Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists

Obesity is a chronic disease associated with many complications. Weight loss of 5–15% can improve many obesity-related complications. Despite the benefits of weight reduction, there are many challenges in losing weight and maintaining long-term weight loss. Pharmacotherapy can help people with obesity achieve and maintain their target weight loss, thereby reducing the risk of obesity-related complications. The prevalence of obesity in the USA has been increasing over the past few decades, and despite the availability of approved anti-obesity medications (AOMs), people with obesity may not be accessing or receiving treatment at levels consistent with the disease prevalence. Reasons for low levels of initiation and long-term use of AOMs may include reluctance of public health and medical organizations to recognize obesity as a disease, lack of reimbursement, provider inexperience, and misperceptions about the efficacy and safety of available treatments. This article aims to inform primary care providers about the mechanism of action of one class of AOMs, glucagon-like peptide 1 receptor agonists (GLP-1RAs), in weight loss and longer-term maintenance of weight loss, and the efficacy and safety of this treatment class. GLP-1RA therapy was initially developed to treat type 2 diabetes. Owing to their effectiveness in reducing body weight, once-daily subcutaneous administration of liraglutide 3.0 mg has been approved, and once-weekly subcutaneous administration of semaglutide 2.4 mg is being investigated in phase III trials, for obesity management. Considerations regarding adverse effects and contraindications for different drug classes are provided to help guide treatment decision-making when considering pharmacotherapy for weight management in patients with obesity. Obesity is a growing public health issue that increases the risk of developing heart disease, type 2 diabetes, and osteoarthritis. Weight loss can reduce the risk of developing these health problems but, despite this, levels of obesity remain high. Achieving and maintaining weight loss is challenging for many individuals. There is therefore a need for some patients to take medications to help them lose weight and prevent weight regain. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are a type of medication originally developed to treat type 2 diabetes, but are now being used for the treatment of obesity because they are effective at helping people to lose weight. One GLP-1RA, liraglutide, has been approved to treat obesity, and another, semaglutide, is in clinical trials. GLP-1RAs work by reducing the appetite and feelings of hunger, slowing the release of food from the stomach, and increasing feelings of fullness after eating. Most people can tolerate GLP-1RAs well. The most common side effects (nausea, vomiting, and diarrhea) are usually mild and occur in the first few weeks of treatment, reducing over time. Because of the difficulties many people face in maintaining weight loss, lifelong treatment may be needed. In clinical trials, GLP-1RAs were well tolerated and effective at helping people prevent weight regain, and may be a good option for long-term weight control and lowering patients’ chances of serious health problems.