Cagrilintide Semaglutide: Phase 3 Results & Safety

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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% 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 an overview of currently approved options, see our Mounjaro vs. Ozempic comparison guide.

Body Composition During Weight Loss

Significant weight changes include both fat and lean mass. A common concern with any substantial weight loss—regardless of method—is preserving muscle and bone while reducing visceral fat (VAT), the deep abdominal fat tied to metabolic risk. A DEXA scan separates fat, lean, and bone and estimates VAT, providing objective data to understand what's changing.

• Learn more about tracking visceral fat with a DEXA scan.
• For general strategies on preserving lean mass during weight loss, see our guide to preventing muscle loss.

Managing GI Side Effects (GLP-1 Class)

GI side effects are common across GLP-1–based therapies. The following general strategies are frequently discussed in clinical settings—always follow your clinician's specific guidance:

• 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—discuss with your prescriber.

Most GLP-1 class GI effects improve with time and careful titration, a pattern observed with CagriSema as well (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 see weight loss?
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). For general strategies on preserving lean mass during weight loss, see our guide to preventing muscle loss.

The BodySpec Take

CagriSema's Phase 3a results documented significant average 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). The therapy remains investigational and is not FDA-approved. Consult a qualified healthcare provider to discuss whether any weight management medication is appropriate for your situation.

Regardless of what approach you and your healthcare provider choose, objective body composition data can help you understand what's changing over time—including whether you're preserving lean mass and reducing visceral fat.

Book a BodySpec DEXA scan to establish a baseline and track changes over time.

Educational content only; not medical or legal advice. BodySpec does not diagnose, treat, prescribe, or sell medications.