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The GLP-1 generation: a plain guide

Semaglutide. Tirzepatide. Retatrutide. The class is real, the results are real, and so are the trade-offs. Here's an honest primer.

Weight loss · 9 min read

GLP-1 (glucagon-like peptide 1) is a hormone your gut releases after a meal. It tells your pancreas to release insulin, your stomach to slow down, and your brain that you're full. GLP-1 receptor agonists — Ozempic, Wegovy, Mounjaro and the research peptides we stock — mimic this hormone with a much longer half-life.

Why they work

They quiet 'food noise' — the constant background thinking about food. They slow gastric emptying so you stay full longer. They improve insulin sensitivity. The combined effect is a sustained caloric deficit without the willpower tax.

The three generations

Semaglutide (single agonist)

Binds GLP-1 only. Trial weight loss: ~15% of body weight at 68 weeks. The first true breakthrough class.

Tirzepatide (dual agonist)

Binds GLP-1 and GIP. Trial weight loss: ~22% of body weight at 72 weeks. Better metabolic effects than GLP-1 alone.

Retatrutide (triple agonist)

Binds GLP-1, GIP and glucagon. Phase 2 trial weight loss: ~24% at 48 weeks. The glucagon arm raises basal metabolic rate.

What to expect

  • First weeks: nausea, constipation, fatigue. This is the gastric-emptying effect.
  • Titrate slowly — every 4 weeks — to manage side effects.
  • Eat protein-forward, hydrate aggressively.
  • Lose muscle if you don't lift. The deficit is real; train accordingly.

Cautions

Not for personal/family history of medullary thyroid carcinoma or MEN 2. Pancreatitis is rare but serious. If you're on insulin or sulfonylureas, talk to your clinician first — hypoglycemia risk.