Metreleptin
Sources réglementaires consultées
Contre-indications
Absolues
- Obésité commune ; hypersensibilité connue au produit.
Mises en garde cliniques
- Mise en garde encadrée · Avertissement encadre: des anticorps neutralisants et des lymphomes ont ete rapportes; une prescription et un suivi specialise sont requis. — FDA MYALEPT prescribing information
- Mise en garde majeure · Peut provoquer une hypoglycemie, surtout avec un traitement antidiabetique concomitant; revoir le plan avec l'equipe soignante. — FDA MYALEPT prescribing information
Interactions médicamenteuses
- ModéréeSubstrats du CYP450
Mécanisme: Les modifications d'exposition au CYP peuvent necessiter une surveillance et un ajustement par l'equipe soignante.
Recommandation: La coadministration requiert l'evaluation de l'equipe soignante.
FDA MYALEPT prescribing information
Grossesse et allaitement
Pendant la grossesse, evaluer le benefice et le risque avec l'equipe specialisee; ne pas arreter ni commencer sans indication clinique.
Bibliographie récente (PubMed)
Obesity is an epidemic and a public health threat. Medical weight management remains one of the options for the treatment of excess weight and recent advances have revolutionized how we treat, and more importantly how we will be treating obesity in the near future. Metreleptin and Setmelanotide are currently indicated for rare obesity syndromes, and 5 other medications (orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, semaglutide) are approved for non-syndromic obesity. Tirzepatide is about to be approved, and other drugs, with exciting novel mechanisms of action primarily based on incretins, are currently being investigated in different phases of clinical trials. The majority of these compounds act centrally, to reduce appetite and increase satiety, and secondarily, in the gastrointestinal tract to slow gastric emptying. All anti-obesity medications improve weight and metabolic parameters, with variable potency and effects depending on the specific drug. The currently available data do not support a reduction in hard cardiovascular outcomes, but it is almost certain that such data are forthcoming in the very near future. The choice of the anti-obesity medication needs to take into consideration the patient's clinical and biochemical profile, co-morbidities, and drug contra-indications, as well as expected degree of weight loss and improvements in cardio-renal and metabolic risk. It also remains to be seen whether precision medicine may offer personalized solutions to individuals with obesity, and whether it may represent the future of medical weight management along with the development of novel, very potent, anti-obesity medications currently in the pipeline. None.
Eating disorders (EDs) are common mental health conditions that carry exceedingly high morbidity and mortality rates. Evidence-based treatment options include a range of psychotherapies and some, mainly adjunctive, pharmacological interventions. However, around 20-30% of people fail to respond to the best available treatments and develop a persistent treatment-refractory illness. Novel treatments for these disorders are emerging, but their efficacy and clinical relevance need further investigation. In this review article, we first outline the evidence-base for the established treatments of the three 'classical' EDs [anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED)]. We then review research on some of the most promising emerging treatment modalities, discussing the questions and challenges that remain.
Lipodystrophy includes a wide group of diseases characterized by reduction, absence, or altered distribution of adipose tissue. Lipodystrophies are classified into generalized or partial, according to the fat distribution, and congenital or acquired, considering the etiology. Impaired glucose and lipid metabolism are typically present, thus severe insulin resistance, diabetes mellitus, dyslipidemia, and hepatic steatosis are frequent complications. Because of the rarity and the diversification of lipodystrophies, diagnosis might be challenging, typically for partial forms that cannot be easily recognized, leading to progression of the several metabolic abnormalities associated. First management of lipodystrophy is diet and lifestyle changes, followed by the treatment of metabolic complications. Replacement therapy with metreleptin, currently available in the USA and Europe, has shown improvement of metabolic profile in a great number of patients with lipodystrophy. The purpose of this review was to describe the phenotypic characteristics of all the known lipodystrophic types and to present specific steps for obtaining an early diagnosis and assessing the best treatment of lipodystrophy.
Berardinelli-Seip syndrome, also known as congenital generalized lipodystrophy (CGL), is a rare genetic disorder characterized by lipoatrophy, acromegaloid features, hyperinsulinemia, hypertriglyceridemia, and hepatic steatosis. With estimated prevalence 1 in every 10,000,000 births, CGL challenges medical specialists to seek better ways for early diagnosis of the disease. Despite its rarity, the condition is associated with severe metabolic and cardiovascular complications, leading to significant morbidity and reduced life expectancy. Advances in molecular genetics have identified mutations in AGPAT2, BSCL2, CAV1, and PTRF, which provide important insights into adipose tissue biology and systemic metabolism. Early recognition and genetic confirmation are crucial to initiate timely interventions, including lifestyle modification, insulin sensitizers, and lipid-lowering therapies including metreleptin therapy in indicated cases. Two illustrative cases are presented, reflecting our experience with the clinical variability, genetic findings, and therapeutic strategies in CGL as well as highlighting the importance of comprehensive care and emerging therapies.
Biallelic pathogenic leptin gene variants cause severe early-onset obesity usually associated with low or undetectable circulating leptin levels. Recently, variants have been described resulting in secreted mutant forms of the hormone leptin with either biologically inactive or antagonistic properties. We conducted a systematic literature research supplemented by unpublished data from patients at our center as well as new in vitro analyses to provide a systematic classification of congenital leptin deficiency based on the molecular and functional characteristics of the underlying leptin variants and investigated the correlation of disease subtype with severity of the clinical phenotype. A total of 28 distinct homozygous leptin variants were identified in 148 patients. The identified variants can be divided into 3 different subtypes of congenital leptin deficiency: classical hormone deficiency (21 variants in 128 patients), biologically inactive hormone (3 variants in 12 patients), and antagonistic hormone (3 variants in 7 patients). Only 1 variant (n = 1 patient) remained unclassified. Patients with biological inactive leptin have a higher percentage of 95th body mass index percentile compared to patients with classical hormone deficiency. While patients with both classical hormone deficiency and biological inactive hormone can be treated with the same starting dose of metreleptin, patients with antagonistic hormone need a variant-tailored treatment approach to overcome the antagonistic properties of the variant leptin. Categorization of leptin variants based on molecular and functional characteristics helps to determine the most adequate approach to treatment of patients with congenital leptin deficiency.