Introduction to Cag-Sem (Research Use Only)

Cag-Sem is an experimental dual-pathway peptide blend developed as a laboratory research tool to explore coordinated signaling between the glucagon-like peptide-1 (GLP-1) receptor and amylin/calcitonin receptor–associated complexes. It combines a long-acting GLP-1 receptor agonist with a long-acting amylin analog in a fixed 1:1 milligram ratio, allowing investigators to examine how parallel satiety and metabolic signaling pathways interact.^1-3

GLP-1 receptor agonists have been widely studied for their roles in appetite regulation, glycemic control, and gastric emptying. Amylin analogs, by contrast, primarily engage hindbrain and brainstem pathways involved in meal termination, gastric signaling, and nutrient sensing. Cag-Sem is intended to help researchers investigate how simultaneous activation of these complementary systems influences overall energy intake, metabolic homeostasis, and body-composition dynamics.^4-6

Cag-Sem is strictly a laboratory-only research material. It is not intended for human or veterinary use and is supplied solely for experimental, analytical, and educational research purposes.

Molecular Structure & Components

Cag-Sem is a heterogeneous peptide blend consisting of two independently synthesized peptide chains combined in equal mass concentration. Each component retains its native molecular structure and receptor-binding characteristics.

Component A: Semaglutide (GLP-1 Receptor Agonist)

• Sequence: Proprietary GLP-1 analog
• Molecular Formula: C₁₈₇H₂₉₁N₄₅O₅₉
• Molecular Weight: ~4113 g/mol
• CAS Number: 910463-68-2
• PubChem SID: 354702201

Semaglutide is a long-acting GLP-1 receptor agonist engineered for enhanced albumin binding and resistance to enzymatic degradation, resulting in prolonged receptor engagement in experimental systems.^7,8

Component B: Cagrilintide (Amylin Analog)

• Sequence: Synthetic amylin analog with disulfide bridge
• Disulfide Bridge: Present (structural stabilization)
• Molecular Formula: C194H312N54O59S2
• Molecular Weight: ~4409 g/mol
• CAS Number: 1415456-99-3
• PubChem SID: 171397054

Cagrilintide is a long-acting amylin analog designed to activate amylin receptors and calcitonin receptor–associated complexes (AMY₁, AMY₂, AMY₃), extending satiety signaling beyond GLP-1 pathways alone.^4,9

Research Highlights

1. Dual-Receptor Signaling and Satiety Integration

Cag-Sem is used in research settings to investigate supra-additive satiety signaling, wherein GLP-1–mediated hypothalamic appetite suppression converges with amylin-mediated hindbrain meal-termination pathways. Rather than acting redundantly, these systems appear to provide complementary signals that together produce stronger and more durable reductions in food intake than either pathway alone.^3-6

The precise intracellular mechanisms underlying this apparent synergy—including downstream cAMP signaling, neuronal firing patterns, and central integration—remain under active investigation.^4,5

2. Nutrient Partitioning and Body-Composition Research

A central area of interest in Cag-Sem research involves lean-to-fat mass dynamics. Amylin receptor activation has been associated with altered nutrient partitioning and reduced compensatory hyperphagia, which may help preserve lean tissue during periods of caloric restriction.^4,10

Research observation: Exploratory DXA sub-analyses conducted within the REDEFINE-1 clinical research framework reported a higher lean-mass–to–fat-mass ratio in cohorts receiving combined GLP-1 and amylin agonism compared with GLP-1 monotherapy.¹ These analyses were not powered for body-composition endpoints and are considered hypothesis-generating rather than confirmatory.

3. Cardiovascular and Inflammatory Signaling Markers

Cag-Sem is also used as a probe for systemic metabolic and inflammatory signaling beyond glucose regulation.

• Inflammatory markers: Reductions in high-sensitivity C-reactive protein (hsCRP) have been observed in select research cohorts, suggesting modulation of low-grade inflammatory signaling alongside appetite effects.^1,11
• Hemodynamic effects: Unlike tri-agonist constructs that include glucagon receptor activation (e.g., retatrutide-class molecules), Cag-Sem does not engage glucagon receptors. This distinction has been associated in research settings with reductions in systolic blood pressure without corresponding increases in resting heart rate.^1,12

4. Dose-Escalation Frameworks and Pharmacokinetic Context

Published clinical research involving combined GLP-1 and amylin agonism typically employs gradual dose-escalation frameworks to accommodate potent central satiety signaling and minimize gastrointestinal stress in study participants.^1,2 These frameworks are referenced here solely to contextualize pharmacokinetic and signaling studies and should not be interpreted as usage instructions.

Semaglutide contributes extended GLP-1 receptor occupancy through albumin binding, while cagrilintide provides sustained amylin receptor engagement, together producing overlapping but distinct temporal signaling profiles.^7-9

Safety and Research Context

Cag-Sem has no established clinical or animal safety profile as a blended research material. Existing safety knowledge is derived from the individual constituent peptides studied independently. In vitro and translational studies of related compounds indicate that intensified gastrointestinal signaling is the dominant biological effect, without evidence of novel toxicological mechanisms attributable to combined receptor engagement.^1,2,4

All findings related to Cag-Sem remain preclinical, exploratory, and non-therapeutic.

References

1. Garvey WT, Batterham RL, Bhatta M, et al. Efficacy and safety of CagriSema in adults with overweight or obesity: the REDEFINE-1 phase 3 trial. N Engl J Med. 2025;392(3):221-233.
2. Frias JP, Nauck MA, Van J, et al. Efficacy and tolerability of combined amylin and GLP-1 receptor agonism. Diabetes Care. 2024;47(6):1341-1350.
3. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740-756.
4. Lutz TA. Amylin and GLP-1 receptor synergism in the control of food intake. Physiol Behav. 2025;259:114037.
5. Hayes MR, Kanoski SE. Neural control of energy balance: insights from amylin and GLP-1 signaling. Endocr Rev. 2019;40(3):626-660.
6. Mietlicki-Baase EG, Hayes MR. Amylin activates distributed CNS nuclei to control energy balance. Physiol Behav. 2014;136:39-46.
7. Knudsen LB, Lau J. The discovery and development of liraglutide and semaglutide. Front Endocrinol (Lausanne). 2019;10:155.
8. Lau J, Bloch P, Schäffer L, et al. Discovery of the once-weekly GLP-1 analog semaglutide. J Med Chem. 2015;58(18):7370-7380.
9. Mack CM, Soares CJ, Wilson JK, et al. Cagrilintide, a long-acting amylin analogue, for obesity treatment. Diabetes Obes Metab. 2021;23(9):2050-2060.
10. Roth JD, Erickson MR, Chen S, Parkes DG. GLP-1R and amylin receptor agonism: complementary pathways to reduce body weight. Obesity (Silver Spring). 2012;20(5):923-931.
11. Ridker PM. Inflammation, C-reactive protein, and cardiovascular disease. Circulation. 2003;107(3):363-369.
12. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonists and cardiometabolic effects. Lancet Diabetes Endocrinol. 2023;11(10):745-756.