Cagrilintide — Research, Dosing & Price Guide

Cagrilintide is a long-acting acylated amylin analog developed by Novo Nordisk that reduces appetite and food intake by activating amylin receptors in the brainstem — a satiety pathway distinct from and complementary to GLP-1 signaling. When combined with semaglutide in the CagriSema formulation, it has produced the most potent weight loss of any pharmaceutical combination studied in Phase III trials, achieving a mean 22.7% body weight reduction. As a standalone agent, cagrilintide produces meaningful weight loss that validates amylin as a major therapeutic target in obesity.

Cagrilintide is a synthetic analog of amylin, a 37-amino-acid hormone co-secreted with insulin from pancreatic β-cells in response to meals. It activates amylin receptors (AMY1 and AMY3) — heterodimeric complexes of the calcitonin receptor (CTR) with receptor activity-modifying proteins (RAMP1 and RAMP3, respectively). These receptors are concentrated in the area postrema and nucleus tractus solitarius of the brainstem. Activation of brainstem amylin receptors produces three primary effects: (1) slowing of gastric emptying, extending the physical sensation of fullness after meals; (2) suppression of postprandial glucagon secretion from pancreatic α-cells, improving glucose homeostasis; (3) direct satiety signaling to higher brain centers, reducing meal size and food-seeking behavior. The acylation modification (attachment of a fatty acid chain) allows cagrilintide to bind to serum albumin, dramatically extending its half-life and enabling once-weekly dosing. This pharmacokinetic optimization is the same strategy used in semaglutide and liraglutide. Critically, amylin and GLP-1 signal through anatomically and mechanistically distinct satiety pathways — amylin through the brainstem area postrema, GLP-1 through the hypothalamic arcuate nucleus. This means combining cagrilintide with a GLP-1 agonist engages two independent appetite suppression systems simultaneously, overcoming the efficacy plateau seen with single-mechanism agents.

• The STEP UP Phase III trial demonstrated CagriSema achieved 22.7% mean body weight reduction at 68 weeks, compared to 15.8% for semaglutide alone and 8.1% for cagrilintide alone — the largest weight loss reported for any pharmaceutical combination in a Phase III trial.
• 46.9% of CagriSema participants achieved ≥20% weight loss, compared to 25.2% on semaglutide alone — nearly doubling the proportion of patients achieving surgical-grade weight loss.
• Phase II monotherapy data showed cagrilintide produced up to 10.8% body weight reduction at the 4.5 mg dose over 26 weeks — clinically meaningful as a standalone agent.
• Superior glycemic control: CagriSema reduced HbA1c by 2.2 percentage points in type 2 diabetes patients, exceeding both individual components.
• The amylin receptor pathway validated as a complementary target to GLP-1, establishing the scientific basis for dual-mechanism appetite suppression.
• Dose-dependent weight loss with an acceptable GI tolerability profile similar to semaglutide when dose-escalated appropriately.

• Clinical trial doses: 1.2 mg, 2.4 mg, or 4.5 mg subcutaneous injection once weekly. The 2.4 mg dose was used in the pivotal CagriSema Phase III combination trial.
• Dose escalation: Start at the lowest dose (0.25–0.5 mg weekly) and escalate over 8–16 weeks to the target dose. Gradual escalation is critical for minimizing nausea and GI side effects.
• CagriSema combination protocol: 2.4 mg cagrilintide + 2.4 mg semaglutide, co-injected once weekly. Dose escalation applies to both components.
• Research vials (5–10 mg): Reconstitute with bacteriostatic water. Calculate weekly dose based on concentration and desired mg amount.
• Inject subcutaneously in the abdomen, thigh, or upper arm. Rotate injection sites weekly.
• Nausea management during escalation: slow the escalation schedule if nausea is severe. Ginger supplements, small frequent meals, and ondansetron can help.
• No specific food timing requirements, though some users prefer injecting in the evening to sleep through the initial nausea.

Known Side Effects

• Nausea — the most common side effect, affecting 25–45% of patients depending on dose and escalation speed. Most prevalent during the first 4–8 weeks and improving with continued use.
• Vomiting — reported in 10–15% of patients, primarily during dose escalation. Usually resolves with slower titration.
• Diarrhea — affects approximately 10–20% of users, more common at higher doses.
• Constipation — paradoxically reported alongside diarrhea in some patients, reflecting slowed gastric motility.
• Injection site reactions — mild pain, redness, or swelling at the injection site.
• Decreased appetite — technically the desired effect, but in some patients the appetite suppression can be excessive, requiring dose adjustment.
• Potential for pancreatitis — a class-associated risk for amylin analogs, though incidence in clinical trials was very low.

Safety Profile

Cagrilintide's safety profile is well-characterized from Phase II and Phase III clinical trials involving thousands of patients. The GI side effect profile (nausea, vomiting, diarrhea) is consistent with the amylin agonist mechanism and is generally manageable with appropriate dose escalation. Serious adverse events were rare in clinical trials. Contraindications include personal or family history of medullary thyroid carcinoma or MEN2 syndrome (class precaution for peptide-based obesity therapeutics, though the specific risk for amylin analogs is less established than for GLP-1 agonists). History of pancreatitis warrants caution. Not recommended in pregnancy or breastfeeding. Concurrent use with other amylin analogs (pramlintide) or insulin should be carefully managed due to additive hypoglycemic risk. FDA review of the CagriSema combination product is anticipated in 2025–2026.

Weeks 1–4 (escalation phase): GI side effects are most prominent during this period. Appetite reduction begins even at lower doses. Most users notice reduced interest in food, smaller portion sizes, and less snacking. Weight loss of 2–4 lbs is common even during escalation. Weeks 5–12: As the target dose is reached, appetite suppression strengthens. Weight loss accelerates. Nausea diminishes for most users. Typical weight loss is 1–2 lbs per week at this stage. Weeks 13–26: Steady-state weight loss. The rate may slow from the initial pace but remains clinically significant. Metabolic improvements (fasting glucose, HbA1c, lipids) become apparent on blood work. Cagrilintide monotherapy typically produces 8–11% total body weight loss by this point. Weeks 27–68+: Continued gradual weight loss with eventual plateau at a new lower set point. The CagriSema combination data showed 22.7% mean loss at 68 weeks, with some patients achieving >30%. Maintenance dosing is likely required long-term.

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