CagriSemavsTirzepatide

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

C₂₂₅H₃₄₈N₄₈O₆₈

Molecular Weight

4813.45 g/mol

Half-Life

Approximately 5 days (120 hours)

Bioavailability

~80% (subcutaneous)

CAS Number

2023788-19-2

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
• Decreased Appetite
• Vomiting

Uncommon

• Gallbladder Problems
• Hair Thinning (Telogen Effluvium)

Serious

• Pancreatitis
• Thyroid Tumors (Theoretical Risk)

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

Strong human trials (Phase 3 or FDA approved)

FDA Status

FDA approved for this use

Safety Overview

Tirzepatide has been extensively studied in the SURPASS (diabetes) and SURMOUNT (obesity) trial programs, involving thousands of participants over multiple years. [1][2][3] The FDA approved it after thorough safety review. [5][6] While GI side effects are common (especially during dose increases), they're typically mild to moderate and improve over time. [5][6] Serious adverse events are rare. The SURPASS-CVOT trial is ongoing to evaluate long-term cardiovascular outcomes. [16]

Contraindications

• xPersonal or family history of medullary thyroid carcinoma (MTC)
• xMultiple Endocrine Neoplasia syndrome type 2 (MEN2)
• xHistory of serious allergic reaction to tirzepatide or any GLP-1/GIP medication
• xCurrent or recent pancreatitis
• xPregnancy or planning to become pregnant