CagriSema

cagrilintide semaglutide

Grade B: Human evidence, not approved for this use

TL;DR: CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg) is an investigational once-weekly fixed-dose combination injection of an amylin analog and a GLP-1 receptor agonist, developed by Novo Nordisk for obesity. The Phase 3 REDEFINE 1 trial (n=3,417, 68 weeks, adults with obesity or overweight with comorbidities, without type 2 diabetes) met its primary endpoint with 22.7% mean weight reduction versus approximately 2.3% with placebo; 60.2% of on-treatment participants achieved at least 20% weight loss, while under the primary treatment-policy estimand, 22.9% achieved at least 20% weight loss. The 22.7% result met the trial's primary endpoint but fell short of the approximately 25% weight loss that had been anticipated in earlier company projections, and is not clearly superior to semaglutide monotherapy in head-to-head comparisons. REDEFINE 1 data were published in NEJM in June 2025. Novo Nordisk filed an NDA with FDA in 2025; the application was under review as of June 2026. Evidence is Grade B due to pending regulatory decision.

Key Takeaways

Grade B: Human evidence, not approved for this use
Not FDA approved: Investigational combination product; NDA filed with FDA in 2025, under review as of June 2026.
Compounding: Not approved by FDA as of June 2026. NDA under FDA review. CagriSema is not eligible for compounding under 503A or 503B as an unapproved combination product; semaglutide is no longer on shortage and is not eligible for compounding except in specific FDA-authorized circumstances.

Mechanism

Combines amylin receptor agonism (cagrilintide, slowing gastric emptying and suppressing appetite centrally) with GLP-1 receptor agonism (semaglutide, stimulating glucose-dependent insulin secretion and suppressing glucagon and appetite) to produce additive weight reduction.

Evidence

CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg) is an investigational once-weekly fixed-dose combination injection of an amylin analog and a GLP-1 receptor agonist, developed by Novo Nordisk for obesity. The Phase 3 REDEFINE 1 trial (n=3,417, 68 weeks, adults with obesity or overweight with comorbidities, without type 2 diabetes) met its primary endpoint with 22.7% mean weight reduction versus approximately 2.3% with placebo; 60.2% of on-treatment participants achieved at least 20% weight loss, while under the primary treatment-policy estimand, 22.9% achieved at least 20% weight loss. The 22.7% result met the trial's primary endpoint but fell short of the approximately 25% weight loss that had been anticipated in earlier company projections, and is not clearly superior to semaglutide monotherapy in head-to-head comparisons. REDEFINE 1 data were published in NEJM in June 2025. Novo Nordisk filed an NDA with FDA in 2025; the application was under review as of June 2026. Evidence is Grade B due to pending regulatory decision.

Safety and risks

Gastrointestinal adverse events in REDEFINE 1 were frequent: 79.6% of CagriSema participants reported GI events versus 39.9% with placebo; nausea occurred in 55% versus 12.6%; constipation in 30.7% versus 11.6%; vomiting in 26.1% versus 4.1%. Most GI events were mild to moderate and transient, peaking during dose escalation. Discontinuation due to adverse events was 6% with CagriSema versus 3.7% with placebo in REDEFINE 1. Because semaglutide is a GLP-1 receptor agonist, the full GLP-1 class safety profile applies: boxed warning for thyroid C-cell tumors (contraindicated in personal or family history of MTC or MEN2); risk of acute pancreatitis, acute gallbladder disease, acute kidney injury from volume depletion, hypoglycemia when combined with insulin or secretagogues, and pulmonary aspiration risk during anesthesia from delayed gastric emptying. The amylin component (cagrilintide) further slows gastric emptying; the clinical significance of combined gastric emptying inhibition on oral drug absorption is not yet fully characterized. Full risk profile pending regulatory review.

Interactions

All GLP-1 receptor agonist interactions apply via the semaglutide component: enhanced hypoglycemia with insulin or secretagogues; delayed gastric emptying may reduce absorption of oral contraceptives and other oral medications requiring consistent absorption. Concomitant use with another GLP-1 agonist is not appropriate. Confirm at prescribing.

Compounding legality

Not approved by FDA as of June 2026. NDA under FDA review. CagriSema is not eligible for compounding under 503A or 503B as an unapproved combination product; semaglutide is no longer on shortage and is not eligible for compounding except in specific FDA-authorized circumstances.

Sources

CagriSema is Not FDA approved. PeptideGrids presents evidence and regulatory status for informational purposes only. We do not sell, supply, source, or help anyone obtain this compound, and we provide no dosing or administration guidance. This is not medical advice; consult a licensed clinician. Full disclaimer.

Last reviewed June 1, 2026 by PeptideGrids editorial team (independently audited).