ESPE Yearbook of Paediatric Endocrinology

N Engl J Med. 2021;385(20):1868-80. doi: 10.1056/NEJMoa2035790. PubMed ID: 34758253Brief summary: This paper describes the pilot data for the UK 100 000 Genomes Project, including Whole Genome Sequencing (WGS) data on 4660 participants from 2183 families, and covering 161 disorders. They made a genetic diagnosis in 25% of probands; diagnoses were more likely for probands who presented with inte...

To read the full abstract: Lancet 2017;389:2473-2481We are all familiar with the ‘placebo’ effect, when the psychological anticipation of a ‘benefit’ of treatment is so strong that it adds to or even outweighs the actual physical benefits. Many doctors have even admitted to prescribing placebo tablets, or “sugar pills” to their patients, for exam...

N Engl J Med. 2021;385(6):503-15. doi: 10.1056/NEJMoa2107519.PubMed ID: 34170647Brief summary: this randomized control trial in 1879 adults with type 2 diabetes compared effects of once-weekly Tirzepatide (5, 10 or 15 mg) versus once-weekly Semaglutide (1 mg) on glycemic control. After 40 weeks, all doses of Tirzepatide were superior to Semaglutide on lowering HbA1c.Gluca...

To read the full abstract: N Engl J Med. 2020;382(22):2117–2128. doi: https://pubmed.ncbi.nlm.nih.gov/32233338/Kelly et al. randomly assigned (1:1) n =251 obese adolescents (age 12 to <18 years) to receive either liraglutide (3.0 mg), a long-acting glucagon-like peptide-1 agonist, or placebo subcutaneously once daily in addition to lifestyle therapy. Liraglutide w...

To read the full abstract: N Engl J Med 2019;380:1235–1246This paper reports a randomized, double-blind, placebo-controlled, phase 3 trial of darolutamide, a novel oral androgen-receptor antagonist, in 1509 men with non-metastatic, castration-resistant prostate cancer. Median metastasis-free survival was significantly longer with darolutamide (40.4 months) than placebo (18.4 ...

Brief summary: This phase 3 double-blind, parallel-group, randomized, placebo-controlled trial over 68 weeks randomised (2:1) 201 adolescents with obesity to receive semaglutide 2.4 mg once weekly or placebo. Both groups also received lifestyle intervention. The primary endpoint was the percentage change in BMI. Treatment with semaglutide produced clinically relevant reductions in BMI and body weight, and improvements in cardiovascular risk factors, which were all significantl...

Brief summary: This randomized, double-blind, phase 3 trial of youths with inadequately controlled T2D, dulaglutide treatment was superior to placebo in reducing the glycated hemoglobin level at 26 weeks.Comment: T2D in children and adolescents is an aggressive disease with early onset of complications, leading to significant morbidity and mortality. After three decades with no efficient treatment, there is finally light at the end of the tunnel.<p c...

To read the full abstract: N Engl J Med 2017;377:633-643Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates levels of plasma LDL-C by interacting with the LDL receptor. After binding and internalization, PCSK9 directs the LDL receptor to lysosomal degradation and inhibits its recycling to the cell surface, and thus accelerates the degradation of hepatic LDL receptors. This reduces the ...

Lancet Diabetes Endocrinol. 2020 Dec;8(12):960–970.https://pubmed.ncbi.nlm.nih.gov/33137293/This article reports the results of two single-arm, open-label, multicentre, phase 3 trials of the MC4R agonist, setmelanotide, in patients with severe obesity due to pro-opiomelanocortin (POMC) deficiency or leptin receptor (LEPR) deficiency. Mean % change in bodyweight after ~1 year was &#8722...

Brief summary: In this double-blind, randomized, placebo-controlled trial, bempedoic acid (Nexletol) reduced the incidence of a composite cardiovascular.Comment: Bempedoic acid is an ATP citrate lyase inhibitor. ATP citrate lyase catalyses the conversion of citrate to acetyl-CoA, the fundamental substrate required for the synthesis of cholesterol and fatty acids. By inhibiting the cholesterol synthesis pathway, bempedoic acid reduces intra-hepatic LDL-C....