Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Characteristics of Early Onset Nystagmus as a Presenting Sign of Optic Pathway Glioma in Infants

Optic pathway glioma (OPG) accounts for 25% of intra-cranial tumours during infancy. 25% of OPG affect the chiasm. In infancy, nystagmus may be the first and only sign of chiasmal OPG

Optic pathway gliomas: a review

Optic pathway gliomas account for 3-5% of all pediatric CNS tumors and represent the most common intrinsic optic nerve tumors. These tumors occur preferentially during the first decade of life and are particularly frequent in children with neurofibromatosis type 1. Although optic pathway gliomas are low-grade tumors, their behavior can be aggressive, and their management is often challenging. Their management includes observation, surgery, chemotherapy and radiation. The role of each modality is discussed as well as current and future developments in treatment, in particular targeted therapies that are currently being investigated

Visual Field Loss in Children With Sporadic and Neurofibromatosis Type 1 (NF1)-Associated Optic Pathway Gliomas: Baseline Characteristics From a Multicenter, Prospective Natural History Study

Prior retrospective studies, limited by selection bias and lack of standardization, have reported a high prevalence of visual field (VF) loss in children with both sporadic and neurofibromatosis type 1-associated optic pathway gliomas (NF1-OPGs). Here we report the feasibility of Goldmann kinetic perimetry (GVF) testing and detail baseline VF function in a cohort of children with and without neurofibromatosis type 1 (NF1) enrolled in a prospective multicenter OPG natural history study

Prevalence of Choroidal Abnormalities and Lisch Nodules in Children Meeting Clinical/ Molecular Diagnosis of NF1

Near infrared imaging shows bright patchy choroidal abnormalities (CA), thought to reflect choroidal neurofibromatosis-1 (NF1). This study aimed to determine the prevalence of CA and Lisch Nodules (LN) in children who met clinical diagnostic criteria (CDC) alone and those with a molecularly confirmed diagnosis (MCD) of NF1, and ascertain any differences between the group

Prevalence of Choroidal Abnormalities and Lisch Nodules in Children Meeting Clinical/ Molecular Diagnosis of NF1

Near infrared imaging shows bright patchy choroidal abnormalities (CA), thought to reflect choroidal neurofibromatosis-1 (NF1). This study aimed to determine the prevalence of CA and Lisch Nodules (LN) in children who met clinical diagnostic criteria (CDC) alone and those with a molecularly confirmed diagnosis (MCD) of NF1, and ascertain any differences between the group

Prevalence of Choroidal Abnormalities and Lisch Nodules in Children Meeting Clinical/ Molecular Diagnosis of NF1

Near infrared imaging shows bright patchy choroidal abnormalities (CA), thought to reflect choroidal neurofibromatosis-1 (NF1). This study aimed to determine the prevalence of CA and Lisch Nodules (LN) in children who met clinical diagnostic criteria (CDC) alone and those with a molecularly confirmed diagnosis (MCD) of NF1, and ascertain any differences between the group