GLP-1 Peptides Explained: Semaglutide, Tirzepatide, Retatrutide, and Cagrilintide Compared
“GLP-1” has become shorthand for an entire category of metabolic peptides, but the label undersells what’s actually going on: only one of the four compounds below acts on a single hormone pathway. The others stack additional receptor targets on top, which is the main thing that actually separates them. Here’s how semaglutide, tirzepatide, retatrutide, and cagrilintide differ.
Semaglutide: the single-pathway baseline
Semaglutide is a GLP-1 receptor agonist: it mimics a gut hormone that signals fullness, slows gastric emptying, and helps regulate insulin release. It’s the most clinically studied compound of the four, with a large body of trial data behind it, and it’s the reference point the other three are usually described relative to.
Tirzepatide: adds a second receptor
Tirzepatide acts on two hormone receptors instead of one: GLP-1 and GIP. Both play a role in appetite regulation and insulin response, and head-to-head trial data has generally shown a somewhat stronger effect from the dual-receptor approach than from semaglutide alone, though individual response varies.
Retatrutide: adds a third
Retatrutide goes a step further, targeting GLP-1, GIP, and glucagon. The added glucagon target is thought to contribute an effect on energy expenditure on top of appetite suppression. Early trial data has drawn significant attention for showing a larger average weight reduction than earlier GLP-1-based compounds, but it’s also the newest of the four, with a shorter track record than the others.
Cagrilintide: a different pathway entirely
Cagrilintide isn’t a GLP-1 compound at all: it’s a long-acting amylin analog. Amylin is a separate hormone, released alongside insulin, that also contributes to fullness and slows gastric emptying, but through its own receptor system rather than the GLP-1 pathway. That’s exactly why it’s commonly paired with semaglutide rather than compared against it: combining an amylin analog with a GLP-1 agonist hits two separate pathways at once, which is the strategy behind the Semaglutide & Cagrilintide Stack, and notably, the same combined approach has been studied directly in later-stage pharmaceutical trials under a different name, giving it more direct clinical backing than most stacks.
The short version
| Pathway(s) | Track record | |
|---|---|---|
| Semaglutide | GLP-1 | Most established, largest trial base |
| Tirzepatide | GLP-1 + GIP | Well established, stronger head-to-head data than semaglutide alone |
| Retatrutide | GLP-1 + GIP + glucagon | Newest, promising early data, shortest track record |
| Cagrilintide | Amylin (separate from GLP-1) | Studied combined with semaglutide in later-stage trials |
The pattern across the three GLP-1-based compounds is straightforward: each one stacks an additional receptor target onto the last, and more targets has generally trended toward a stronger metabolic response in trial data, though also less long-term data to back it up. Cagrilintide sits outside that progression entirely, which is why it’s typically discussed as a pairing rather than an alternative. For the mechanics of going from a vial to an actual dose, see the dosing guide.