Investigational Product • Phase 3 Ongoing

Cagrilintide + Semaglutide ("CagriSema")

A fixed-dose combination of a long-acting amylin analogue and a GLP-1 receptor agonist designed to achieve bariatric-surgery-like weight loss.

Projected Efficacy ~25% Weight Loss

The Concept

Combines Semaglutide (GLP-1 RA) with Cagrilintide (Amylin Analogue). While GLP-1 targets satiety and insulin, Amylin adds additional satiety pathways and delays gastric emptying without hypoglycemia risk.

Phase 2 Signal

In Phase 2 (32 weeks), the combination achieved 15.6% weight loss vs. 5.1% for semaglutide 2.4mg alone (in this specific short-duration trial), demonstrating additive efficacy.

Critical Readouts

The REDEFINE Phase 3 program is currently enrolling. Key readout (REDEFINE 1) expected late 2024/early 2025. Head-to-head vs. Tirzepatide (REDEFINE 4) is highly anticipated.

Mechanistic Rationale: Dual Agonism

CagriSema leverages two distinct physiological pathways to regulate energy balance. Use the buttons below to isolate the effects of each molecule and see how they converge.

Combined Mechanism

CNS / Brain

Dual activation of satiety centers.

Gastric Emptying

Pronounced delay in emptying.

Glycemic Control

Insulin secretion + Glucagon suppression.

Key Synergy: While GLP-1 acts primarily on the hypothalamus and hindbrain to reduce appetite, Amylin targets the area postrema (hindbrain) more specifically. The combination provides "stacked" satiety signals without requiring excessively high doses of either single agent.

Clinical Development Program

Data from Phase 2 trials and the structure of the ongoing Phase 3 REDEFINE program.

Percentage Body Weight Change (32 Weeks)

Source: Frias et al. Lancet 2023. Phase 2 trial, N=92. *Semaglutide 2.4mg arm underperformed historical STEP data (typically ~15% at 68w) due to shorter duration/titration.

Key Findings

Additive Efficacy: The combination outperformed both components individually.
HbA1c Reduction: Similar improvements in glycemic control to semaglutide monotherapy.
Retention: No unexpected safety signals, though GI side effects were numerically higher.

The "Why"

The trial proved that adding Cagrilintide to Semaglutide does not compromise the GLP-1 efficacy and adds independent weight-lowering power.

The REDEFINE Program

The Phase 3 clinical development program for CagriSema is extensive, targeting obesity, type 2 diabetes, and cardiovascular outcomes.

Enrolling / Ongoing

Completed / Past

REDEFINE 1 (Obesity)

Expected Readout: Late 2024 / Early 2025

Pivotal Phase 3 trial. 68 weeks. Comparing CagriSema vs. Placebo vs. Semaglutide vs. Cagrilintide alone.
Primary Endpoint: % Weight Loss.

REDEFINE 2 (T2D)

Expected Readout: 2025

Focus on patients with Type 2 Diabetes. Typically, weight loss is harder to achieve in this population.
Comparator: Semaglutide 1.0mg (Ozempic dose).

REDEFINE 3 (CVOT)

Multi-year Study

Cardiovascular Outcomes Trial. Does CagriSema reduce heart attack/stroke risk more than standard care/monotherapy?

REDEFINE 4 (Head-to-Head)

Crucial Competitive Data

CagriSema vs. Tirzepatide (Zepbound). The battle for "Best in Class" efficacy. Designed to show superiority.

Comparative Landscape

Comparing the projected profiles of leading obesity therapies.

Therapeutic Attribute Profile

CagriSema Tirzepatide Semaglutide

Semaglutide (Wegovy)

The current standard. GLP-1 mono. Proven CV benefit (SELECT trial). ~15% weight loss.

Tirzepatide (Zepbound)

GLP-1/GIP dual agonist. Higher efficacy (~21-22% weight loss). Current efficacy leader.

CagriSema

GLP-1/Amylin. Targeting 25%+ weight loss. Designed to surpass Tirzepatide and bridge gap to bariatric surgery.

Safety & Tolerability Profile

Common Adverse Events (Phase 2 Data)

Percentage of participants reporting events. GI issues are the primary burden.

Nausea Combo: ~58% | Sema: ~30%

Vomiting Combo: ~25% | Sema: ~12%

Discontinuation due to AE Low (< 5% difference)

Note: In clinical practice, titration (slowly increasing dose) is key to mitigating these effects. Phase 2 trials often have aggressive titration schedules that may overstate real-world adverse event rates.

Specific Considerations

Gallstones

Rapid weight loss increases risk of cholelithiasis with all potent anti-obesity meds.

Pancreatitis

Standard warning for GLP-1s. No elevated signal specific to CagriSema seen yet, but monitored.

Heart Rate

Small increase in resting heart rate observed, consistent with GLP-1 class effect.

Analyst Synthesis: Knowns vs. Unknowns

What We Know

The mechanism (GLP-1 + Amylin) is synergistic for weight loss.
Efficacy in Phase 2 exceeded Semaglutide monotherapy.
Safety profile is generally consistent with GLP-1 class, with GI side effects being the main hurdle.

Key Unknowns

Long-term cardiovascular benefits (REDEFINE 3 pending).
Durability of weight loss after drug discontinuation (likely requires chronic use).
Exact head-to-head performance against max-dose Tirzepatide (REDEFINE 4).

The Context

CagriSema represents the "next wave" of obesity care—moving from ~15% weight loss (Wegovy) to potentially ~25%, rivaling bariatric surgery results non-invasively.