The role of GLP-1 receptor agonists as weight loss agents in patients with and without type 2 diabetes

Obesity contributes to the pathogenesis of type 2 diabetes (T2DM) and cardiovascular disease. A modest weight loss of 5-10% can have significant impact on glucose control, medications use and patients' functionality and quality of life. Until recently, only orlistat was approved in Europe for weight loss. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to improve glycaemia in patients with T2DM with an added benefit of weight reduction. However, the weight loss varies considerably within class and between individuals with up to 30% of patients not losing weight with GLP-1 RA treatment. GLP-1 RAs were placed as a possible second-line treatment as an add on to metformin by the latest ADA/EASD joint guidelines while NICE placed them as third-line agents for patients with T2DM and a body mass index (BMI) ≥35kg/m ² and inadequate glycaemic control. NICE recommended that GLP-1 RAs can be used in patients with BMI <35kg/m ² in ethnic groups, when used as an alternative to insulin where insulin treatment has vocational implications, or if weight loss would be beneficial for other medical reasons. A GLP-1 RA (Saxenda) has recently been approved by the FDA and EMA as a weight loss treatment in patients without T2DM. This paper aims to review the impact of GLP-1 RA treatment on weight loss in patients with and without diabetes, from clinical trials as well as real-life UK data from the ABCD nationwide audits, and also discuss the future role of GLP-1 RAs.