The Lab

GLP-1 Peptides: Semaglutide, Tirzepatide, and the New Generation

PeptaBase Research Review | 2026-02-07

What GLP-1 Is

GLP-1 is a hormone made by the intestines when you eat. It does several things: tells the pancreas to release insulin (when blood sugar is high), suppresses glucagon, slows stomach emptying, and signals fullness to your brain.

Native GLP-1 breaks down fast-within minutes-thanks to an enzyme called DPP-4. GLP-1 drugs are engineered to survive longer by resisting that enzyme, so they keep the receptor activated.

Semaglutide: Single-Receptor Agonism

Semaglutide (Novo Nordisk) is the original modern GLP-1 drug. It's engineered to stick to albumin in the blood, so it lasts a week-allowing once-weekly dosing.

The SUSTAIN trials (diabetes) and STEP trials (obesity) showed major drops in blood sugar and weight. The SUSTAIN-6 trial even showed it reduced heart attacks and strokes.

It works only on GLP-1. It's good for weight loss, but newer drugs hitting multiple receptors work better.

Tirzepatide: Dual GLP-1 / GIP Agonism

Tirzepatide (Eli Lilly) hits two receptors: GLP-1 and GIP. GIP is another gut hormone that boosts insulin and influences fat metabolism.

The SURPASS trials showed tirzepatide beats semaglutide on weight and blood sugar. SURMOUNT showed 20-22% weight loss in people without diabetes-better than semaglutide.

Double the receptors likely means better effects on appetite and energy, though exactly how much each contributes is still being studied.

Retatrutide: Triple-Receptor Agonism

Retatrutide (Eli Lilly, still in development) is the next generation: it hits GLP-1, GIP, and glucagon. Glucagon revs metabolism and burns energy-adding to the appetite suppression from the other two.

Phase 2 data showed 24% weight loss in 48 weeks-better than tirzepatide. Phase 3 trials are ongoing.

Glucagon can raise blood sugar, but the GLP-1 and GIP effects keep that in check at the doses tested.

The Big Picture

This is one of the fastest-moving areas in peptide research. We have solid clinical data for semaglutide and tirzepatide. Retatrutide is earlier. Unlike most research peptides, these are FDA-approved drugs with huge trial databases.

--- For research use only. Not medical advice.