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Body journey · 7 steps

Inside the body with Exenatide

Exenatide is a lab-made copy of a hormone first found in the saliva of the Gila monster, a large lizard. It acts on the same receptor as the gut hormone GLP-1: it helps the pancreas release insulin when blood sugar is high and slows the stomach. It was approved in the US in 2005 for type 2 diabetes.

Scroll to follow it through the body

  1. 01Skin

    Absorbed from under the skin

    The drug is injected just under the skin and slowly moves into the blood. The twice-daily form peaks in the blood after about two hours.

    For experts +

    After subcutaneous administration in people with type 2 diabetes, exenatide reaches a median peak plasma concentration at 2.1 hours, with similar exposure from abdomen, thigh or upper arm. The extended-release forms embed exenatide in PLGA microspheres, so plasma levels rise gradually over weeks (up to about week 10 for Bydureon BCise) and fall below quantifiable limits about 10 weeks after stopping.[src][src]

  2. 02Bloodstream

    Lasts longer than the natural hormone

    In a study in pigs (animal data), natural GLP-1 was broken down within minutes, while exendin-4 (the lizard version) lasted about ten times longer. In people, exenatide stays in the blood for hours.

    For experts +

    Exendin-4 has Gly at position 2 where human GLP-1 has Ala, and is less prone to enzymatic degradation than GLP-1. In anaesthetised pigs (animal data) exendin-4 had a half-life of about 22 minutes versus about 2 minutes for GLP-1, and its only organ extraction was renal. In people the terminal half-life of the immediate-release form is 2.4 hours.[src][src]

  3. 03Pancreas

    Prompts insulin release when sugar is high

    Exenatide switches on GLP-1 receptors on the pancreas cells that make insulin. They release insulin mainly when blood sugar is high, and the effect fades as sugar comes down.

    For experts +

    Exenatide binds and activates the human GLP-1 receptor, raising cAMP-linked signalling and glucose-dependent insulin synthesis and secretion in beta cells. In humans with type 2 diabetes it restored first-phase insulin response to an intravenous glucose bolus and increased second-phase secretion versus saline; insulin release is predominantly in the presence of elevated glucose, and the normal glucagon response to hypoglycaemia is not impaired.[src]

  4. 04Liver

    Less sugar released by the liver

    Another pancreas hormone, glucagon, tells the liver to release sugar. Exenatide turns glucagon down when blood sugar is high, so the liver adds less sugar to the blood.

    For experts +

    In type 2 diabetes exenatide moderates glucagon secretion and lowers serum glucagon during hyperglycaemia. The label attributes lower glucagon concentrations to decreased hepatic glucose output and decreased insulin demand.[src]

  5. 05Stomach

    Slows the stomach

    Food leaves the stomach more slowly, so sugar from a meal enters the blood more gradually.

    For experts +

    Exenatide slows gastric emptying, reducing the rate at which meal-derived glucose appears in the circulation. The label also notes that exenatide may affect absorption of orally administered medicines.[src]

  6. 06Brain

    Eating less

    Studies in animals and in people show exenatide reduces how much they eat. In trials, people lost only a small amount of weight on average.

    For experts +

    The label states that exenatide reduces food intake in both animals and humans; it does not describe the neural pathway, so the central mechanism is not established by these sources. In the 24-week placebo-controlled monotherapy trial, the mean weight change was -2.9 kg with the higher studied dose versus -1.5 kg with placebo (difference -1.5 kg, 95% CI -2.5 to -0.4). Exenatide is not approved for weight management.[src]

  7. 07Kidneys

    Filtered out by the kidneys

    The kidneys filter exenatide out of the blood, and it is then broken into pieces. Because of this, it is not recommended for people with severe kidney disease.

    For experts +

    Nonclinical studies show exenatide is eliminated predominantly by glomerular filtration followed by proteolytic degradation; mean apparent clearance in humans is 9.1 L/h and apparent volume of distribution 28.3 L. In pigs (animal data) renal extraction of exendin-4 was accounted for by glomerular filtration alone.[src][src]

Schematic animation — real structure where marked

Under the skin

Step 01 of 07

AI-generated illustration · not to scale

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What is real and what is drawn

The scenes are schematic animations made for this page. Shapes, colours, speeds and sizes are chosen to explain, not to measure. Nothing is to scale.

  • Real structure: Experimental structure · cryo-EM 3.7 Å · PDB 7LLL (2022). From “Dynamics of GLP-1R peptide agonist engagement are correlated with kinetics of G protein activation.” Nat Commun 2022. RCSB PDB entry. The coordinates are experimental; the movement into place is illustrative.

Transitions between scales use short clips labelled “AI-generated illustration”. They are generated images, not recordings or simulations.

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