Semaglutide

Semaglutide is one of the most widely studied weight-loss and diabetes drugs in the world.

Semaglutide is a GLP-1 receptor agonist that copies a natural gut hormone (GLP-1) that helps the body manage hunger and blood sugar. [Source: Peptide Dosing Protocols]

Semaglutide turns on a single target called the GLP-1 receptor. That receptor sits on cells in several different organs, which is why semaglutide affects hunger, blood sugar, the stomach, and the heart all at once.

Two small changes to the natural GLP-1 molecule give semaglutide its long shelf life in the body. First, a tweak in the peptide chain blocks the enzyme (DPP-4) that normally breaks down GLP-1 within minutes. Second, a fatty acid chain lets semaglutide bind to albumin, a protein in the blood. That binding slows clearance and stretches the half-life to about 7 days, which is why one weekly injection is enough.

In the brain, GLP-1 receptors in the hypothalamus and brainstem signal fullness. Semaglutide turning these on reduces hunger and lowers calories eaten. In STEP 1, participants on 2.4 mg lost an average of 14.9% of body weight over 68 weeks.

In the pancreas, semaglutide triggers insulin release - but only when blood sugar is already high. This 'glucose-dependent' behavior makes dangerous low blood sugar much less likely than with some older diabetes drugs. In the SUSTAIN trials, semaglutide cut HbA1c by 1.5-1.9% at the 0.5-1.0 mg doses.

Semaglutide slows how fast the stomach empties. That stretches fullness after meals and blunts blood sugar spikes. It also explains the nausea and vomiting that are most common during dose escalation and usually fade with time.

Semaglutide protects the heart and blood vessels in ways that go beyond weight loss alone. The SELECT trial showed a 20% drop in major heart events (heart attack, stroke, cardiovascular death) in people with obesity and existing heart disease. The benefit appeared even in people who did not lose much weight. [Source: Peptide Dosing Protocols]

Provider notes: [PDP compound] semaglutide