Cagrilintide vs Tirzepatide: Amylin vs Incretin

Two very different approaches to the same problem. [[Tirzepatide|10]] hits GLP-1 and GIP receptors, the incretin pathway that most weight loss peptides use. [[Cagrilintide|12]] hits amylin receptors, a completely separate system. Both reduce appetite. Both produce significant weight loss in trials. But the biology underneath is different, and that matters for who responds to what.

How tirzepatide works

Dual incretin agonist. GLP-1 slows gastric emptying and signals satiety to the hypothalamus. GIP improves lipid metabolism and insulin sensitivity. Together they produced 22.5% weight loss at 15mg in SURMOUNT-1 (2539 participants, 72 weeks). The dataset is massive and well-characterized.

How cagrilintide works

Amylin analog. Amylin is co-secreted with insulin after meals from pancreatic beta cells. It signals satiety through the area postrema (brainstem, outside the blood-brain barrier), slows gastric emptying, and suppresses glucagon. Different receptors (AMY1-3 and calcitonin receptors), different brain regions, different signaling cascade than GLP-1.

Phase II (Lau et al., Lancet, 2021, 706 participants): cagrilintide 4.5mg produced about 10.8% weight loss in 26 weeks standalone.

Head to head

Tirzepatide wins on raw numbers. 22.5% vs 10.8%, though the trial durations differ (72 vs 26 weeks). Tirzepatide also has Phase III data; cagrilintide as a standalone is still Phase II.

But the comparison misses the real point. These peptides target different receptor systems. Somebody who plateaus on GLP-1/GIP may respond to amylin agonism. Novo Nordisk is betting on this with CagriSema (cagrilintide + semaglutide), which showed up to 25% weight loss combining both pathways.

Side effects

Both cause GI symptoms (nausea, diarrhea) during titration. Similar severity, similar management (start low, go slow).

Difference: cagrilintide carries a slightly higher hypoglycemia risk in certain contexts (amylin's mechanism) compared to tirzepatide. Tirzepatide has more data on long-term safety.

When to consider each

Start with [[Tirzepatide|10]] if you want the strongest data-backed option with the largest clinical evidence base.

Consider [[Cagrilintide|12]] if you've plateaued on GLP-1 peptides and want to try a different receptor pathway, or if the combination approach (amylin + incretin) interests you.

Not sure which direction? Reach out and we'll walk through it.

This article is for educational purposes. Peptides are intended for research use. Consult a healthcare professional before starting any protocol.