with significantly fewer nocturnal episodes (W0-W38, estimated rate ratio: 0.61 [95% CI: 0.40; 0.93]). Safety profiles were similar across treatment groups throughout. Conclusions: IDegAsp OD/BID are effective treatment intensification options versus multiple injection basal-bolus therapies, achieving similar glycaemic control, with significantly less nocturnal hypoglycaemia.