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.

In a 1-year T1D study, sotagliflozin combined with optimized insulin therapy was associated with sustained HbA reduction, weight loss, lower insulin dose, fewer episodes of severe hypoglycemia, improved patient-reported outcomes, and more DKA relative to placebo (ClinicalTrials.gov, NCT02384941).

These results demonstrate the agreement of the CGMS to blood glucose meter values, under conditions of home use, in patients selected by their physicians as candidates for continuous monitoring. The detailed glucose information provided by the CGMS should make successful management of diabetes more easily achieved.

Introduction: This trial assessed safety and effectiveness of an advanced hybrid closedloop (AHCL) system with automated basal (Auto Basal) and automated bolus correction (Auto Correction) in adolescents and adults with type 1 diabetes (T1D). Materials and Methods:This multi-center, single-arm study involved an intent to treat population of 157 individuals (39 adolescents aged 14-21 years and 118 adults aged ≥22-75 years) with T1D. Study participants used the MiniMed™ AHCL system during a baseline run-in period in which sensor-augmented pump +/-predictive low glucose management or Auto Basal was enabled for ~14 days. Thereafter, Auto Basal and Auto Correction were enabled for a study phase (~90 days), with glucose target set to 100mg/dL or 120mg/dL for ~45 days, followed by the other target for ~45 days. Study endpoints included safety events and change in mean A1C, time in range (TIR, 70-180mg/dL) and time below range (TBR, <70mg/dL). Run-in and study phase values were compared using Wilcoxon signedrank test a or paired t-test.Results: Overall group time spent in closed loop averaged 94.9±5.4% and involved only 1.2±0.8 exits/week. Compared to run-in, AHCL reduced A1C from 7.5±0.8% to 7.0±0.5% (<0.001 a , N=155), TIR increased from 68.8±10.5% to 74.5±6.9% (<0.001 a ) and TBR reduced from 3.3±2.9% to 2.3±1.7% (<0.001 a ). Similar benefits to glycemia were observed for each age group, and were more pronounced for the nighttime (12AM-6AM). The 100mg/dL target increased TIR to 75.4% (N=155), that was further optimized at a lower active insulin time setting (i.e. 2 hours), without increasing TBR. There were no severe hypoglycemia or diabetic ketoacidosis events during the study phase.Conclusions: These findings show that the MiniMed™ AHCL system is safe and allows for achievement of recommended glycemic targets in adolescents and adults with T1D.Adjustments in target and active insulin time settings may further optimize glycemia and improve user experience. a Wilcoxon signed-rank test.

The clinical course and outcomes of pediatric patients with fascicular VT and nonfascicular LV VT are varied. Catheter ablation procedures can be curative.

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Objective. Although many Fontan patients undergo pacemaker placement, there are few studies characterizing this population. Our purpose was to compare clinical characteristics, functional status and measures of ventricular performance in Fontan patients with and without a pacemaker. Patients and Design. The National Heart, Lung, and Blood Institute funded Pediatric Heart Network Fontan Cross‐Sectional Study characterized 546 Fontan survivors. Clinical characteristics, medical history and study outcomes (Child Health Questionnaire [CHQ]), echocardiographic evaluation of ventricular function, and exercise testing) were compared between subjects with and without pacemakers. Results. Of 71 subjects with pacemakers (13%), 43/71 (61%) were in a paced rhythm at the time of study enrollment (age 11.9 ± 3.4 years). Pacemaker subjects were older at study enrollment, more likely to have single left ventricles, and taking more medications. There were no differences in age at Fontan or Fontan type between the pacemaker and no pacemaker groups. There were no differences in exercise performance between groups. CHQ physical summary scores were lower in the pacemaker subjects (39.7 ± 14.3 vs. 46.1 ± 11.2, P =.001). Ventricular ejection fraction z‐score was also lower (−1.4 ± 1.9 vs. −0.8 ± 2.0, P =.05) in pacemaker subjects. Conclusions. In our cohort of Fontan survivors, those with a pacemaker have poorer functional status and evidence of decreased ventricular systolic function compared to Fontan survivors without a pacemaker.

Objectives Our aim was to examine the prevalence of arrhythmias and identify independent associations of time to arrhythmia development. Background Since introduction of the Fontan operation in 1971, long term results have steadily improved with newer modifications. However, atrial arrhythmias are frequent and contribute to ongoing morbidity and mortality. Data are lacking regarding the prevalence of arrhythmias and risk factors for their development in the current era. Methods The Pediatric Heart Network Fontan Cross-Sectional Study evaluated data from 7 centers, with 520 patients aged 6–18 years (mean 8.6±3.4 years after the Fontan operation), including echocardiograms, electrocardiograms, exercise testing, parent-reported Child Health Questionnaire (CHQ) results, and medical history. Results Supraventricular tachycardias were present in 9.4% of patients. Intra-atrial reentrant tachycardia (IART) was present in 7.3% (32/520). The hazard of IART decreased until 4–6 years post-Fontan, and then increased with age thereafter. Cardiac anatomy and resting heart rate (including marked bradycardia) were not associated with IART. We identified three independent associations of time to occurrence of IART: lower CHQ physical summary score (p<0.001); predominant rhythm (p=0.002; highest risk with paced rhythm), and type of Fontan operation (p=0.037; highest risk with atriopulmonary connection). Time to IART did not differ between patients with lateral tunnel and extracardiac conduit types of Fontan repair. Ventricular tachycardia was noted in 3.5% of patients. Conclusions Overall prevalence of IART was lower in this cohort (7.3%) than previously reported. Lower functional status, an atriopulmonary connection and paced rhythm were determined to be independently associated with development of IART after Fontan.