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by Jennifer Lines, PharmD Candidate, PCCA Clinical Services Intern, and Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized metabolic health and weight management, leading to a host of new weight loss wonder drugs. But did you know that recent evidence shows these new drugs may do more than just help with weight loss and diabetes? And at a fraction of the standard dose?
Originally discovered in the saliva of the Gila monster, exenatide — a GLP-1 RA— was approved as a twice-daily injection by the FDA in 2005 for adults with type 2 diabetes.1 Within the past decade, longer-acting GLP-1 RA formulations entered the market as once-weekly, self-administered injectable pens — most notably, semaglutide.
Recent FDA approvals and indications for products containing semaglutide include the reduction of cardiovascular risk in patients with type 2 diabetes and body weight reduction for obesity. New research, however, reveals the potential for additional benefits of the drugs.
Known for their metabolic benefits, emerging studies suggest GLP-1 RAs may help improve kidney function, cardiovascular health, non-alcoholic fatty liver disease, Alzheimer's disease and Parkinson’s disease.2
GLP-1 RAs, such as semaglutide, also show potential anti-inflammatory properties. Although the specific mechanisms are not understood, reports indicate that semaglutide can modulate inflammatory processes by reducing levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hsCRP).
In an animal model, semaglutide demonstrated neuroprotective effects and improved cognitive function by inhibiting the release of inflammatory cytokines mediated by the NLRP3 inflammasome, a protein involved in regulating the innate immune system and inflammatory responses.
GLP-1 receptors are also found on different immune cells, such as neutrophils and eosinophils, and their activation has modulatory effects on immune responses and inflammatory processes associated with these types of cells.3
Microdosing is not an official medical term; it refers to taking less than the standard dose of a medication to achieve benefits while potentially minimizing undesirable side effects.
The term microdosing has risen in popularity in recent years. Initially, it referred to taking small doses of psychedelic drugs to alleviate symptoms of depression and anxiety, or boost mood and creativity. Interest in microdosing GLP-1 RAs is growing among many holistic physicians.4
At normal physiological levels, active GLP-1 levels peak around 30-60 minutes after ingesting a meal before being rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). During DPP-4 inhibition, levels of active GLP-1 increase up to 2-3 times. However, with exogenous GLP-1 RAs, active levels of GLP-1 RAs can rise to 10-30 times the normal physiological levels (depending on the agent used) and maintain steadily high levels independent of meal ingestion. One of the most common reasons patients discontinue GLP-1 RA treatment is due to gastrointestinal side effects, which could be attributed to the markedly high GLP-1 RA levels.5
Anecdotal discussions between holistic practitioners suggest microdosing semaglutide may help people lose weight while limiting side effects. Naturopathic physician Dr. Tyna Moore, for example, suggests people with reduced GLP-1 levels may benefit from lower dosing and slowly increasing to the patient’s normal physiological levels. Dr. Moore also believes that slower, more sustainable weight loss allows the body more time to adjust to changes in weight, reducing the side-effect profile and potentially leading to better long-term success.6
While there are no clinical studies exploring the concept of microdosing GLP-1 RAs, it may be a useful tool for a holistic metabolic health strategy. It is important to remember that GLP-1 RAs are only one piece of the puzzle and should always be recommended in conjunction with diet, exercise and lifestyle modifications.
Smaller doses of GLP-1 RAs may not benefit those with severe metabolic dysfunction or those needing substantial weight loss. However, it may be helpful to those seeking a more gradual approach to weight loss while potentially providing overall health benefits like anti-inflammatory and neuroprotective effects.
While the safety of GLP-1 RAs is well established, current scientific evidence on the efficacy of microdosing GLP-1 RAs is lacking and further research is required to assess its benefits at lower doses.7
PCCA members with clinical services access may contact our Clinical Services team for help with microdosing GLP-1 RAs and other compounding concerns.
These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.