Cagrilintide

Cagrilintide is a long-acting amylin analog that acts through distinct and complementary pathways to GLP-1 agonists. Human clinical trial data supports its efficacy for weight management.

How It Works (Simplified)

Cagrilintide mimics amylin, a hormone co-secreted with insulin that signals satiety through different brain pathways than GLP-1:

Key Research: Lau DCW et al. (2021) demonstrated -10.8% weight loss with cagrilintide 4.5 mg monotherapy in Phase 2 RCT. PMID:34798060

GRADE meta-analysis (kilograms, not percent)

Khan et al. (PMID:42608559) is a GRADE-assessed meta-analysis of 7 randomised trials (n=8,069) of CagriSema. Versus cagrilintide monotherapy, the pooled mean difference in weight favoured the combination by −9.24 kg (95% CI −10.46 to −8.02). Versus placebo the pooled difference was −13.99 kg (95% CI −18.38 to −9.61). The title names CagriSema; the abstract names cagrilintide as the monotherapy comparator. Figures are pooled kilogram differences, not a cagrilintide-monotherapy percent-weight estimand, and they are not converted to percents here.

Cagrilintide-only arms in Phase 3 trials

REDEFINE 1 is the earlier Phase 3 obesity study with a cagrilintide-only arm (302 of 3,417 randomised; PMID:40544433, NCT05567796). The published abstract describes that arm but reports efficacy numbers only for the combination’s primary comparison. Novo’s annual report gives 11.8% mean weight loss with cagrilintide alone versus 2.3% placebo at 68 weeks if all participants adhered. Those sponsor-reported monotherapy figures use an on-treatment estimand, not the published combination’s treatment-regimen estimand. Novo says RENEW 1 and 2, dedicated Phase 3 monotherapy studies, have started.

REIMAGINE 2, published on 7 June 2026, also carried a cagrilintide monotherapy arm (PMID:42251859, NCT06065540). Of 2,713 adults with type 2 diabetes randomised across 30 countries for 68 weeks, 152 received cagrilintide 2.4 mg on its own, against CagriSema at two strengths, semaglutide at 2.4 mg and 1.0 mg, and placebo.

The trial’s primary comparison was CagriSema against semaglutide, not against cagrilintide, and the published abstract reports adverse-event rates for the monotherapy arm — 82.2%, against 81.2% for semaglutide 2.4 mg and 70.5% for placebo — without an HbA1c figure for it. The monotherapy arm therefore exists in a phase 3 dataset, but its efficacy result is not quoted here because it does not appear in the abstract record consulted; it is reported in the full text, which this review has not read.

Special populations: renal and hepatic impairment

Two phase 1 studies, each giving cagrilintide once, published together in June 2026, tested whether impaired kidney or liver function changes cagrilintide exposure (PMID:42228334). The renal study enrolled 33 participants and the hepatic study 32, each split across normal function and mild, moderate and severe impairment.

Total exposure (AUC to infinity) was similar across all groups, with no consistent pattern by degree of impairment. Against normal renal function, the mean AUC ratios were 1.23 (90% CI 0.91 to 1.66) in mild, 1.18 (0.87 to 1.59) in moderate and 1.21 (0.87 to 1.68) in severe impairment. Against normal hepatic function they were 0.99, 1.01 and 1.11. No serious treatment-emergent adverse events, withdrawals for adverse events, or deaths were reported in either study. The authors state the limitation themselves: the sample sizes are small.

Important Limitations

• Cagrilintide is an investigational compound with no regulatory approvals

• Phase 3 monotherapy arms exist in REDEFINE 1 and REIMAGINE 2; neither was the primary comparison, and dedicated RENEW results remain pending

• The renal and hepatic impairment studies were single-administration phase 1 work in 33 and 32 participants, which is too small to exclude a modest effect

• Phase 3 combination follow-up extends to 68 weeks, but dedicated longer-term cagrilintide monotherapy safety remains unreported here

• A cardiovascular outcomes benefit for cagrilintide monotherapy has not been established

• All clinical trials sponsored by Novo Nordisk (developer)

• No FDA-approved cagrilintide monotherapy product was established in this review

Research Tools

• Cagrilintide Reconstitution Calculator — calculate concentration from vial mass and diluent volume (educational tool only)