Médicaments anti-obésité : leçons des échecs pour l'avenir

Both physicians and patients dream of an efficacious and safe pharmacological approach to treat obesity. Unfortunately, most anti-obesity drugs prescribed since the fifties have been associated with an unfavourable risk profile that led to numerous withdrawals during the last 25 years. Medications from pharmaco-chemistry that mainly target brain amines to reduce appetite have been abandoned because of potential cardiovascular and neuropsychiatric toxicities. More recently, biological medications emerged, in particular the glucagon-like peptide-1 (GLP-1) receptor agonist alone, such as those already on the market (liraglutide, semaglutide) or as co-agonists, combined with agonists of receptors of glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon, currently in development. Whatever the drug considered, it must meet three main criteria: to support but not to replace life-style measures, to allow sufficient weight loss and to maintain this beneficial weight loss over the long term, and to be able to be administered as a safe and sustainable therapy, if obesity is considered to be a chronic disease. Because of the complexity of the pathophysiology of obesity, various combined therapies with complementary mechanisms of action would most probably be necessary to obtain a sufficient efficacy, as in type 2 diabetes and arterial hypertension. However, their tolerance and safety profile will still have to be acceptable! © 2021 Elsevier Masson SAS