ContextCombination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is important for treating type 2 diabetes (T2D). This trial assesses the efficacy and safety of semaglutide, a GLP-1RA, as an add-on to basal insulin.ObjectiveTo demonstrate the superiority of semaglutide vs placebo on glycemic control as an add-on to basal insulin in patients with T2D.DesignPhase 3a, double-blind, placebo-controlled, 30-week trial.SettingThis study included 90 sites in five countries.PatientsWe studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.InterventionsSubcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.Main Outcome MeasuresPrimary endpoint was change in glycated Hb (HbA1c) from baseline to week 30. Confirmatory secondary endpoint was change in body weight from baseline to week 30.ResultsAt week 30, mean HbA1c reductions [mean baseline value, 8.4% (67.9 mmol/mol)] with semaglutide 0.5 and 1.0 mg were 1.4% (15.8 mmol/mol) and 1.8% (20.2 mmol/mol) vs 0.1% (1.0 mmol/mol) with placebo [estimated treatment difference (ETD) vs placebo, –1.35 (14.8 mmol/mol); 95% CI, –1.61 to –1.10 and ETD, –1.75% (19.2 mmol/mol); 95% CI, –2.01 to –1.50; both P < 0.0001]. Severe or blood glucose–confirmed hypoglycemic episodes were reported in 11 patients (17 events) and 14 patients (25 events) with semaglutide 0.5 and 1.0 mg, respectively, vs seven patients (13 events) with placebo (estimated rate ratio vs placebo, 2.08; 95% CI, 0.67 to 6.51 and estimated rate ratio vs placebo, 2.41; 95% CI, 0.84 to 6.96 for 0.5 and 1.0 mg; both P = nonsignificant). Mean body weight decreased with semaglutide 0.5 and 1.0 mg vs placebo from baseline to end of treatment: 3.7, 6.4, and 1.4 kg (ETD, –2.31; 95% CI, –3.33 to –1.29 and ETD, –5.06; 95% CI, –6.08 to –4.04 kg; both P < 0.0001). Premature treatment discontinuation due to adverse events was higher for semaglutide 0.5 and 1.0 mg vs placebo (4.5%, 6.1%, and 0.8%), mainly due to gastrointestinal disorders.ConclusionsSemaglutide, added to basal insulin, significantly reduced HbA1c and body weight in patients with uncontrolled T2D vs placebo.

AimsTo evaluate diabetic retinopathy (DR) data from across the SUSTAIN clinical trial programme.Materials and methodsThe SUSTAIN clinical trial programme evaluated the efficacy and safety of semaglutide, a glucagon‐like peptide‐1 analogue, for the treatment of type 2 diabetes (T2D). In SUSTAIN 6, a 2‐year, pre‐approval cardiovascular outcomes trial, semaglutide was associated with a significant increase in the risk of DR complications (DRC) vs placebo. DR data from across the SUSTAIN trials were evaluated, and post hoc analyses of the SUSTAIN 6 data were conducted. These included subgroup analyses to identify at‐risk patients and a mediation analysis with initial change in glycated haemoglobin (HbA1c; percentage‐points at week 16) as a covariate, to examine the role of the magnitude of reduction in HbA1c as an intermediate factor affecting risk of DRC.ResultsThere was no imbalance in DR adverse events across the SUSTAIN 1 to 5 and Japanese trials. The majority of the effect with semaglutide vs placebo in SUSTAIN 6 may be attributed to the magnitude and rapidity of HbA1c reduction during the first 16 weeks of treatment in patients who had pre‐existing DR and poor glycaemic control at baseline, and who were treated with insulin.ConclusionsEarly worsening of DR is a known phenomenon associated with the rapidity and magnitude of improvement in glycaemic control with insulin; the DRC findings in SUSTAIN 6 are consistent with this. Guidance regarding the early worsening of DR is recommended with insulin. Similar recommendations may be appropriate for semaglutide.

SummaryWe prospectively compared two point-of-care haemoglobin concentration measuring devices with laboratory measurements to determine their accuracy in women undergoing caesarean section delivery. The two devices were the Masimo Rainbow SET Ò Radical -7 TM pulse co-oximeter and the HemoCue Ò HB 201+, which is a cuvette-type system that uses photometry. Co-oximeter readings and HemoCue measurements were taken before and after surgery, and compared with laboratory measurements of haemoglobin concentration taken at the same time. We analysed data from 137 patients using Bland-Altman plots. Limits of agreement for co-oximeter readings were )4.20 to 2.02 g.dl )1 and for HemoCue were )1.49 to 1.48 g.dl )1 . The bias (mean difference) for the co-oximeter was )1.09 g.dl )1 (95% CI )1.28 to )0.91) and for the HemoCue was )0.001 g.dl )1 (95% CI )0.089 to 0.088). Overall, 110 ⁄ 274 (40%) co-oximeter readings were within 1 g.dl

The efficacy and safety of semaglutide vs comparators in non‐elderly (<65 years) and elderly (≥65 years) patients with type 2 diabetes (T2D) across the SUSTAIN 1‐5 trials were evaluated. Patients were randomized to once‐weekly subcutaneous semaglutide (0.5 or 1.0 mg) vs placebo, sitagliptin, exenatide or insulin. The primary objective was change in HbA1c and secondary objectives were changes in body weight and safety. Mean HbA1c decreased from baseline by 1.2%‐1.5% and 1.5%‐1.9% vs 0%‐0.9% (non‐elderly, n = 3045) and by 1.3%‐1.5% and 1.2%‐1.8% vs 0.2%‐1.0% (elderly, n = 854) with semaglutide 0.5 and 1.0 mg vs comparators. Similar reductions from baseline in mean body weight with semaglutide occurred in both age groups. Similar proportions of patients experienced adverse events; premature treatment discontinuations were higher in elderly vs non‐elderly patients. No increased risk of severe or blood glucose‐confirmed hypoglycaemia was seen with semaglutide vs comparators between age groups. Semaglutide had a comparable efficacy and safety profile in non‐elderly and elderly patients across the SUSTAIN 1‐5 trials, making it an effective treatment option for elderly patients with T2D.

NCT02065219.