Understanding Incretin: Function, Roles, and Types

May 19, 2025

Have you ever noticed how a satisfying meal feels fuller than a sugary snack? This experience is a result of your body's complex inner workings. At the heart of this process are incretins, powerful hormones produced in your gut that play a vital role in controlling appetite, blood sugar, and even weight.

This blog will explore what incretins are, explain their key roles and functions, and identify the main incretin hormones. You will also discover the potential of incretins in addressing metabolic disorders like diabetes and obesity.

So, let’s uncover their curious workings and understand their growing significance in modern healthcare!

What is incretin?

Incretins are a fascinating group of hormones, produced by specialised cells lining your gut in direct response to the food you eat. They function as the gut's early warning system, preparing the rest of your body for the incoming nutrients.

These messengers have various important tasks, functions, and roles, including:

Raising insulin levels after you eat: This helps your body move glucose from the bloodstream into your cells for energy or storage.
Slowing gastric emptying: By slowing down the rate at which food leaves your stomach, they promote a feeling of fullness and lead to a more gradual rise in blood sugar.
Promoting satiety: They send signals to your brain that help you feel satisfied and reduce further food intake.
Lowering stomach acid: This can affect digestion and nutrient absorption.
Suppressing glucagon secretion: Glucagon is a hormone that raises blood sugar, so suppressing it helps to maintain stable glucose levels after a meal.
Raising glucose storage in muscles: This helps to clear glucose from the bloodstream.
Regulating appetite and cravings: They play a role in the complex signals that control how hungry or full you feel.

Incretin effect

The incretin effect is a particularly interesting phenomenon related to incretins. When people consume glucose orally (through food or drink), they release significantly more insulin than when the same amount of glucose is administered directly into their bloodstream via an intravenous (IV) infusion.

This difference in insulin response highlights the crucial role of gut hormones like incretins. When glucose enters the gut, incretins are released, amplifying the insulin response in anticipation of the incoming nutrients. This incretin effect is a vital part of normal glucose regulation and nutrient management.

With that fascinating glimpse into the incretin effect, let's familiarise ourselves with the hormones driving this remarkable process.

The main incretin hormones

While the incretin family includes various members, two key players stand out for their significant roles in regulating blood glucose levels and influencing body weight: Glucagon-Like Peptide-1 (GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP).

GLP-1 (Glucagon-Like Peptide-1)

This incretin hormone is secreted by L-cells in the small and large intestine in response to nutrient intake. Its actions are multifaceted and contribute significantly to glucose homeostasis and weight management.

After you eat, your body's glucose landscape becomes a bustling place, where GLP-1 plays the conductor:

It encourages insulin secretion by binding to its receptor on pancreatic β cells, which then amplifies insulin production in a glucose-dependent manner.
It also suppresses glucagon, another hormone that raises glucose levels in the bloodstream.
GLP-1 slows down gastric emptying. This means food stays longer in the stomach, which can increase the feeling of fullness or satiety.

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GIP (Glucose-Dependent Insulinotropic Polypeptide)

Also known as gastric inhibitory peptide, GIP is another major incretin hormone released by K-cells primarily in the upper small intestine in response to glucose and fat ingestion. Its primary action includes:

Stimulating insulin release from the pancreas in a glucose-dependent manner.
It also has roles in fat metabolism and other bodily functions, although its precise impact on weight regulation is more complex and still under investigation.

These hormones are hard at work, but how exactly do they pull off these feats? Let's break it down!

How do incretin hormones work?

The magic of incretin hormones lies in their coordinated and multifaceted actions throughout the body, triggered by the simple act of eating. Let's take a closer look at how these remarkable messengers work:

Release mechanism: When you intake carbohydrates, fats, or proteins, L-cells in the lower small intestine release GLP-1 into the bloodstream. Simultaneously, K-cells in the upper part of the small intestine respond to the arrival of glucose and fats by secreting GIP.
Action on the pancreas: Once released, these hormones bind to specific receptors on the pancreatic beta cells, triggering a response that boosts insulin secretion in response to elevated glucose levels. This targeted approach minimises the risk of hypoglycemia.

GLP-1 simultaneously acts on pancreatic alpha cells to curb glucagon release, further assisting in maintaining glucose homeostasis.

Action on the stomach: GLP-1 acts on the stomach to slow down gastric emptying. This leads to a more gradual glucose absorption into the bloodstream and contributes to the feeling of satiety and fullness after a meal.
Action on the brain: GLP-1 binds to receptors in areas of the brain that regulate appetite, reducing hunger signals and increasing feelings of fullness. This central action plays a significant role in the potential of GLP-1-based therapies for weight management.
Other potential actions: Incretin hormones indirectly affect the liver by regulating insulin and glucagon release, resulting in a balanced glucose metabolism.

Also read: How to Naturally Increase GLP-1 Levels?

But what happens when this incretin magic isn’t enough? Let’s explore the world of incretin-based therapies next.

Therapeutic uses of incretin-based drugs

The incretin effect can be diminished or impaired in certain conditions, especially when the pancreas becomes less responsive to GIP and GLP-1 secretion may be reduced in type 2 diabetes. This diminished response contributes to the challenges of managing blood sugar effectively.

To address this, researchers have developed synthetic versions of these hormones, known as incretin mimetics, to restore or enhance the incretin effect. These medications have found a significant place in the treatment of type 2 diabetes and obesity.

Incretin mimetics can be categorised into the following:

GLP-1 receptor agonists: These drugs, as the name suggests, bind to and activate the GLP-1 receptor, mimicking the actions of GLP-1.
Drugs that enhance the effects of both GLP-1 and GIP: GIP receptor agonists, dual agonists (activate both GLP-1 and GIP receptors), and triple agonists.

Here's a table highlighting some key GLP-1 receptor agonists:

Generic name	Brand for type 2 diabetes	Brand for weight management	Directions of use
Dulaglutide	Trulicity	N/A	Injection (once a week)
Liraglutide	Victoza	Saxenda	Injection (once a day)
Semaglutide	Ozempic	Wegovy	Injection (once a week)
Semaglutide	Rybelsus	N/A	Pill (once a day)
Exenatide	Byetta	N/A	Injection (once a day)
Exenatide	Bydureon	N/A	Injection (once a week)

Incretin mimetics for weight loss and obesity

GLP-1 receptor agonists have shown promise in promoting weight loss through several mechanisms:

Slowing down food passing through the GI tract: GLP-1 agonists slow gastric emptying, leading to a feeling of fullness and reduced food intake.
Controlling your appetite: These medications act on appetite centers in the brain, helping to curb hunger and cravings.
Regulating hunger hormones: They can influence hormones like ghrelin (which stimulates hunger) and leptin (which signals satiety), which helps regulate appetite.

Clinical trials and real-world use have demonstrated significant weight loss with GLP-1 receptor agonists. An important study published in the New England Journal of Medicine found that 3.0 mg of liraglutide, as an adjunct to diet and exercise, resulted in at least 5% reduction in body weight.

Compared to some older weight loss medications, GLP-1 agonists offer advantages such as a potentially more favourable cardiovascular risk profile. However, if incretin mimetics don’t work for you, here are other medications to consider:

Qsymia: This is a combination medication containing phentermine and topiramate. It promotes weight loss by lowering your appetite and helping you feel full sooner.
Orlistat (Xenical, Alli): Orlistat works by blocking your intestines from absorbing fat from the food you eat.

Important note: Incretin mimetics are typically approved for weight loss in adults with a BMI of 30 kg/m² or higher, or a BMI of 27 kg/m² who also have a weight-related health condition such as Type 2 diabetes. The safety and effectiveness of these medications haven't been established for weight loss outside of these specific groups.

Also read: Do GLP-1 Supplements Work Naturally for Health?

Incretin mimetics for type 2 diabetes

GLP-1 receptor agonists are also valuable tools in managing type 2 diabetes:

They work by stimulating glucose-dependent insulin release, boosting insulin secretion when blood sugar is high, helping to lower it.
They also suppress glucagon secretion, further contributing to blood sugar control.
Additionally, there's evidence that they may potentially improve beta-cell function over time, which is crucial in type 2 diabetes.

A review of GLP-1 receptor agonists in type 2 diabetes found that these medications reduced HbA1c levels, a measure of long-term blood sugar control, by approximately 1%.

If incretin mimetics aren't suitable, other effective treatments for type 2 diabetes are available, including:

Metformin: Often the first-line medication for type 2 diabetes.
Insulin: Used when the body doesn't produce enough insulin.
DPP-4 inhibitors: These medications work by preventing the breakdown of natural incretins.
SGLT2 inhibitors: These drugs help the kidneys remove excess glucose from the body.

Before we wrap things up, here’s what you need to know about the safety of incretin mimetics.

Are incretin mimetics safe?

While generally considered safe and effective for many individuals with type 2 diabetes and obesity, it's important to be aware of the potential side effects associated with incretin mimetics.

Common side effects

These are the most frequently reported side effects and often tend to be mild to moderate. They may decrease over time as your body adjusts to the medication:

Nausea
Vomiting
Diarrhoea
Constipation

Less common but potential risks

While less frequent, you must discuss these potential risks with your healthcare provider:

Pancreatitis (inflammation of the pancreas): This is a rare but serious potential side effect.
Gallbladder issues: There might be an increased risk of gallbladder-related problems in some individuals.
Potential for thyroid C-cell tumors: Some GLP-1 receptor agonists have shown this risk in animal studies, but the relevance to humans is still under investigation for specific medications.
Kidney issues: Patients with pre-existing kidney problems should be monitored closely due to the associated risk of acute kidney injury, with symptoms like decreased urination or swelling indicating the need for immediate medical attention.
Worsening of diabetes-related retinopathy in certain patients has also been observed, prompting the need for careful monitoring of any changes in vision.

Hence, it is crucial to consult your doctor before starting any incretin mimetic medication. They can assess your risk factors, weigh the potential benefits against the risks, and determine if these medications are a safe and appropriate treatment option.

Looking ahead, let's peek at some emerging therapies that are pushing the boundaries of what's possible with incretin science.

Emerging incretin mimetics for diabetes and obesity

The field of incretin-based therapies is rapidly evolving, with several exciting new medications and approaches on the horizon, promising greater efficacy in managing weight and type 2 diabetes. Here are some of the notable emerging incretin mimetics:

Tirzepatide (Mounjaro, Zepbound): This is a novel dual GLP-1 and GIP receptor agonist. By activating both incretin pathways, it has demonstrated impressive results in clinical trials, often leading to greater weight loss and improved blood sugar control compared to GLP-1 receptor agonists alone.
Oral semaglutide tablets (Rybelsus): The development of an oral formulation offers a more convenient option for patients with type 2 diabetes. This can improve adherence and broaden the accessibility of GLP-1 therapy.
Retatrutide: This investigational drug is a triple agonist, targeting GLP-1, GIP, and glucagon receptors. It offers more comprehensive metabolic improvements, such as noteworthy weight loss and better insulin sensitivity.
CagriSema: This is an investigational once-weekly co-formulation of a GLP-1 receptor agonist (semaglutide) and a long-acting amylin analogue (cagrilintide). It aims to provide enhanced glucose control and weight reduction.
Orforglipron: This is an oral GLP-1 receptor agonist currently under development. If successful, it could significantly impact the treatment landscape for both type 2 diabetes and obesity due to its ease of administration.

The discovery of incretins has transformed your understanding of metabolic health, revealing a powerful, natural pathway to regulate blood sugar, appetite, and weight. These gut hormones offer immense promise, and ongoing research continues to unveil exciting new therapeutic avenues.

If you're managing type 2 diabetes or obesity, learning about incretins and the potential of incretin mimetics could be a game-changer. Consult with your healthcare provider to see if they might be a suitable option for you.

Consider nourishing your gut microbiome for a more holistic approach to maintaining your metabolic well-being. The Good Bug offers an array of products, resources, and expert insights to help you take charge of your gut health. Visit our website to order the right probiotics for your needs!