01 / Mechanism

What the combo does.

CagriSema is a fixed-dose combination of two long-acting peptides delivered as a single weekly subcutaneous injection: cagrilintide 2.4 mg and semaglutide 2.4 mg. The GLP-1 (glucagon-like peptide-1) arm — semaglutide — is the same molecule used in Wegovy, with the same mechanism: glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, central appetite reduction.

The novel piece is cagrilintide, an acylated long-acting analog of amylin — the 37-amino-acid peptide hormone co-secreted with insulin by pancreatic β-cells. Amylin's physiological role is to slow gastric emptying, suppress postprandial glucagon, and signal satiety via the area postrema and other brainstem nuclei. Cagrilintide engages amylin receptors (AMY1, AMY2, AMY3 — heterodimers of the calcitonin receptor and RAMP proteins) with a similar half-life to semaglutide, supporting once-weekly co-dosing [Lau 2021].

Mechanistically, the GLP-1 and amylin appetite pathways are largely parallel and additive, not redundant. Amylin acts predominantly in the hindbrain; GLP-1 acts in both hindbrain and hypothalamic centers. In animal and Phase 2 data, combined dosing produces greater weight loss than either monotherapy at maximal dose — the additivity that Novo Nordisk is betting the program on. The pramlintide (Symlin) experience established that mealtime amylin agonism in humans is tolerable and modestly weight-favorable; cagrilintide extends that to once-weekly dosing.

02 / Trial dosing

REDEFINE titration.

Week	Cagrilintide	Semaglutide	Note
1–4	0.25 mg	0.25 mg	Initiation, parallel titration
5–8	0.5 mg	0.5 mg	First step
9–12	1.0 mg	1.0 mg	Second step
13–16	1.7 mg	1.7 mg	Third step
17+	2.4 mg	2.4 mg	Maintenance — REDEFINE target

REDEFINE-1 (obesity, no T2D, 68 wks)

3,417 adults randomized 1:1:1:1 to CagriSema, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo. Mean weight change: −20.4% CagriSema vs. −3.0% placebo. 60% of CagriSema patients achieved ≥20% loss and 23% achieved ≥30% loss [REDEFINE-1 2025].

REDEFINE-2 (obesity + T2D, 68 wks)

1,206 adults randomized 3:1 CagriSema vs placebo. Mean weight change: −13.7% CagriSema vs −3.4% placebo. HbA1c <6.5% achieved by 73.5% on CagriSema vs 15.9% placebo [REDEFINE-2 2025]. Weight effect is consistently smaller in T2D — a class pattern with all GLP-1-based agents.

03 / Expected contraindications

Who is likely excluded.

Personal or family history of medullary thyroid carcinoma (MTC). Black-box class effect from the semaglutide component.
Multiple endocrine neoplasia syndrome type 2 (MEN 2). Same rationale.
Prior pancreatitis. GLP-1 class signal.
Severe gastroparesis. Both amylin and GLP-1 slow gastric emptying — additive effect would be problematic.
Pregnancy. Long half-life of both components requires washout before conception.
Severe gallbladder disease. Cholelithiasis risk with rapid weight loss.

04 / Side effects

What REDEFINE showed.

GI adverse events (~72.5%). Nausea, vomiting, diarrhea, constipation. Higher overall incidence than semaglutide 2.4 mg alone — the additive gastric-emptying delay shows up clinically. Most events transient and mild-to-moderate.
Injection-site reactions. Slightly higher than monotherapy, likely related to the dual-peptide formulation.
Loss of muscle mass. Magnitude consistent with rapid weight-loss class effects; mitigate with adequate protein and resistance training.
Gallstones. Class effect — rises with rapid weight loss.
Modest heart-rate increase (~3 bpm). Class-typical.
Rare: pancreatitis, severe retinopathy progression in pre-existing diabetic retinopathy.

05 / Positioning vs the field

Best-in-class — for now.

Going into the REDEFINE readouts, Novo Nordisk had publicly guided toward ~25% weight loss as the bar CagriSema needed to clear. The 20.4% delivered was a beat against placebo and against either monotherapy, but a meaningful miss against expectations — Novo's stock dropped sharply on the December 2024 topline. That market reaction was about positioning, not absolute efficacy: a 20% weight reduction at 68 weeks is genuinely best-in-class data among approved and near-approved agents as of mid-2026.

The real concern is what's coming behind it. Lilly's retatrutide has now read out Phase 3 weight loss of 28.7% at 12 mg — eight percentage points ahead of CagriSema. If retatrutide files on TRIUMPH-4 and a 2027 launch holds, CagriSema's window as the most-effective approved obesity agent could be measured in months. The strategic case for Novo is that CagriSema layers on top of the existing Wegovy manufacturing and prescriber base, with shared safety language and a familiar titration — a faster path to broad payer access than retatrutide will have.

For patients, the practical question is whether to wait. If retatrutide approval looks 12+ months away and current GLP-1 response is inadequate, switching to CagriSema once available is rational. If retatrutide approval is imminent and there's no urgent medical reason to act, waiting may make sense — but waiting on a drug that hasn't yet been approved is its own risk. See the tirzepatide vs semaglutide comparison for how a similar tradeoff played out in the 2022–2024 era.

06 / Cost (anticipated)

What it will likely cost.

Source	Form	~Monthly cost (USD)	Note
Brand (anticipated)	Combo pen, weekly	$1,300–$1,500	Premium to Wegovy alone
Brand (anticipated, insured)	Combo pen	$25–$100 copay	If covered for obesity
Compounded equivalent	Cagrilintide separately + semaglutide	n/a	Not recommended — cagrilintide not in shortage; no exemption pathway
Clinical trial	Provided	$0	Currently the only legitimate route

Pricing strategy is still publicly unsettled. The most likely scenario is a premium-to-Wegovy list price reflecting the additive efficacy, combined with continued aggressive payer-rebate negotiation to keep out-of-pocket comparable for covered patients.

07 / Key references

The evidence base.

Lau DCW et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet. 2021;398(10317):2160–2172. [Lau 2021]
Frias JP et al. Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet. 2023;402(10403):720–730. [Frias 2023]
Garvey WT et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1). NEJM. 2025. [REDEFINE-1 2025]
Davies MJ et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2). NEJM. 2025. [REDEFINE-2 2025]
Enebo LB et al. 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. [Enebo 2021]
American Diabetes Association. REDEFINE-1 and REDEFINE-2 readouts at ADA Scientific Sessions 2025. Press materials, June 2025. [ADA 2025]

About this profile

Last reviewed against evidence: 2026-05-12. This profile is editorial reference content, not sponsored. Wellness Radar does not run affiliate links on prescription drugs. CagriSema is investigational as of May 2026 — available only through Novo Nordisk's REDEFINE program and adjacent studies. Educational reference, not a prescription.

CagriSema