Opportunities to optimize lifestyle interventions in combination with glucagon‐like peptide‐1‐based therapy

Abstract

AbstractObesity is a chronic multi‐system disease and major driver of type 2 diabetes and cardiometabolic disease. Nutritional interventions form the cornerstone of obesity and type 2 diabetes management. Some interventions such as Mediterranean diet can reduce incident cardiovascular disease, probably independently of weight loss. Weight loss of 5% or greater can improve many adiposity‐related comorbidities. Although this can be achieved with lifestyle intervention, it is often difficult to sustain in the longer term due to adaptive endocrine changes. In recent years glucagon‐like‐peptide‐1 receptor agonists (GLP‐1RAs) have emerged as effective treatments for both type 2 diabetes and obesity. Newer GLP‐1RAs can achieve average weight loss of 15% or greater and improve cardiometabolic health. There is heterogeneity in the weight loss response to GLP‐1RAs, with a substantial number of patients unable to achieve 5% or greater weight. Weight loss, on average, is lower in older adults, male patients and people with type 2 diabetes. Mechanistic studies are needed to understand the aetiology of this variable response. Gastrointestinal side effects leading to medication discontinuation are a concern with GLP‐1RA treatment, based on real‐world data. With weight loss of 20% or higher with newer GLP‐1RAs, nutritional deficiency and sarcopenia are also potential concerns. Lifestyle interventions that may potentially mitigate the side effects of GLP‐1RA treatment and enhance weight loss are discussed here. The efficacy of such interventions awaits confirmation with well‐designed randomized controlled trials.