Good to know: GLP-1 and dual incretin-based medications

It's hard to miss the surge of incretin-based therapies lining pharmacy shelves. Esatto has simplified GLP-1 education with a guide designed to increase awareness and improve understanding of the GLP-1-based and dual incretin class of medications.

What is "GLP-1"?

The term "GLP-1" is used in popular conversation to refer to a category of incretin-based medications. These therapies are modeled after the naturally occurring incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

The GLP-1 and GIP hormones are chemical messengers that travel throughout the body, binding to specialized cell receptors that were built to receive them. This binding action triggers the receptor to respond, igniting a cascade of biochemical reactions.

GLP-1 receptor agonists (GLP-1 RAs), like semaglutide, are medications that activate the GLP-1 receptor. Tirzepatide belongs to a related but distinct category known as a dual GIP/GLP-1 receptor agonist (GIP/GLP-1 RA) because it activates both GIP and GLP-1 receptors.

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The research evolution

Research into GLP-1 has been ongoing for decades, long before they became widely recognized, with researchers globally studying the hormone to better understand its nature and impact on healthcare.

The discovery of insulin in the 1920s prompted scientists to investigate the regulation of insulin secretion, the process by which insulin is released into the bloodstream. By the 1980s, researchers had identified GLP-1 as a key incretin hormone, paving the way for continued research into incretin biology and the development of therapies that target GLP-1 and GIP signaling pathways.

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How incretin-based medications work

GLP-1 RAs and dual GIP/GLP-1 RAs work through multiple mechanisms of action that influence glucose regulation, appetite, digestion, and energy balance, including:

01 Regulating insulin and blood glucose levels

When the medication binds to receptors on a target cell, the cell is activated and begins producing and releasing insulin. Simultaneously, the medication prevents the release of glucose. When insulin signaling and blood glucose regulation are functioning properly, the body can efficiently burn fat and glucose for "fuel" instead of storing them.

02 Slowing digestion and improving blood sugar control

When food is digested too quickly, it can cause sharp spikes in blood sugar, leading to increased insulin and glucose levels. Sharp fluctuations in blood sugar can contribute to fatigue, hunger, and irritability. Slowing down your digestion can help prevent these sharp spikes.

GLP-1 medications slow digestion in two ways: by reducing the frequency of gut muscle contractions and by activating the vagus nerve, which in turn reduces stomach contractions.

03 Reducing appetite and increasing satiety

GLP-1 medications interact with receptors in the hypothalamus, a key region of the brain that regulates hunger and satiety. When the GLP-1 receptor agonist binds to target-cell receptors in the hypothalamus, the target cell activates neurons that signal fullness to the body and inhibits neurons that signal hunger.

04 GIP signaling

Dual GIP/GLP-1 RAs activate an additional incretin pathway through the GIP receptor.

Research suggests that activating both GIP and GLP-1 receptors may contribute to improvements in glucose regulation, energy balance, and weight management.

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The clinical impact

The World Health Organization (WHO) identifies obesity as a complex disease with serious health risks, estimating that ~890 million adults live with obesity globally, with ~2.5 billion adults overweight (WHO, 2022). GLP-1 RAs and dual GIP/GLP-1 RAs are recognized as evidence-based treatments that work to address obesity and weight from a molecular perspective, placing them at the front and center of metabolic conversations.

Beyond metabolism

Today, researchers have identified GLP-1 and GIP receptors throughout multiple organ systems, including the pancreas, brain, gastrointestinal tract, cardiovascular system, kidneys, and immune-related tissues.

This broad distribution helps explain why scientists continue to investigate GLP-1 signaling beyond its established role in blood sugar regulation. From metabolism and cardiovascular health to inflammation and neurological pathways, their findings reinforce an important principle: biological systems rarely operate in isolation.

Apply this concept to healthcare. Provider, patient, pharmacist - it can be a highly effective system, and it highlights the need for care approaches that account for the physiological complexities being discussed today.

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Compounded incretin-based therapies

To prepare compounded incretin-based medications, compounding pharmacies utilize active pharmaceutical ingredients (APIs) sourced from qualified suppliers and prepare formulations according to rules, regulations, and compounding standards.

While compounding pharmacies are authorized under the Federal FD&C Act and must follow strict U.S. Pharmacopeia and state regulations, quality standards can sometimes vary across the marketplace. To help ensure quality and safety, verify that your compounding pharmacy is state-licensed, follows USP standards, and sources pharmaceutical-grade ingredients from qualified suppliers.

Why compounding

Compounded medications offer the benefit of customizing dosage strength, formulation, and delivery method. This enables providers to tailor treatments to a patient's individual needs and goals.

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3 key takeaways

01 The science is sound

Although incretin-based therapies such as semaglutide and tirzepatide have only recently gained widespread attention, decades of research support the science behind these modern metabolic therapies. More recent research continues to demonstrate their clinical use and expand our understanding of incretin biology, paving the way for expanded treatment options.

02 Incretin-based medications work through multiple pathways

GLP-1 RAs and dual GIP/GLP-1 RAs are classes of incretin-based medications that work to mimic the activity of their naturally occurring counterparts. These medications help support long-term weight management through insulin and glucose regulation, slowed digestion, and appetite reduction.

03 Support from compounding pharmacies matters

Compounding pharmacies are state-licensed and adhere to state and U.S. Pharmacopeia regulations. These regulated pharmacies can customize the dosage, strength, formulation, and delivery method of GLP-1 RA and dual GIP/GLP-1 RA medications when prescribed by a licensed healthcare provider.

Read Esatto's FAQs section to learn more about compounding.

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