Glucagon

Where it comes from

Made in

Alpha cells of the pancreatic islets

Sent out by

Falling blood glucose, amino acids after a protein meal, adrenaline and exercise; insulin and somatostatin hold it back

Acts on

• Liver
• Fat tissue
• Heart

What it does

• Makes the liver break down glycogen and make new glucose ¹
• Raises energy expenditure and fat burning ¹
• Rises wrongly in type 2 diabetes, adding to the high glucose

In medicine

• Glucagon is the rescue injection for severe hypoglycaemia; a nasal powder (2019) and ready-to-use pens of dasiglucagon (2021) followed ²
• The glucagon stimulation test probes growth hormone and cortisol reserve
• Given to relax the gut during imaging and endoscopy

Beyond the body’s own use

• Glucagon receptor activity is built into the dual and triple agonists survodutide, mazdutide and retatrutide: the glucagon part raises energy expenditure, the GLP-1 part curbs appetite. Mazdutide took off 16.7% of body weight against 1.5% on placebo in a 461-person Chinese phase 3 trial ⁴ and is approved in China for weight management; the others have reported phase 3 results in obesity and are not approved
• Blocking the receptor instead was tried and largely abandoned: in phase 2 trials in type 2 diabetes, glucagon receptor antagonists lowered glucose but raised liver fat, liver enzymes and LDL cholesterol ³
• Pumps that give glucagon alongside insulin, the bihormonal closed loop, are in trials in type 1 diabetes and are not approved