GLP-1

Where it comes from

Made in

L cells in the lining of the ileum and colon, and a small group of neurons in the brainstem

Sent out by

Nutrients, especially sugars and fats, reaching the lower gut after a meal

Acts on

• Pancreatic beta cells
• Pancreatic alpha cells
• Stomach
• Hypothalamus and brainstem

What it does

• Boosts insulin release, but only while glucose is high
• Suppresses glucagon from the alpha cells
• Slows the emptying of the stomach
• Reduces appetite and food intake

In medicine

• Semaglutide and liraglutide are long-acting GLP-1 receptor agonists approved for type 2 diabetes and weight management; dulaglutide for diabetes alone
• Exenatide came from exendin-4, a peptide in Gila monster venom
• Tirzepatide acts on the GLP-1 and GIP receptors together

Beyond the body’s own use

• The trial programme ran far past diabetes. In 17,604 adults with obesity and prior cardiovascular disease but no diabetes, semaglutide cut cardiovascular death, heart attack and stroke from 8.0% to 6.5% over a mean of 40 months ¹; a later trial slowed kidney disease in type 2 diabetes. Both are approved uses
• It has not worked in the brain. The phase 3 evoke and evoke+ trials gave oral semaglutide to 3,808 people with early Alzheimer’s disease for two years and found no slowing of decline against placebo, and the programme was stopped ²
• Exenatide did not slow Parkinson’s disease either: in a 194-person phase 3 trial, movement scores measured off medication at two years worsened as much on exenatide as on placebo ³. The journal has since published an expression of concern about that report ⁵
• Trials in alcohol use disorder and other addictions are running and have not reported; none of that is an approved use
• What happens on stopping is only half known. A year after semaglutide was withdrawn in the STEP 1 extension, 327 participants had regained two-thirds of the weight they had lost and their blood pressure and lipids had drifted back ⁴. No trial has tested a planned stop, a lower maintenance dose, or how best to come off
• Semaglutide and tirzepatide prepared outside the approved supply are not reviewed by any regulator for safety, effectiveness or quality