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GLP-1 Comparison

Cagrilintide vs Semaglutide: Amylin vs GLP-1, Compared

These two aren't really rivals — they target two different appetite hormones, share an almost identical weekly half-life, and were engineered to be combined into a single injection. Here is what each does, and why CagriSema exists.

By Halflife Labs Editorial TeamPublished June 8, 202611 min read
Pharmacokinetic and trial figures cross-checked against the NEJM 2025 CagriSema reports, the Lancet 2021 Phase 2 data, FDA prescribing labels for semaglutide, and Novo Nordisk regulatory disclosures. Educational information only — not medical advice. Cagrilintide is investigational.
Direct answer: Semaglutide is an FDA-approved GLP-1 receptor agonist (Ozempic, Wegovy, Rybelsus). Cagrilintide is an investigational amylin analogue — it mimics the satiety hormone amylin, a different pathway. Both have an elimination half-life of about 7 days and are dosed once weekly. Because GLP-1 and amylin are complementary, the two are co-formulated as CagriSema, which produced greater weight loss than either alone.

Side-by-side comparison

PropertyCagrilintideSemaglutide
ClassLong-acting amylin analogue (amylin/calcitonin receptor agonist)GLP-1 receptor agonist
Hormone mimickedAmylin (satiety)GLP-1 (incretin)
Brand namesNone standalone — part of CagriSemaOzempic, Wegovy, Rybelsus
Approval status (Jun 2026)Investigational; CagriSema NDA under reviewFDA-approved
Approximate half-life~7 days~7 days (SC)
DosingOnce weekly (subcutaneous)Once weekly SC · once daily oral
Time to steady state~4–5 weeks~4–5 weeks
Weight loss (matched trials)~11.5% alone; ~22.7% as CagriSema (REDEFINE 1)~14.9% alone (2.4 mg)

See the source-level profiles for cagrilintide and semaglutide, or plot both decay curves with the free half-life calculator.

Mechanism: two appetite hormones, not one

The reason this comparison is so often misunderstood is that both compounds suppress appetite — but through entirely separate hormone systems.

Semaglutide — the GLP-1 lever

Semaglutide mimics GLP-1, an incretin hormone. It stimulates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite through hypothalamic GLP-1 receptors. It shares 94% sequence homology with native GLP-1.

Cagrilintide — the amylin lever

Cagrilintide mimics amylin, a hormone co-secreted with insulin from pancreatic beta cells after eating. It acts on amylin and calcitonin receptors in the brainstem to enhance satiety, slow gastric emptying, and blunt post-meal glucose spikes. Amylin signaling is non-overlapping with GLP-1, which is the entire scientific premise for combining them.

Why the half-lives matter here

Unlike most "versus" peptide pairs, cagrilintide and semaglutide have nearly the same half-life — roughly 7 days each (cagrilintide ~7.3 days; semaglutide ~6.6 days). Phase 1 work confirmed that cagrilintide does not alter semaglutide's exposure or elimination, and vice versa.

The pharmacokinetic insight: matching half-lives are precisely what makes a single weekly co-formulation viable. If one cleared in days and the other in hours, you could not put them in one pen on one schedule. Both also reach steady state in ~4–5 weeks, so their accumulation curves rise in step. Overlay them in the half-life calculator to see the two near-identical decay lines.

Weight loss: alone vs combined

The numbers tell a consistent story — each works, and together they work better:

  • Semaglutide 2.4 mg alone: ~14.9% mean weight loss in matched data.
  • Cagrilintide 2.4 mg alone: ~11.5% mean weight loss.
  • CagriSema (2.4 mg / 2.4 mg): ~22.7% at 68 weeks in the REDEFINE 1 Phase 3 trial.

Hitting two appetite pathways simultaneously yields more weight loss than maximizing either one alone — the additive effect that justified the combination. For people with type 2 diabetes (REDEFINE 2), CagriSema produced a statistically superior result versus placebo, with meaningful HbA1c improvement. For the broader GLP-1 landscape, compare semaglutide vs tirzepatide and retatrutide vs tirzepatide.

Approval and availability

Status check (June 2026): Semaglutide is FDA-approved and widely prescribed. Cagrilintide is not approved as a standalone product and is not sold on its own — it exists clinically only as the amylin half of CagriSema. Novo Nordisk filed an FDA application for CagriSema in December 2025, with a regulatory decision anticipated later in 2026. Material sold online as "cagrilintide" is not an approved medicine.

This shapes any practical decision: semaglutide is something a clinician can prescribe today; cagrilintide is something you will, if approved, most likely receive bundled with semaglutide rather than by itself.

Side effects

Both are dominated by gastrointestinal effects — nausea, vomiting, diarrhea, constipation — concentrated during dose escalation. In CagriSema trials, GI adverse events were common (around 80% of participants) but mostly transient and mild-to-moderate, consistent with the class. A dedicated QT study found cagrilintide did not cause clinically relevant QTc prolongation. As with any GLP-1-based therapy, titration exists specifically to limit these effects.

How they fit the bigger picture

Semaglutide is the established single-pathway GLP-1; tirzepatide adds GIP; retatrutide adds glucagon; and CagriSema takes a different route entirely — pairing GLP-1 with amylin instead of stacking incretins. The full half-life reference for all 44 tracked compounds, including tirzepatide, lives in the compound database, and you can model escalation schedules with the GLP-1 dose-escalation calculator.

Frequently asked questions

What is the difference between cagrilintide and semaglutide?

Semaglutide is a GLP-1 receptor agonist; cagrilintide is an amylin analogue. Different hormones, complementary appetite pathways — which is why they're combined rather than substituted.

Is cagrilintide a GLP-1?

No. It is an amylin analogue. It is paired with the GLP-1 agonist semaglutide in CagriSema, but it acts on different receptors.

Which has a longer half-life?

They're essentially the same — about 7 days each — which is part of why they can share one weekly injection.

Is CagriSema more effective than semaglutide?

In REDEFINE 1, CagriSema reached ~22.7% weight loss at 68 weeks, above semaglutide alone. It targets two pathways at once.

Is cagrilintide FDA approved?

No. Semaglutide is approved; cagrilintide is investigational, and the CagriSema combination's FDA application was filed in December 2025.

Primary sources and further reading

  1. "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity," NEJM (2025)
  2. Lau et al., "Once-weekly cagrilintide for weight management," Lancet (2021), PMID 34562347
  3. FDA, Ozempic (semaglutide) Prescribing Information

Two pathways, one weekly curve. Track it.

Halflife plots real-time concentration curves for cagrilintide, semaglutide, and 42 other compounds — overlay the near-identical decay lines, model steady state, and log injections in one free iOS app.

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