How Ozempic works
Ozempic mimics a hormone your gut makes every time you eat. Here’s how it works.
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Semaglutide, the drug in Ozempic and Wegovy, copies GLP-1, a hormone your gut releases after meals. Your own GLP-1 lasts about two minutes; semaglutide’s half-life is about a week, so a weekly shot keeps acting on your brain, stomach and pancreas.
How Ozempic works
It copies a hormone your gut releases every time you eat.
What GLP-1 is
A hormone that cells in your gut lining release within minutes of eating.
It works in 3 places
Your brain, your stomach and your pancreas all have GLP-1 receptors.
Your own GLP-1 lasts about 2 minutes
An enzyme called DPP-4 cuts it, and your kidneys clear the rest.
Semaglutide’s half-life is a week
DPP-4 can’t cut it, and a fatty tail makes it stick to albumin, a blood protein. A week after a shot, half is still there.
The first one came from a lizard
In 1992 a scientist found a longer-lasting GLP-1 look-alike in Gila monster venom. It became a drug in 2005.
The stomach empties slower
In a small study of 20 women with PCOS and obesity, half a meal took 171 minutes to leave the stomach, not 118.
What the trials showed
On the Wegovy dose (2.4 mg), adults without diabetes lost 14.9% of their weight in 68 weeks, versus 2.4% on placebo.
The common downsides
Stomach side effects are common, and most of the weight comes back within a year of stopping.
So that’s how.
Health topics are explained for general information only. This is not medical advice: talk to a doctor or pharmacist about your own situation.
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Sources
Slide 1 of 10
- Semaglutide is a GLP-1 receptor agonist, 94% the same as human GLP-1; one injection a weeknovo-pi.com
Slide 2 of 10
- L-cells in the gut lining release GLP-1; levels rise within about 10 minutes of eatingfrontiersin.org
Slide 3 of 10
- Receptors in the brain (appetite), stomach (slower emptying) and pancreas (insulin only when glucose is high, less glucagon)novo-pi.com
- Receptors in the brain (appetite), stomach (slower emptying) and pancreas (insulin only when glucose is high, less glucagon)insight.jci.org
Slide 4 of 10
- Native GLP-1 lasts 1 to 2 minutes; DPP-4 removes its first two amino acids, the kidneys clear itfrontiersin.org
Slide 5 of 10
- Aib at position 8 resists DPP-4; C18 fatty acid at Lys26 binds albumin (more than 99% bound); elimination half-life about 1 week (165 h); present in the circulation about 5 weeks after the last dosenovo-pi.com
- Aib at position 8 resists DPP-4; C18 fatty acid at Lys26 binds albumin (more than 99% bound); elimination half-life about 1 week (165 h); present in the circulation about 5 weeks after the last dosegwern.net
Slide 6 of 10
- Exendin-4 (39 amino acids) found in Gila monster venom in 1992; 16 of its first 30 positions match GLP-1 (53%); its action on the GLP-1 receptor was shown in 1993; exenatide (Byetta) approved 28 Apr 2005scholars.mssm.edu
- Exendin-4 (39 amino acids) found in Gila monster venom in 1992; 16 of its first 30 positions match GLP-1 (53%); its action on the GLP-1 receptor was shown in 1993; exenatide (Byetta) approved 28 Apr 2005drugs.com
Slide 7 of 10
- Half-emptying 171 vs 118 min; 20 women with PCOS and obesity, semaglutide 1 mg vs placebo (Jensterle et al., Diabetes Obes Metab 2023). The Ozempic label calls the effect a minor delay in the early phase after a mealendocrine-abstracts.org
- Half-emptying 171 vs 118 min; 20 women with PCOS and obesity, semaglutide 1 mg vs placebo (Jensterle et al., Diabetes Obes Metab 2023). The Ozempic label calls the effect a minor delay in the early phase after a mealrepozitorij.uni-lj.si
Slide 8 of 10
- STEP 1: semaglutide 2.4 mg (the Wegovy dose), 1,961 adults with obesity or overweight and no diabetes, with lifestyle support, 68 weeks, −14.9% vs −2.4%gwern.net
- SELECT: heart attack, stroke or cardiovascular death 6.5% vs 8.0% (20% lower relative risk) in 17,604 adults with established cardiovascular disease and no diabetesdoi.org
Slide 9 of 10
- Wegovy 2.4 mg vs placebo: nausea 44 vs 16%, diarrhoea 30 vs 16%, vomiting 24 vs 6%, constipation 24 vs 11%novo-pi.com
- STEP 1 extension (327 participants): −17.3% at week 68, −5.6% at week 120, one year after stopping (two thirds regained)discovery.ucl.ac.uk
- Rarer risks on the label include pancreatitis, gallbladder disease, low blood sugar, kidney injury and a boxed warning on thyroid C-cell tumours in rodentsnovo-pi.com