CagriSemavsRetatrutide

Molecular Formula

Cagrilintide C₁₉₄H₃₁₂N₅₄O₅₉S₂ · Semaglutide C₁₈₇H₂₉₁N₄₅O₅₉

Molecular Weight

Two peptides in one pen: ~4409 Da (cagrilintide) + ~4114 Da (semaglutide)

Half-Life

Measured together: cagrilintide 159-195 hours, semaglutide 145-165 hours

CAS Number

1415456-99-3 (cagrilintide) · 910463-68-2 (semaglutide)

Molecular Formula

C₂₂₁H₃₄₂N₄₆O₆₈

Molecular Weight

4731 g/mol

Half-Life

~6 days (allows once-weekly dosing)

Bioavailability

High via subcutaneous injection

CAS Number

2381089-83-2

Common

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Injection site reactions

Uncommon

• Fatigue and dizziness
• Hair loss (alopecia)
• Gallbladder-related disorders

Serious

• Serious adverse events
• Suspected acute pancreatitis
• Hypoglycaemia with insulin or sulfonylureas

Common

• Nausea
• Diarrhea
• Constipation
• Decreased appetite

Uncommon

• Increased heart rate
• Injection site reactions

Serious

• Pancreatitis
• Gallbladder problems

Evidence Level

Strong human trials (Phase 3 or FDA approved)

FDA Status

Not approved anywhere. Submitted to the US FDA for weight management in December 2025 on the REDEFINE 1 and 2 trials; the type 2 diabetes pathway is still being discussed with regulators.

Safety Overview

The safety picture comes from randomised trials with over 4,000 participants exposed to the combination [1][2][3][5]. In REDEFINE 1 (3,417 adults without diabetes), about 4 in 5 people on CagriSema (79.6%) had gastrointestinal events — nausea, vomiting, diarrhoea, constipation or abdominal pain — against about 2 in 5 on placebo (39.9%); most were transient and mild to moderate, peaked during dose escalation, and eased once escalation ended [1]. Any adverse event: 92.3% vs 82.3% on placebo; serious adverse events: about 1 in 10 (9.8%) vs 6.1% on placebo, most commonly hepatobiliary and gastrointestinal disorders; discontinuation of an active drug for adverse events: 5.9% vs 3.5% [1]. Two deaths occurred among the 2,108 people in the combination group; the adjudicated causes were suicide and cancer, and mental-health scores (C-SSRS, PHQ-9) were similar across all four groups throughout the trial [1]. In type 2 diabetes the pattern held: gastrointestinal events 72.5% vs 34.4% on placebo (REDEFINE 2, 1,206 adults) [2]; adverse events 86.9% on the full dose vs 81.2% on semaglutide 2.4 mg alone and 70.5% on placebo (REIMAGINE 2, 2,713 adults) [5]. Heart rate rose slightly (+0.94 beats per minute at week 68, vs +1.17 on semaglutide, -3.31 on cagrilintide and -0.58 on placebo) [1]. In the 32-week phase 2 diabetes trial no level 2 or 3 hypoglycaemia and no fatal events were reported [3].

Contraindications

• xPersonal or family history of medullary thyroid carcinoma (MTC) or MEN 2 — boxed-warning contraindication for the semaglutide component
• xPrior serious hypersensitivity to semaglutide, cagrilintide, or their excipients
• xPregnancy — trials discontinued treatment on pregnancy
• xNot approved anywhere — investigational combination

Evidence Level

Moderate human trials (Phase 1-2)

FDA Status

Research compound

Safety Overview

Retatrutide has shown a generally favorable safety profile in Phase 1 and Phase 2 clinical trials involving over 600 participants [1][6]. Most side effects are gastrointestinal and tend to improve over time [3]. The medication appears well-tolerated when doses are increased gradually. No major safety signals have emerged, but larger Phase 3 trials are still ongoing [3].

Contraindications

• xPersonal or family history of medullary thyroid carcinoma (MTC)
• xMultiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• xPregnancy or planning to become pregnant
• xHistory of severe pancreatitis
• xKnown allergy to GLP-1 receptor agonists