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Comparison guide

GLP-1, GIP, Glucagon, and Amylin Peptides Compared

A source-backed comparison of semaglutide, tirzepatide, retatrutide, cagrilintide, and related incretin or amylin-based peptide medicines.

By
PD Team
Published
May 23, 2026
Last updated
May 23, 2026
Read time
9 min read
Citations
8 citations
Review
Editorially reviewed by PD Team
Three unlabeled peptide vials with abstract incretin receptor and molecular graphics.

GLP-1 drugs are often discussed as if they are one interchangeable category. The reality is more specific. Semaglutide is a GLP-1 receptor agonist, tirzepatide activates GIP and GLP-1 receptors, retatrutide is designed to activate GIP, GLP-1, and glucagon receptors, and cagrilintide is an amylin analogue commonly discussed alongside semaglutide combination research.

Those receptor differences matter, but they do not make one molecule automatically better in every context. The more useful comparison is evidence stage, approved use, route and formulation, trial population, endpoint, tolerability, and whether a claim comes from a completed human trial or an ongoing registry entry.

Quick Comparison

Peptide Primary receptor logic Status context Evidence context
Semaglutide GLP-1 receptor agonist Approved products exist for type 2 diabetes and chronic weight management in some jurisdictions. Large phase 3 programs and cardiovascular-outcome research.
Tirzepatide GIP and GLP-1 receptor agonist Approved products exist for type 2 diabetes and chronic weight management in some jurisdictions. Large SURPASS and SURMOUNT phase 3 programs.
Retatrutide GIP, GLP-1, and glucagon receptor agonist Investigational; phase 3 obesity and cardiometabolic programs are ongoing. Phase 2 human data plus registry-listed phase 3 trials.
Cagrilintide Long-acting amylin analogue Investigational; studied alone and with semaglutide. Phase 2 and phase 3 cagrilintide/semaglutide studies.

Receptor Logic

GLP-1 receptor agonism is the common anchor for semaglutide and part of the mechanism for tirzepatide and retatrutide. GLP-1 signaling is tied to glucose-dependent insulin secretion, appetite signaling, slowed gastric emptying, and other metabolic effects. That does not mean every GLP-1 receptor agonist behaves identically; formulation, dose range, duration, and trial population still matter.

Tirzepatide adds GIP receptor agonism to GLP-1 receptor agonism. Retatrutide adds glucagon receptor agonism to GIP and GLP-1 receptor agonism. Cagrilintide is different again: it is a long-acting amylin analogue, so the scientific question becomes how amylin-pathway signaling pairs with GLP-1 receptor agonism when used in combination research.

Online shorthand often treats "dual agonist" or "triple agonist" as a ranking system. That is too simple. More receptor targets may change efficacy, tolerability, heart-rate effects, gastrointestinal events, or other signals, but only trials can show how those tradeoffs look in a defined population.

Evidence Map

Semaglutide and tirzepatide sit in a different evidence category from retatrutide and cagrilintide. Semaglutide and tirzepatide have approved products and large phase 3 trial programs. Retatrutide remains investigational, with phase 2 publications and multiple phase 3 registry records. Cagrilintide is also investigational, with studies of cagrilintide alone and cagrilintide coadministered with semaglutide.

A completed phase 3 trial is not the same thing as a phase 2 signal, and neither is the same as a recruiting trial. When comparing these peptides, the table on our clinical trials page is useful because it separates trial status, phase, condition, sponsor, enrollment, and primary outcome rather than mixing all studies into one headline.

Safety And Tolerability Context

Incretin and amylin-based metabolic drugs are commonly associated with gastrointestinal adverse events in trials, but the details differ by molecule, dose escalation, comparator, and population. For investigational agents, the public evidence base is also smaller. That makes it especially important not to turn early trial results into broad consumer claims.

Route and formulation are part of safety interpretation. A registered clinical-trial product, an approved pen, and an online vial using the same ingredient name are not equivalent evidence objects. Published results answer questions about the product and protocol actually studied.

How To Read Claims

The strongest comparison starts with the exact claim. Is someone comparing body-weight change, A1C, cardiovascular outcomes, liver fat, tolerability, discontinuation, or long-term maintenance? Is the claim based on an approved label, a peer-reviewed publication, a company topline release, or a trial registry entry?

For practical reading, separate four questions: what receptor pathway is being targeted, what trial phase supports the claim, what population was studied, and whether the product is approved or still investigational. That structure is more reliable than ranking peptides by hype.

References