GLP-1, GIP and Amylin Compounds Compared

Receptor coverage

The single most useful distinction between these compounds is which receptors they engage. Everything else — mass, durability, dosing cadence — follows from design decisions made after that one.

Compound	GLP-1	GIP	Glucagon	Amylin
Liraglutide	Yes	No	No	No
Semaglutide	Yes	No	No	No
Tirzepatide	Yes	Yes	No	No
Retatrutide	Yes	Yes	Yes	No
Cagrilintide	No	No	No	Yes

Filled = agonist activity reported at that receptor; hollow = not reported. Read down the rows and each compound adds a target the one above it lacks — except cagrilintide, which is not an incretin at all and is included precisely because it breaks the pattern.

What each step actually added

These compounds are usually presented as competitors. They are better understood as a sequence, each solving the problem the previous one left open.

1. Liraglutide — Acylation, proven A fatty acid chain giving reversible albumin binding took the half-life from about two minutes to roughly thirteen hours. Not a large molecule by later standards, but it established that the strategy worked at all — everything below is built on it.
2. Semaglutide — From a day to a week Three changes rather than one: a non-standard amino acid at position 8 blocking DPP-4 cleavage, a substitution at 34 directing acylation to a single site, and a fatty diacid at 26. Same receptor as liraglutide — the advance is entirely durability.
3. Tirzepatide — A second receptor The first compound here to leave the single-receptor design behind, adding GIP agonism to GLP-1 on one molecule. Durability is roughly semaglutide's and achieved the same way; what is new is the second target.
4. Retatrutide — A third receptor Adds glucagon receptor agonism to the previous two. Glucagon is the counter-intuitive inclusion — it raises blood glucose, the opposite of what the other two arms do — and the rationale for including it is the substance of the retatrutide article rather than something a table can carry.
5. Cagrilintide — A different hormone entirely Not an incretin at all. Cagrilintide is a long-acting amylin analogue — a separate hormone with a separate receptor — which is why it appears in the literature alongside semaglutide rather than instead of it. It is the one row of the matrix that does not extend the staircase.

Specifications side by side

Half-lives are those reported in the primary literature for each compound and are reproduced from the individual articles. “Investigational” means the compound has not completed regulatory review in any jurisdiction, not that it is unstudied — both investigational compounds here have published trial data.

Reported adverse observations

Worth stating plainly, because it is the one place where these five compounds are not meaningfully different: across the published literature all of them report the same dominant pattern of gastrointestinal effects — nausea, vomiting, diarrhoea, constipation, reduced appetite — dose-related and most pronounced during escalation.

This is a class characteristic rather than a way to tell them apart. The useful distinction is the quality of the evidence behind each statement: for the three approved compounds these observations come from large controlled trials with systematic adverse event collection, which makes them substantially more reliable than the equivalent statement about most compounds in this catalogue. For the two investigational compounds the data are real but the trial record is shorter.

Which one answers which question

• Isolating GLP-1 receptor activity Semaglutide or liraglutide. Both are single-receptor compounds, so any observed effect has one obvious candidate mechanism. Choose between them on durability: liraglutide for a daily cadence, semaglutide for weekly.
• Separating GIP from GLP-1 Tirzepatide against a GLP-1-only comparator. Running tirzepatide alone cannot tell you which arm produced a result; the comparison is the experiment.
• Adding a glucagon arm Retatrutide, with the caveat that it differs from tirzepatide by one receptor and from semaglutide by two — attributing any single finding to the glucagon arm specifically needs both comparators.
• A non-incretin mechanism Cagrilintide. Amylin signalling is a genuinely separate pathway, which is why the published work pairs it with a GLP-1 compound rather than treating it as an alternative.

Individual articles

• Liraglutide · not stocked
• Semaglutide · view product
• Tirzepatide · view product
• Retatrutide · view product
• Cagrilintide · view product

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