WEIGHT & METABOLIC COMPARISON
Semaglutide, Tirzepatide, Retatrutide, and Cagrilintide are the leading peptides studied for weight and metabolic research. All four work on the body's fullness signals—Semaglutide, Tirzepatide, and Retatrutide through the incretins, the gut hormones that tell the brain a meal has landed, and Cagrilintide through amylin, a separate satiety hormone—but they differ in which signals they hit, how far along the evidence is, and what they are studied for. CagriSema, the Cagrilintide + Semaglutide combination, hits both routes at once. Compare them side by side.
COMPARE THE PROFILES
Highlight one compound to see its relative profile across the key research dimensions. Bars reflect studied research emphasis and evidence stage, not a guarantee of results.
GLP-1 Agonist
A single-target GLP-1 agonist and the original blockbuster of the class, FDA-approved in its clinical formulations. It has the longest track record and the deepest evidence base here, including a cardiovascular outcomes trial, and is the benchmark the newer compounds are measured against.
Dual Agonist
A dual agonist—it switches on two fullness receptors, GIP and GLP-1—and an FDA-approved medication in its clinical formulations. Adds a second receptor to Semaglutide’s one, studied for weight, glucose, and body composition.
Triple Agonist
A triple GLP-1 + GIP + glucagon agonist reporting the largest weight-loss effects here in trials. Phase 3 complete (not yet approved), with roughly two years of research-market use.
Amylin Agonist
Studied for fullness, but through a separate route: it works on the amylin pathway rather than the incretins, which is why it is researched as a partner to GLP-1 compounds rather than a replacement. Phase 3 data reported, but real-world use is still developing.
Amylin + GLP-1 Combination
CagriSema is Cagrilintide and Semaglutide researched together: the amylin fullness route and the GLP-1 route at once. In the Phase 3 REDEFINE-1 trial the combination reached −22.7%, well beyond either compound alone (−11.8% and −16.1%). It is not a single product—it is the two compounds used together, and the combination is not yet approved.
WHAT THE TRIALS SHOWED
The cleanest single comparison across the leading weight-loss peptides: average weight loss reported in each compound’s trials over a comparable 68–72 week window, at the maximum single-compound dose (for the combination, both at 2.4mg).
| Compound | Trial | Duration | Average weight loss |
|---|---|---|---|
| Cagrilintide 2.4mg | REDEFINE-1 (Cagrilintide alone) | 68 weeks | −11.8% |
| Semaglutide 2.4mg | STEP 1 | 68 weeks | −14.9% |
| Tirzepatide 15mg | SURMOUNT-1 | 72 weeks | −20.9% |
| CagriSema 2.4mg + 2.4mgCagrilintide + Semaglutide | REDEFINE-1 | 68 weeks | −22.7% |
| Retatrutide 12mg | TRIUMPH-4 (Phase 3) | 68 weeks | −28.7% |
These are separate trials with different populations, so the numbers are not a perfect head-to-head.
The one direct comparison that exists points the same way: in SURMOUNT-5, Tirzepatide beat Semaglutide −20.2% to −13.7% at 72 weeks. Retatrutide’s longer TRIUMPH-1 trial reached an average of −30.3% at the highest dose by 104 weeks.
Cagrilintide’s modest solo number is not its whole story. It is studied primarily as a partner to GLP-1 compounds, and the CagriSema combination—Cagrilintide plus Semaglutide—reached −22.7% in the same REDEFINE-1 trial, versus −16.1% for Semaglutide alone.
WHY RESEARCHERS COMPARE THEM
Semaglutide hits one receptor, Tirzepatide two, Retatrutide three, and Cagrilintide works a separate pathway entirely—which is why CagriSema pairs Cagrilintide with Semaglutide.
Two are FDA-approved, two completed Phase 3—the comparison shows how evidence maturity differs even among leading compounds.
Each is rated with the same Evidence Framework, so the bars reflect a consistent standard rather than marketing.
Bars reflect each compound's studied research emphasis and evidence stage relative to the others—not absolute effect sizes or a promise of results. Retatrutide, Cagrilintide, and the CagriSema combination (Cagrilintide with Semaglutide) are investigational and not FDA-approved. All materials are offered strictly for laboratory and research use. See each compound page for its full Evidence Snapshot.
