Do Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) reduce the development of diabetes?

From the Guidelines

GLP-1 receptor agonists (GLP-1 RAs) have been shown to reduce the risk of developing type 2 diabetes in high-risk individuals, as evidenced by the most recent and highest quality study available 1. The use of GLP-1 RAs, such as semaglutide, liraglutide, and dulaglutide, has been associated with a reduced risk of major adverse cardiovascular events (MACE) and chronic kidney disease (CKD) progression in patients with type 2 diabetes 1. Some key points to consider when using GLP-1 RAs for diabetes prevention include:

• The medications work by mimicking the incretin hormone GLP-1, which stimulates insulin secretion, suppresses glucagon release, slows gastric emptying, and reduces appetite 1.
• The weight loss effect of GLP-1 RAs is particularly important, as losing 5-10% of body weight significantly reduces diabetes risk 1.
• GLP-1 RAs may cause side effects like nausea, vomiting, and diarrhea, especially when starting treatment, but these symptoms are usually tolerable with dose titration and abate over several weeks to months 1.
• The most recent and highest quality study available 1 suggests that GLP-1 RAs, along with SGLT2 inhibitors, reduce all-cause mortality and MACE compared with usual care in adults with type 2 diabetes. It is essential to note that while GLP-1 RAs have shown promise in reducing the risk of developing type 2 diabetes, they are primarily approved for treating existing diabetes or obesity, and their preventive benefits are increasingly recognized 1. In clinical practice, the decision to use GLP-1 RAs for diabetes prevention should be made on a case-by-case basis, taking into account the individual patient's risk factors, medical history, and potential benefits and harms of treatment 1.

From the Research

GLP-1 Receptor Agonists and Diabetes Development

• The provided studies do not directly address whether GLP-1 receptor agonists (RAs) reduce the development of diabetes, but rather focus on their use in the treatment of existing type 2 diabetes 2, 3, 4, 5, 6.
• GLP-1 RAs have been shown to be effective in improving glycemic control, promoting weight loss, and reducing the risk of major cardiovascular outcomes in patients with type 2 diabetes 2, 3, 4, 5, 6.
• The mechanisms of action of GLP-1 RAs, including augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion, and deceleration of gastric emptying, may contribute to their potential benefits in reducing the development of diabetes, but this is not explicitly stated in the provided studies 2, 3, 4, 5, 6.

Differences Between GLP-1 RAs

• The studies highlight the differences between short-acting and long-acting GLP-1 RAs, with long-acting agents affecting both fasting glucose and postprandial glucose, and short-acting agents primarily delaying gastric emptying 5.
• The choice of GLP-1 RA may depend on individual patient needs and preferences, with considerations including dosing frequency, administration requirements, and cost 6.

Clinical Evidence

• Head-to-head clinical studies have demonstrated that all GLP-1 RA agents are effective therapeutic options for reducing A1C, but differences exist in terms of magnitude of effect on A1C and weight as well as frequency of adverse effects 6.
• GLP-1 RAs have been shown to have a low risk of hypoglycemia and may also have cardiovascular benefits, making them an attractive option for the treatment of type 2 diabetes 2, 3, 4, 5, 6.