Microdosing GLP-1: Could It Be More Than Just a Weight-Loss Drug?

Weight loss drugs have been spotlighted in the media over the last several years—glorified, vilified, and everything in between. While criticism around this class of drugs lies in them being used like a silver bullet, inevitably turning into a silver pacifier, some doctors are honing in on the multifaceted effects of GLP-1 drugs on the body. 

What Is GLP-1 vs. GLP-1R Agonists?

GLP-1 (glucagon-like peptide-1) is a hormone that naturally occurs in the body, which helps regulate blood sugar by lowering the amount of glucose circulating in the blood, digestion, and appetite. GLP-1 receptor agonists (abbreviated GLP-1R agonists), on the other hand, are the synthetic versions that mimic the effects of GLP-1. They are prescribed as medications (like the brand name Ozempic) to treat type 2 diabetes and help with weight loss and are often abbreviated and referred to by laypersons as GLP-1 drugs.

Microdosing GLP-1 Drugs: The Pros and Cons

Doctors have already been exploring how adjusting the dose of GLP-1 drugs can curb side effects and expand use for treatment; as a weight-loss drug, anecdotal reports have claimed that a smaller dose curbs less undesirable side effects and lowers costs (Mammoser, 2024). However, to effectively microdose, patients would be using compounded versions of the drug, not prefilled pens, which is a measured dose (i.e., how name-brand drugs are administered).

Compounded versions are not FDA-approved and require the patient to measure the dose and administer it themselves. While a patient can be coached in this process by a licensed healthcare professional, there is still more room for error and thus risk: mis-measurements, adverse reactions, potential overdoses, and other complications (Mammoser, 2024).

Overall studies on GLP-1 drug microdosing are still lacking, and there is not substantial evidence to support the efficacy and safety of prescribing GLP-1R agonists for treatments beyond weight loss and diabetes. The studies that are emerging, however, do suggest that GLP-1 drugs’ effects are multi-systemic and could prove promising to manage other conditions. 

How the Dose Could Make the Multi-Use Medicine

Beyond weight loss and insulin management for those with diabetes, prescribing microdoses of GLP-1 drugs has arisen in part due to the drugs promising multifaceted effects on blood lipid control, blood pressure, insulin resistance, and some inflammatory conditions, such as arthritis. 

Blood Lipid Control

One study that set out to investigate the effects of GLP-1R agonists on the lipid profiles of patients with type 2 diabetes showed that they positively affect lipid profiles, including reductions in LDL cholesterol, triglycerides, and total cholesterol (Chae et al., 2024).

As dyslipidemia (a condition characterized by having more fat in the blood) and cardiovascular disease are common co-morbidities of those with diabetes, another recent finding reported that several trials looking at GLP-1R agonists have shown the drug to be safe and potentially helpful in positively affecting cardiovascular outcomes, therefore lowering the risk of cardiovascular disease (Berberich & Hegele, 2021).

Interestingly enough, the “plaque stabilization” effect exerted by GLP-1RAs resembles the pleiotropic effects of statins, which were approved a long time ago as first-line therapy to lower blood cholesterol levels”(Lecis et al., 2023). Such a similarity suggests GLP-1RAs mimic the effects of statins, and therefore have the potential to replace them.

Blood Pressure

For patients with diabetes, GLP-1R agonists have demonstrated a modest blood pressure-lowering effect, particularly for systolic blood pressure (Rivera et al., 2024). This effect may be due to increased natriuresis (the process by which the kidneys remove sodium from the body through urine), among inhibiting other functions of the renin-angiotensin-aldosterone system (a hormonal system that regulates blood pressure, fluid and electrolyte balance, and vascular resistance).

Insulin Resistance

One study published in the journal Diabetes demonstrated that GLP-1R agonists can help improve insulin sensitivity. Specifically, the GLP-1R agonist liraglutide—and therefore potentially other GLP-1 receptor agonists—was shown to rapidly improve insulin sensitivity, independent from weight loss (Mashayekhi et al., 2023). Because the effect on insulin was independent of weight loss, it shows promise to help in managing or even preventing type 2 diabetes. 

Inflammatory Conditions Like Arthritis

Since GLP-1R analogs have demonstrated potential anti-inflammatory effects, they may be beneficial for certain forms of arthritis and other inflammatory conditions, as suggested by numerous studies evaluated in a scoping review (Karacabeyli & Lacaille, 2024). These anti-inflammatory effects appear to be weight-independent and may involve inhibition of what is considered to be a prototypical proinflammatory signaling pathway called the NF-κB pathway.

GLP-1R Agonist Studies: Inconclusive, Promising, and Thought-Provoking

As most of these studies around GLP-1R agonists stem from looking solely at individuals with diseases and conditions that GLP-1 drugs are already used to treat, it’s inconclusive whether or not using these drugs with an isolated goal in mind—such as controlling blood-lipid levels or blood pressure, helping with insulin resistance, and treating other inflammatory conditions like arthritis—would be beneficial, as the drugs have a multi-systemic effect. Therefore, their use by otherwise healthy and metabolically stable individuals may not be appropriate and could have adverse effects. Only time and the science will tell. 

What do you think of these drugs’ use and the studies being done around microdosing GLP-1?

References

Berberich, A. J., & Hegele, R. A. (2021). Lipid effects of glucagon-like peptide 1 receptor analogs. Current opinion in lipidology, 32(3), 191–199. https://doi.org/10.1097/MOL.0000000000000750.

Chae, Y., Kwon, S. H., Nam, J. H., Kang, E., Im, J., Kim, H. J., & Lee, E. K. (2024). Lipid profile changes induced by glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a systematic review and network meta-analysis. Expert review of clinical pharmacology, 17(8), 721–729. https://doi.org/10.1080/17512433.2024.2363838.

Karacabeyli, D., & Lacaille, D. (2024). Glucagon-Like Peptide 1 Receptor Agonists in Patients With Inflammatory Arthritis or Psoriasis: A Scoping Review. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 30(1), 26–31. https://doi.org/10.1097/RHU.0000000000001949.

Lecis, D., Prandi, F. R., Barone, L., Belli, M., Sergi, D., Longo, S., Muscoli, S., Romeo, F., Federici, M., Lerakis, S., & Barillà, F. (2023). Beyond the Cardiovascular Effects of Glucagon-like Peptide-1 Receptor Agonists: Body Slimming and Plaque Stabilization. Are New Statins Born?. Biomolecules, 13(12), 1695. https://doi.org/10.3390/biom13121695.

Mammoser, G. (2024, October 17). Ozempic Microdosing: Benefits, Risks, and Effectiveness. Healthline. https://www.healthline.com/health-news/ozempic-microdosing-weight-loss#Ozempic-microdoing-what-is-it. 

Mashayekhi, M., Nian, H., Mayfield, D., Devin, J. K., Gamboa, J. L., Yu, C., Silver, H. J., Niswender, K., Luther, J. M., & Brown, N. J. (2023). Weight Loss–Independent Effect of Liraglutide on Insulin Sensitivity in Individuals With Obesity and Prediabetes. Diabetes, 73(1), 38–50. https://doi.org/10.2337/db23-0356.

Rivera, F. B., Lumbang, G. N. O., Gaid, D. R. M., Cruz, L. L. A., Magalong, J. V., Bantayan, N. R. B., Lara-Breitinger, K. M., Gulati, M., & Bakris, G. (2024). Glucagon-like peptide-1 receptor agonists modestly reduced blood pressure among patients with and without diabetes mellitus: A meta-analysis and meta-regression. Diabetes, obesity & metabolism, 26(6), 2209–2228. https://doi.org/10.1111/dom.15529.

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