Cagrilintide Semaglutide: Phase 3 Results & Safety

Educational only – not medical advice. Always discuss medications with your healthcare professional.

Key Takeaways

• In adults without diabetes, average weight loss at 68 weeks was -20.4% on CagriSema vs -3.0% on placebo (REDEFINE 1).
• In adults with type 2 diabetes, average weight loss was -13.7% on CagriSema vs -3.4% on placebo; 73.5% reached HbA1c ≤6.5% vs 15.9% on placebo (REDEFINE 2).
• GI side effects were the most common and generally mild-to-moderate:
  • Non-diabetes trial: any GI event in 79.6% on CagriSema vs 39.9% on placebo (REDEFINE 1).
  • T2D trial: any GI event in 72.5% on CagriSema vs 34.4% on placebo (REDEFINE 2).
• CagriSema remains investigational and is not FDA-approved.

What is CagriSema?

CagriSema is the investigational name for the cagrilintide semaglutide combination. It pairs GLP-1 (semaglutide) with an amylin-pathway analog (cagrilintide) to target appetite regulation, satiety signaling, and gastric emptying via complementary pathways. In two Phase 3a trials, this dual strategy produced larger average weight loss than placebo, with improved A1c in T2D (REDEFINE 1; REDEFINE 2).

Regulatory status: The therapy is investigational and not FDA-approved. Availability, labeling, and pricing will depend on future regulatory decisions.

Phase 3a Results at a Glance (REDEFINE Program)

Safety and Tolerability

Findings below reflect the two Phase 3a trials, REDEFINE 1 and REDEFINE 2:

• Gastrointestinal (most common): Symptoms were typically mild to moderate and most noticeable during dose escalation. Any GI adverse event occurred in 79.6% on CagriSema vs 39.9% on placebo in the non-diabetes trial and 72.5% vs 34.4% in the T2D trial. Common symptoms include:

• Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Abdominal pain

How Does CagriSema Compare to Monotherapy?

The REDEFINE 1 trial directly compared the combination against its individual components (REDEFINE 1):

• CagriSema: -20.4%
• Semaglutide alone: -14.9%
• Cagrilintide alone: -11.5%
• Placebo: -3.0%

Head-to-head comparisons versus other modern agents (e.g., tirzepatide) were not part of these trials (ACC Journal Scan). For a broader overview of current options, see our Mounjaro vs. Ozempic comparison guide.

Apply the Data: A Body Composition–First Approach

Significant weight changes include both fat and lean mass. Your goal: lose fat while preserving muscle and bone—especially reducing visceral fat (VAT), the deep abdominal fat tied to metabolic risk. A DEXA scan separates fat, lean, and bone and estimates VAT, giving you objective markers to steer treatment.

• Learn more about tracking visceral fat with a DEXA scan.
• Pair medication with strength training and protein using our guide to preventing muscle loss.

Re-scan every 8–12 weeks during a medication or nutrition phase to confirm you are losing mostly fat, not muscle, and that VAT is trending down. You can book a BodySpec DEXA scan to get a baseline and track progress.

Side-Effect Playbook (Patient-Friendly)

While you should follow your clinician’s guidance, many people find these strategies ease GI effects that can occur with GLP-1–based regimens:

• Eat smaller, lower-fat meals during titration to reduce nausea.
• Hydrate gently (sip steadily; avoid chugging) and stay upright 30 minutes after eating to limit reflux.
• Slow the dose escalation if symptoms linger.

Most GLP-1 class GI effects improve with time and careful titration, a pattern echoed with CagriSema (REDEFINE 1; REDEFINE 2).

Frequently Asked Questions

What makes CagriSema different from semaglutide alone?
Two hormones address complementary targets. GLP-1 modulates appetite and glucose control; amylin supports satiety and slows gastric emptying. In REDEFINE 1, mean weight change at 68 weeks was -20.4% with CagriSema versus -14.9% with semaglutide alone (REDEFINE 1).

Did people without diabetes also benefit?
Yes. The non-diabetes cohort saw approximately 20% average weight reduction at 68 weeks, with higher responder rates across major thresholds (≥10%, ≥20%) versus placebo (REDEFINE 1).

Is CagriSema approved by the FDA?
Not at this time. Regulatory decisions, labeling, and availability will be determined after full review by agencies.

What about cost or insurance coverage?
Cost and insurance details are unknown and will not be available until after regulatory approval and final labeling.

Will CagriSema preserve more lean mass than GLP-1 alone?
Unknown. Published Phase 3a papers focused on total weight and glycemic control; direct lean-mass comparisons to monotherapy were not reported (REDEFINE 1; REDEFINE 2). To protect muscle during weight loss, consider DEXA-guided training and nutrition with our guide to preventing muscle loss.

The Bottom Line

CagriSema’s Phase 3a results show robust weight loss in people with and without diabetes and meaningful A1c improvements in T2D, with a predominantly GI side-effect profile typical of incretin-based therapies (REDEFINE 1; REDEFINE 2). While we await regulatory decisions, you can act now. Prioritize body-composition tracking, protect lean mass, and use DEXA to ensure most of the weight you are losing is the unhealthy kind—especially visceral fat.

Ready to get a precise baseline? Book a BodySpec DEXA scan and track your next phase with data you can act on.