Description

GLP3-R (development code LY3437943) is a synthetic linear peptide designed as a triple agonist of the GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), and glucagon receptors.

• Backbone: It is a 39–amino acid peptide, structurally engineered from the native GIP sequence as its base scaffold.

• Modifications:

  • Strategic amino acid substitutions enhance stability against enzymatic degradation (particularly by DPP-IV).

  • A C-terminal extension includes a fatty acid side chain (C20 diacid) conjugated via a linker to promote strong albumin binding, thereby extending half-life.

• Conformation: These modifications maintain the peptide’s affinity for the GLP-1R, GIPR, and GCGR while prolonging systemic exposure and reducing clearance.

Cagrilintide Peptide: Benefits and Scientific Evidence

Cagrilintide (formerly AM833) is a long‑acting analog of amylin, a hormone co‑secreted with insulin by pancreatic β‑cells. It is engineered to resist fibril formation and bind amylin receptor subtypes with high affinity:contentReference[oaicite:0]{index=0}. By activating amylin receptors in the hindbrain and hypothalamus, cagrilintide reduces appetite and slows gastric emptying, leading to sustained decreases in energy intake:contentReference[oaicite:1]{index=1}.

How Does Cagrilintide Work?

Pre‑clinical studies demonstrate that cagrilintide lowers body weight and fat mass by acting through amylin receptor 1 and 3. In mice, subchronic dosing reduced food intake and body weight while preserving lean mass; these effects were absent in mice lacking receptor activity‑modifying proteins (RAMPs) 1 and 3:contentReference[oaicite:2]{index=2}:contentReference[oaicite:3]{index=3}. Cagrilintide activated neurons in the area postrema and parabrachial nucleus, key brain regions that control satiation:contentReference[oaicite:4]{index=4}.

Clinical Benefits of Cagrilintide

Cagrilintide has progressed to phase II clinical trials for obesity. Key findings include:

• Weight loss as monotherapy: In a dose‑finding trial, once‑weekly cagrilintide produced a dose‑dependent reduction in body weight and waist circumference in people with obesity:contentReference[oaicite:5]{index=5}. A systematic review reported that 2.4 mg cagrilintide achieved weight loss comparable to SemaG 2.4 mg and liraglutide 3 mg, with notably fewer vomiting episodes:contentReference[oaicite:6]{index=6}.
• Synergy with GLP‑1 receptor agonists: Cagrilintide is being developed in combination with SemaG as a dual‑hormone therapy known as CagriSema. The meta‑analysis found that once‑weekly CagriSema (2.4 mg/2.4 mg) resulted in >20 % total body‑weight loss over six months—about 9 % more than SemaG alone:contentReference[oaicite:7]{index=7}. The additive effects stem from targeting both amylin and GLP‑1 receptors:contentReference[oaicite:8]{index=8}.
• Favorable metabolic effects: Cagrilintide and CagriSema improved lipid profiles by lowering triglycerides and very‑low‑density lipoprotein cholesterol and were not associated with hypoglycemia:contentReference[oaicite:9]{index=9}. Pharmacokinetic data show that cagrilintide has a long half‑life (~184 hours) and reaches peak plasma concentration in about 24 hours, making weekly administration feasible:contentReference[oaicite:10]{index=10}.

Potential Advantages Over Other Therapies

Current pharmacologic options for obesity often have limited efficacy or are poorly tolerated. Cagrilintide’s ability to reduce weight with fewer gastrointestinal side effects may improve adherence compared with traditional GLP‑1 receptor agonists:contentReference[oaicite:11]{index=11}. Its extended half‑life allows for once‑weekly dosing, reducing injection burden:contentReference[oaicite:12]{index=12}. These features make cagrilintide—and especially the CagriSema combination—a promising alternative for people unable to tolerate higher‑dose GLP‑1 therapies or for those seeking non‑surgical weight‑loss strategies.

Key Research Articles

For further reading, refer to these PubMed‑indexed studies and reviews:

• Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity – summarizes amylin physiology and the rationale for combining cagrilintide with SemaG:contentReference[oaicite:13]{index=13}.
• Once-weekly cagrilintide for weight management – dose‑finding trial demonstrating dose‑dependent weight loss.
• Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3 – pre‑clinical mouse study showing receptor‑dependent weight loss and reduced fat mass:contentReference[oaicite:14]{index=14}:contentReference[oaicite:15]{index=15}.
• Efficacy and safety of cagrilintide alone and in combination with SemaG (CagriSema) – systematic review and meta-analysis reporting >20 % weight reduction and improved tolerability:contentReference[oaicite:16]{index=16}:contentReference[oaicite:17]{index=17}.

Disclaimer: Cagrilintide is an investigational peptide. The information presented here is for educational purposes only and not an endorsement for self‑administration. Clinical use requires regulatory approval and physician supervision.

PLEASE NOTE THAT ALL PRODUCTS FEATURED HERE ARE INTENDED EXCLUSIVELY FOR RESEARCH AND DEVELOPMENT PURPOSES. THEY ARE NOT DESIGNED FOR ANY FORM OF HUMAN CONSUMPTION. THESE PRODUCTS HAVE NOT UNDERGONE EVALUATION BY THE U.S. FOOD AND DRUG ADMINISTRATION.