What is Microdosing on GLP-1?
Microdosing GLP-1 refers to the administration of small, sub-therapeutic doses of Glucagon-like peptide-1 (GLP-1), a hormone that regulates glucose levels in the body. This method is often used in scientific research and has potential benefits in managing diabetes and obesity by improving glucose control and promoting weight loss.
To understand what micro dosing GLP-1 means, we first need to understand what GLP-1 is and what it does when administered exogenously. Then, we can dive into what micro dosing GLP-1 entails and whether it has any benefits, particularly for blood sugar and weight management.
What is GLP-1?
Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone that plays a crucial role in glucose metabolism and overall energy homeostasis. It is secreted by L cells in the intestine and pancreatic alpha cells in response to nutrient ingestion [1]. This means that when you take in food, your L cells release GLP-1.
GLP-1 is an incretin, a type of hormone that stimulates insulin secretion, especially after meals, thereby helping regulate blood sugar levels [2]. It also inhibits glucagon secretion, delays gastric emptying, and increases satiety. These changes act together to reduce appetite [1].
GLP-1 has these effects by binding to specific GLP-1 receptors. GLP-1 receptors are also found on beta cells in the pancreas. When activated, this receptor stimulates insulin release in a glucose-dependent manner. This means that the more glucose there is in the blood, the more insulin will be produced to counterbalance the rise in glucose. GLP-1 receptor activation also increases β-cell mass, making them better at producing insulin - an ideal feature for the pharmacological management of type 2 diabetes [3].
However, the therapeutic utility of the native GLP-1 molecule is limited due to its rapid enzymatic degradation by a serine protease termed dipeptidyl peptidase-IV (DPP-IV) [4]. This is why many diabetes and weight loss drugs activate the GLP-1 receptor via alternative biological pathways, such as the glucagon-like peptide 1 receptor agonists developed by Novo Nordisk - Ozempic and Wegovy.
Can you take GLP-1?
Although GLP-1 has poor biological availability and a short half-life, you can still take GLP-1.
This is usually as a treatment for type 2 diabetes or comorbidity associated with obesity, including cardiovascular risk factors, joint health, and metabolic syndrome [5, 6].
How can we overcome GLP-1's short half-life and degradation in the body and enhance its therapeutic effects? Several approaches have been proposed, including continuous parenteral administration of the peptide via infusion pumps, inhibition of its in vivo degradation, and generation or use of modified derivatives/analogs of GLP-1 displaying prolonged biological activity [5].
GLP-1-based therapies, such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase 4, an enzyme that degrades endogenous GLP-1, have shown promising results in clinical trials [7].
However, it's important to note that while GLP-1 can be taken as a treatment, it should be under the supervision of a healthcare provider. As with any medication, there can be side effects, and discussing these with your doctor before starting treatment is crucial.
Benefits of Microdosing GLP-1
Microdosing GLP-1 involves administering small, controlled amounts of this hormone to manage blood glucose levels. This is a critical development in administering GLP-1, as natural GLP-1 breaks down quickly. This means that it would only stimulate insulin production and stabilize glucose for a couple of hours after injection. Microdosing is an effective way to ensure that the GLP-1 receptors are consistently stimulated glucose-dependent.
Microdosing can take many forms. Since 2008, researchers have been studying how to encapsulate GLP-1 into microspheres—microscopic synthetic vesicles that house the GLP-1 molecules and slowly release them over time [8]. More recent developments have focused on hydrogels, a different means of injecting GLP-1 into the body and releasing it over time [9].
Gene therapy is another promising method for microdosing GLP-1. This involves the delivery of GLP-1 genes into the body, enabling the production of GLP-1 and thus helping to manage blood glucose levels [10, 11].
The benefits of microdosing GLP-1 over taking sparser large doses are significant, particularly for individuals with type 2 diabetes. Microdosing GLP-1 can improve blood glucose control, protect β-cells, and stimulate insulin secretion [12]. It can also reduce food consumption, improving weight management [13]. Furthermore, continuous infusion of GLP-1 can significantly reduce diurnal glucose concentrations, reducing glucose levels, particularly at night, when low glucose levels are more desirable than during the day. Together, abundant evidence suggests that microdosing GLP-1 is a better option than single large doses of GLP-1 [14].
However, the efficacy of glucose and weight management of microdosing GLP-1 has not been directly compared to long-lasting GLP-1 agonists like Ozempic and Wegovy. Therefore microdosing GLP-1 may not be superior to these pharmaceutical products.