Peptide stack
Cagrilintide + Semaglutide (CagriSema)
The one stack on this list with real trial data behind it.
Also known as: CagriSema
Combination has clinical trial data
COMPONENTS in this stack
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Cagrilintide
Long-acting amylin agonist that adds synergistic weight loss on top of GLP-1 drugs.
Investigational (Phase 3) -
Semaglutide
Long-acting GLP-1 receptor agonist that kicked off the modern GLP-1 weight-loss era. FDA-approved for type 2 diabetes and chronic weight management.
FDA-approved
Why these are combined
CagriSema pairs cagrilintide (amylin agonist) with semaglutide (GLP-1 agonist) as a fixed-dose combination, and it's been through actual Phase 3 trials. A meta-analysis of seven RCTs (n=8,069) found it beat semaglutide alone by 7.58 kg and cagrilintide alone by 9.24 kg. The REDEFINE 1 trial confirmed higher rates of hitting anthropometric targets versus either drug solo. Semaglutide itself is an approved drug (Ozempic/Wegovy), not a research peptide, so it doesn't have its own page here.
Mechanism & pharmacokinetics
Unusually for a stack on this page, the pharmacokinetics were matched by design rather than assembled from mismatched parts: both cagrilintide (a lipidated amylin analog) and semaglutide (a lipidated GLP-1 analog) are engineered for roughly week-long half-lives, which is why the fixed-dose co-formulation CagriSema is dosed once weekly, same as either drug alone. Mechanistically they act on separate receptor systems (amylin receptor for cagrilintide, GLP-1 receptor for semaglutide) that both feed into satiety and gastric-emptying regulation through overlapping but non-identical hypothalamic and brainstem circuits — the premise being additive appetite suppression rather than one drug amplifying the other's pharmacology. This is the one stack on this page with actual Phase 3 trial data behind the combination itself, not just each ingredient separately.
Citations
- Maximizing weight loss with CagriSema: a systematic review and GRADE-assessed meta-analysis of randomized controlled trials — Khan et al. 2026
- Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1 — Busetto et al. 2026
- Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis — Nong et al. 2026
Typical community protocol
Trial dosing used a once-weekly subcutaneous injection at a 2.4 mg/2.4 mg target dose, titrated up over several months, matching semaglutide's dosing schedule.
Safety notes
Community notes (anecdotal — not clinical evidence)
The most closely watched combination in obesity medicine right now, and unlike everything else on this page, it's backed by trial data rather than forum logic.