What are the effects of micro-dosing Glucagon-like peptide-1 (GLP-1)?

From the Guidelines

Micro-dosing of GLP-1 receptor agonists is not recommended due to the lack of clinical evidence supporting its efficacy and safety, and it may compromise treatment outcomes. The most recent and highest quality study, published in JAMA in 2023 1, highlights the importance of using FDA-approved doses of GLP-1 receptor agonists, such as semaglutide and liraglutide, for obesity management in adults. These medications have been shown to be effective in reducing weight and improving weight-related comorbidities, as well as decreasing the risk of cardiovascular events, when used at the recommended doses.

The study found that subcutaneous semaglutide, dosed once weekly, resulted in a mean weight loss of 14.9% and 16.0% at 68 weeks, compared to 2.4% and 5.7% with placebo, in the STEP 1 and STEP 3 trials, respectively 1. Additionally, the SELECT study showed that semaglutide reduced the composite incidence of death due to cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke at 39.8 months, with a hazard ratio of 0.80 (95% CI, 0.72-0.90) 1. These findings suggest that using the recommended doses of GLP-1 receptor agonists is crucial for achieving optimal therapeutic benefits.

Some key points to consider when using GLP-1 receptor agonists include:

• Starting with the lowest approved dose and gradually titrating upward according to the medication's prescribing information
• Using the recommended doses to achieve adequate blood levels and properly activate GLP-1 receptors
• Working with a healthcare provider to monitor side effects and adjust the dose as needed
• Avoiding unsupervised micro-dosing, which lacks clinical evidence and may compromise treatment outcomes

Overall, the evidence suggests that using GLP-1 receptor agonists at the recommended doses is essential for achieving optimal therapeutic benefits and minimizing potential side effects. Therefore, micro-dosing of GLP-1 receptor agonists is not recommended, and patients should work with their healthcare provider to use these medications safely and effectively.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Micro-dosing of GLP-1

• Micro-dosing of GLP-1 is not explicitly mentioned in the provided studies, however, the studies discuss the various dosing regimens of GLP-1 receptor agonists (GLP-1 RAs) 2, 3, 4, 5, 6.
• The dosing regimens of GLP-1 RAs vary, with some administered twice daily (exenatide b.i.d.), once daily (lixisenatide and liraglutide), or once weekly (exenatide once weekly, dulaglutide, albiglutide, and semaglutide) 2.
• A daily oral preparation of semaglutide has also been approved, which has demonstrated clinical effectiveness close to the once-weekly subcutaneous preparation 2.
• The studies suggest that the choice of GLP-1 RA and dosing regimen depends on individual patient factors, such as patient preferences, potential adverse effects, and cost 3, 6.

GLP-1 Receptor Agonists

• GLP-1 RAs have been shown to be effective in reducing HbA1c, improving fasting plasma glucose, inducing weight loss, and reducing appetite 2, 3, 4, 5, 6.
• The mechanisms of action of GLP-1 RAs include augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion, deceleration of gastric emptying, and reduction in calorie intake and body weight 2, 6.
• GLP-1 RAs have also been shown to have cardioprotective effects, with some studies suggesting that they can prevent cardiovascular events such as acute myocardial infarction or stroke and associated mortality 2, 4.

Clinical Implications

• The studies suggest that GLP-1 RAs are a valuable treatment option for patients with type 2 diabetes, particularly those who have not achieved adequate glycemic control with other therapies 2, 3, 6.
• GLP-1 RAs may also be beneficial for patients with type 1 diabetes, with one study showing that liraglutide can improve glycemic control and reduce insulin dose in patients with long-standing type 1 diabetes 5.
• However, the studies also note that GLP-1 RAs can be associated with gastrointestinal side effects, such as nausea, and may increase the risk of hypoglycemia when used in combination with insulin or insulin secretagogues 3, 4, 5.