Cagrilintide + Semaglutide

This vial holds two long-acting peptides freeze-dried together: 5 mg of cagrilintide, an amylin analogue, and 5 mg of semaglutide, a GLP-1 receptor agonist, 10 mg in total. Each carries a fatty diacid side chain for albumin binding, but they act on separate receptor systems. The pairing matches CagriSema, the combination studied in phase 1b and phase 3 trials that measured body weight in adults with overweight or obesity, with and without type 2 diabetes.

Two peptides in one vial

The safety data sheet lists the contents as 50% cagrilintide and 50% semaglutide by mass, 5 mg of each. Equal mass is not equal moles. Cagrilintide's theoretical mass is 4409.0 Da and semaglutide's is 4113.6 Da, so the vial holds about 1.13 µmol of cagrilintide and 1.22 µmol of semaglutide, a molar ratio of roughly 1 to 1.07.

The two are easy to tell apart analytically. Cagrilintide has 37 residues, a disulfide between cysteines 2 and 7, an amidated C-terminus and a C20 diacid on its N-terminal lysine; semaglutide has 31 residues, a free C-terminal acid and a C18 diacid on lysine 26. Their masses differ by almost 300 Da, and a blend certificate reports a separate LC-MS mass for each. The sheet carries the hazard classes of both components, Repr. 2 (H361) for each peptide and Carc. 2 (H351) for semaglutide, and asks for storage under lock. For work that needs a different ratio, cagrilintide is also sold alone in Cagrilintide 10mg vials.

What the research covers

Two receptor systems

Semaglutide is a GLP-1 analogue with two amino acid substitutions and a derivatised lysine 26, designed for high albumin affinity and full stability against metabolic degradation¹. Its receptor is expressed in the pancreas, gastrointestinal tract, heart, lungs, kidneys and brain, and GLP-1 receptors in the pancreas and brain have been shown to account for the effects of liraglutide and semaglutide on glycaemic control and body weight². Amylin works through different receptors, multi-subunit complexes of a core receptor protein with receptor activity-modifying proteins, and acts mainly in the circumventricular organs of the brain³. Writing in 2015, Hay and colleagues noted that clinical studies suggested amylin agonists could be useful for weight loss, especially in combination with other agents³.

The combination in trials

The pair was first studied together in a randomised, placebo-controlled phase 1b trial at a single US centre, in adults aged 18 to 55 with a BMI of 27.0 to 39.9 who were otherwise healthy⁴. Six sequential cohorts were each randomised 3:1 to cagrilintide or placebo, in every case alongside semaglutide and without lifestyle intervention, with participants, investigators and sponsor masked⁴. The primary endpoint was the number of treatment-emergent adverse events, with pharmacokinetic endpoints secondary⁴.

Two 68-week phase 3a trials followed. REDEFINE 1 enrolled adults without diabetes who had a BMI of 30 or more, or 27 or more with at least one obesity-related complication, and randomly assigned them 21:3:3:7 to the combination, semaglutide alone, cagrilintide alone or placebo, with lifestyle intervention in every group⁵. Its coprimary endpoints were the relative change in body weight and a reduction of at least 5% from baseline to week 68, assessed with the treatment-policy estimand, and reductions of 20%, 25% and 30% or more were confirmatory secondary endpoints⁵. REDEFINE 2, run in 12 countries, assigned 1,206 adults with type 2 diabetes, a BMI of 27 or more and HbA1c of 7 to 10% in a 3:1 ratio to the combination or placebo, 904 and 302 participants respectively⁶. It used the same two body-weight endpoints, added glycaemic and safety measures, and followed a subgroup with continuous glucose monitoring⁶. The estimated mean change in body weight at week 68 was −13.7% with the combination and −3.4% with placebo⁶.

What is not established

The trials coadministered the two drugs in a clinical setting⁶. None of the cited papers studied a freeze-dried preparation of both peptides, or measured whether the two affect each other's stability in one vial or one solution. The REDEFINE 1 abstract stops before its results; the single-agent arms and the questions they raise are discussed in the cagrilintide and CagriSema guide. Cagrilintide is investigational, and none of this work used SCALE Performance material.

Frequently asked questions

References

1. Lau J, Bloch P, Schäffer L, et al. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015;58(18):7370-80. DOI · PubMed
2. Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019;10:155. DOI · PubMed
3. Hay DL, Chen S, Lutz TA, et al. Amylin: Pharmacology, Physiology, and Clinical Potential. Pharmacol Rev. 2015;67(3):564-600. DOI · PubMed
4. Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021;397(10286):1736-1748. DOI · PubMed
5. Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2025;393(7):635-647. DOI · PubMed
6. Davies MJ, Bajaj HS, Broholm C, et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med. 2025;393(7):648-659. DOI · PubMed