Is microdosing Glucagon-like peptide-1 (GLP-1) analogs, such as liraglutide (Victoza or Saxenda) or semaglutide (Ozempic or Wegovy), safe for diabetes management or weight loss?

From the Guidelines

Microdosing GLP-1 analogs like liraglutide (Victoza/Saxenda) or semaglutide (Ozempic/Wegovy) is not recommended for diabetes management or weight loss. These medications require specific, FDA-approved dosing regimens that typically involve gradual dose escalation to reach therapeutic levels, as recommended by the AGA clinical practice guideline on pharmacological interventions for adults with obesity 1. For example, semaglutide treatment starts at 0.25mg weekly, increasing over time to 1-2mg weekly for Ozempic or 2.4mg weekly for Wegovy. Taking smaller, unauthorized doses ("microdosing") may not provide clinical benefits while still exposing patients to potential side effects. GLP-1 analogs work by enhancing insulin secretion, reducing glucagon release, slowing gastric emptying, and affecting appetite centers in the brain - mechanisms that require adequate drug concentrations to be effective.

Some key considerations when using GLP-1 receptor agonists include:

• Gradual dose titration to minimize risk of GI adverse effects
• Starting with a low dose and gradually increasing to the maintenance dose
• Clinical judgment is recommended for adjusting the titration schedule as needed for an individual patient’s response, tolerance, and adverse effects
• If more than 2 consecutive doses are missed, clinical judgment is required to decide on subsequent dosing, and restarting the titration schedule should be considered if 3 or more consecutive doses are missed 1.

Additionally, GLP-1 RAs have been associated with thyroid C-cell tumors in rodents in a dose- and treatment duration-dependent fashion, and caution is advised when using GLP-1 RAs in combination with insulin or insulin secretagogues (eg, sulfonylureas) 1. These medications should only be used under medical supervision with proper prescription dosing to ensure safety and efficacy. If considering GLP-1 therapy, consult with a healthcare provider who can determine appropriate dosing based on your specific health needs.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Microdosing GLP-1 for Diabetes Management and Weight Loss

• Microdosing GLP-1 analogs, such as liraglutide and semaglutide, has been studied for its safety and efficacy in diabetes management and weight loss 2, 3, 4, 5, 6.
• Liraglutide, a GLP-1 receptor agonist, has been shown to effectively control hyperglycemia and assist patients in meeting established glycemic targets, with a lower risk of hypoglycemia compared to other antidiabetic agents 2.
• Semaglutide, another GLP-1 receptor agonist, has been proven to be safe in adults and elderly patients with renal or hepatic disorders, with no dose modification required, and has been shown to reduce various cardiovascular risk factors in patients with established cardiovascular disorders 3.
• Oral semaglutide, the first oral GLP-1 receptor agonist, has been studied in the PIONEER trials, demonstrating similar efficacy to subcutaneous GLP-1 receptor agonists in terms of HbA1c lowering and weight loss 4.
• The discovery of semaglutide, a once-weekly GLP-1 analogue, has been reported, with a prolonged exposure and action compared to liraglutide 5.
• GLP-1 agonists, including semaglutide and liraglutide, have been associated with improved long-term outcomes, but also with adverse events such as gastrointestinal adverse events, pancreatitis, and biliary disease 6.

Safety and Efficacy

• The safety and efficacy of microdosing GLP-1 analogs have been evaluated in several studies, with results indicating that these agents can be effective in controlling hyperglycemia and promoting weight loss, with a relatively low risk of hypoglycemia 2, 3, 4.
• However, GLP-1 agonists have also been associated with adverse events, and patients should be closely monitored for potential complications, such as gastrointestinal adverse events and pancreatitis 6.

Clinical Use

• GLP-1 agonists, including semaglutide and liraglutide, are currently in use for the treatment of diabetes and obesity, and emergency clinicians should be aware of the potential complications associated with their use 6.
• The American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) have cited the efficacy and low risk of hypoglycemia of GLP-1 agonists, preferring them over sulfonylureas and glinides, after initial treatment with metformin 2.