Obesity pharmacotherapy has had a difficult history, with many challenges, and some effective medicines withdrawn due to safety concerns. More recently, better understanding of the biological mechanisms underlying body weight regulation have led to development of more effective treatments, some of which are now entering clinical use. These include treatments for single gene disorders, such as metreleptin for the rare condition of leptin deficiency, and setmelanotide for pro-opiomelanocortin (POMC) deficiency, leptin receptor mutations and some melanocortin 4 receptor mutations. One of the most promising areas relates to hormones from the GI tract that have physiological roles in satiety, such as glucagon like peptide 1 (GLP1), peptide YY and amylin; the only approved treatment in this class is liraglutide 3mg, given sc daily, which has recently been approved by NICE for a limited group of patients with severe obesity and impaired glucose regulation. More recently we have seen the results of studies with the weekly injectable GLP1 RA semaglutide that results in weight loss of 15% or more and is associated with improvements in cardiovascular risk factors and quality of life; a major cardiovascular outcome trial, SELECT, is underway in people with obesity without diabetes who have a history of cardiovascular disease. Combining different gut hormones may give even greater weight loss. Promising data are emerging with tirzepatide, a GLP-1/GIP receptor agonist, that has shown weight loss in excess of 10% in people with diabetes. The combination of semaglutide with an analogue of the islet hormone amylin (cagrilintide), has shown weight loss of 17% over 20 weeks in a phase 2A trial. Thus in the future we may see medication that results in weight loss sufficient to rival the effects of bariatric surgery.
30 Jun 2021 - 01 Jul 2021