Semaglutide: The Hitchhiking Peptide Behind Ozempic and Wegovy

After every meal, your gut sends out a hormone called GLP-1. It tells your body that food is here. Within minutes, the body cuts it up.

Semaglutide is a lab-made copy built to last for days. Its secret is a clever trick. It hitches a ride, like a small fish clinging to a whale shark.

What it is

A peptide is a short chain of amino acids. Think of amino acids as beads and a peptide as a short bead bracelet. New to this? Start with what a peptide is.

Semaglutide is a bracelet built from GLP-1, your own gut hormone. About 94% of its beads match. You may know it as Ozempic or Wegovy.

Scientists made three smart changes. First, they swapped a bead near the front for one called Aib. An enzyme called DPP-4 snips GLP-1 there, like scissors. Aib helps block the scissors.

Your body does not use Aib to build proteins. It has even been found inside a meteorite.

Next, they hooked a fatty tail onto one bead. Then they swapped one more bead, so the tail sticks in a single spot.

What it does in the body

Like GLP-1, semaglutide works through a receptor on cells. A receptor is a lock, and the peptide is the key.

When blood sugar is high, the key nudges the pancreas. It lets out more insulin and less glucagon. Insulin pulls sugar out of the blood. Glucagon pushes blood sugar up.

It also slows how fast the stomach empties. And the GLP-1 lock sits in brain areas that help control appetite.

Now for the fatty tail. It grabs albumin, a big protein in the blood. More than 99% of it rides on albumin, like that little fish on the shark.

Riding along slows how fast the kidneys and enzymes clear it. Half of it is still in the blood about a week later.

There is a daily pill, too. A helper in the tablet shields it from stomach enzymes, so some can soak in. Learn more in why peptides aren't pills.

What scientists have found

In cells: Scientists tested many tails in hamster cells that carry the human GLP-1 lock. Adding albumin made the keys work more weakly. Albumin held on to them, so fewer reached the lock.

The makers needed balance. The tail had to grip albumin but still let the key work. Semaglutide's tail gave the best mix.

In animals: Obese rats could pick plain food or chocolate for 77 days. On semaglutide, they ate less, mostly by eating less chocolate.

In mice, scientists tagged it with a glowing dye. It reached several brain areas linked to eating.

In mice bred to clog their arteries on a fatty diet, it slowed the buildup of plaque.

In people: The big human trials brought striking results. STEP 1 had 1,961 adults with obesity, or extra weight plus a health problem. None had diabetes. For 68 weeks, they took semaglutide or a placebo, a dummy look-alike.

Weight fell 14.9% on semaglutide and 2.4% on placebo. Nausea and diarrhea were the most common side effects.

SELECT followed 17,604 people with heart disease and extra weight, but no diabetes. Over about three years, a heart attack, stroke or heart death struck 6.5% on semaglutide and 8.0% on placebo.

FLOW tested 3,533 people with type 2 diabetes and kidney disease. The risk of serious kidney events, or death from kidney or heart causes, was 24% lower on semaglutide.

Where it stands

Semaglutide has been an FDA-approved medicine since 2017, first as Ozempic for type 2 diabetes. Ozempic is now also approved to lower kidney and heart risks in some of these adults.

As Wegovy, it is approved for long-term weight management in some adults and teens 12 and up. It is also approved to lower heart risks in some adults. And it is approved for MASH, a liver disease with fat and scarring.

How exactly does it lower heart risk? Researchers still want to know. The mouse plaque studies are one clue, and cracking it is the exciting next step.

The bottom line

• Semaglutide is a lab-made copy of the gut hormone GLP-1. A swapped bead helps block the body's scissors.
• A fatty tail lets it ride on albumin, a big blood protein, so it lasts for days instead of minutes.
• FDA-approved since 2017, it has been tested in big trials on weight, heart and kidneys.