PMID-33894838 – Cagrilintide Semaglutide Phase 1b PK and Safety
Enebo LB, Berthelsen KK, Kankam M, Lund MT, Rubino DM, Satylganova A, Serusclat P. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021;397(10286):1736-1748.
Quick Reference
| Property | Value |
|---|---|
| PMID | 33894838 |
| DOI | 10.1016/S0140-6736(21)00845-X |
| Year | 2021 |
| Journal | The Lancet |
| Study Type | RCT |
| Evidence Level | II |
| Sample | 92 adults, BMI 27.0-39.9 kg/m2, ages 18-55 |
| Peptide(s) Studied | Cagrilintide, Semaglutide |
Key Findings
- Concomitant cagrilintide (0.16-4.5 mg weekly) + semaglutide 2.4 mg weekly was well tolerated
- No pharmacokinetic interactions between the two agents
- Body weight reductions were greater with the combination than either agent alone
- Cagrilintide 2.4 mg + semaglutide 2.4 mg showed up to 17.1% weight loss over 20 weeks
- GI adverse events were the most common (nausea, vomiting, diarrhea)
- No new safety signals beyond what was expected from individual agents
Study Design
Randomised, placebo-controlled, phase 1b trial evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics of escalating doses of cagrilintide co-administered with semaglutide 2.4 mg in overweight/obese adults over 20 weeks.
Limitations
- Phase 1b; small sample size (n=92)
- Short duration (20 weeks)
- Healthy overweight/obese population only
- Industry-sponsored (Novo Nordisk)
Clinical Relevance
Established the pharmacological rationale and safety of combining amylin (cagrilintide) and GLP-1 (semaglutide) receptor agonism for weight loss. The absence of PK interactions and the additive/synergistic weight loss effects provided the foundation for the CagriSema development program. This dual-pathway approach represents the next generation of obesity pharmacotherapy.
Related
#research #RCT #cagrilintide #evidence-level-II