CagriSema Dosing Chart (Cagrilintide + Semaglutide)

The REDEFINE-1 trial used a 16-week titration to the maintenance dose. Both drugs escalate in parallel because they were delivered as a single co-formulated injection. If you are using compounded cagrilintide + semaglutide separately (common in the US while CagriSema awaits FDA approval), the same schedule applies but you inject twice.

Week 1 to 4: 0.25 mg + 0.25 mg - Purpose: build tolerance to combined GLP-1 + amylin signaling - Expected effects: mild appetite suppression, first side effects (nausea, fatigue, soft stools) - Side effect peak: days 2 to 3 after each weekly injection - Expected weight change: 0 to 2 lbs

Week 5 to 8: 0.5 mg + 0.5 mg - Purpose: strengthen signal to both receptor classes - Expected effects: clearer appetite reduction, more sustained fullness - Side effect re-intensification: 2-3 days after first dose at this level - Expected weight change: 3 to 6 lbs

Week 9 to 12: 1.0 mg + 1.0 mg - Purpose: reach near-therapeutic levels; weight loss accelerates - Expected effects: significant food noise reduction, 1 to 2 lb weekly loss - Persistent effects: earlier satiety at meals, reduced snacking - Expected cumulative loss: 8 to 14 lbs by week 12

Week 13 to 16: 1.7 mg + 1.7 mg - Purpose: penultimate step toward maintenance - Expected effects: strong appetite control, body composition changes become visible - Side effects: more pronounced constipation or diarrhea in some patients - Expected cumulative loss: 14 to 22 lbs

Week 17 onward: 2.4 mg + 2.4 mg (maintenance) - Purpose: steady-state therapy for sustained weight loss and maintenance - Expected effects: 1 to 2 lbs per week loss continues through month 6-9 - Plateau point: typically week 52-60 at approximately 22-23% body weight loss - Side effects: typically settle into manageable range by week 20

Slower titration if needed: the schedule above is the trial protocol. Many patients with strong GI side effects extend each phase by an additional 4 weeks. This is safer and widely used in real-world practice. The total duration to maintenance becomes 24 to 28 weeks instead of 16.

Injection technique: if using compounded cagri + sema (two drugs), inject at separate sites or at least 2 inches apart on the same site. Never mix in the same syringe. See best injection sites for tirzepatide for site rotation (same principles apply).

Picture your pancreas after lunch. Beta cells release two hormones at the same time: insulin and amylin. Insulin is the truck delivering glucose to your cells. Amylin is the dispatcher on the radio telling the kitchen to stop sending orders so the trucks do not pile up at the loading dock. Both are essential. Either one alone leaves the system unbalanced.

Translated to physiology, amylin slows gastric emptying via vagal afferents, suppresses post-meal glucagon spikes from pancreatic alpha cells, and signals satiety to your hypothalamus through the area postrema. The result: food stays in your stomach longer, your liver dumps less stored glucose, and your brain registers fullness sooner. People with type 2 diabetes secrete less amylin than healthy controls, which is one reason their post-meal glucose curves run high and their hunger returns fast.

Cagrilintide is a long-acting amylin analog. Engineers swapped a few amino acids and added a fatty acid chain so it binds both amylin and calcitonin receptors (the dual binding profile gives it a longer half-life and stronger central effect than native amylin). At the receptor level, cagrilintide activates the AMY1, AMY2, and AMY3 receptor complexes (Lau et al., 2021). Once-weekly dosing covers the full feeding cycle because the molecule stays bound to circulating albumin for roughly 6 to 8 days.

The mechanistic reason the combo with semaglutide makes sense: amylin slows the stomach via vagal nerve signaling from the gut wall, while GLP-1 acts on brainstem satiety centers and pancreatic beta cells. Two non-overlapping satiety brakes pulling on different cables. You feel full faster (amylin), and you stay full longer (GLP-1). For the full mechanism of the GLP-1 side, see /peptides/semaglutide. For the amylin pathway in isolation, see /peptides/cagrilintide and cagrilintide weight loss dosage.

You are weighing whether the combo is worth the extra side effect burden, and the answer lives inside one trial. REDEFINE-1 is the Phase 3 study that put CagriSema on the regulatory map. Picture the trial roster: 3,417 adults with obesity (BMI ≥ 30) or overweight with at least one weight-related comorbidity (BMI ≥ 27), randomized across four arms, tracked for 68 weeks (Garvey et al., 2025).

The randomization design: cagrilintide 2.4 mg + semaglutide 2.4 mg (the combination), cagrilintide 2.4 mg alone, semaglutide 2.4 mg alone, and placebo. All four groups started at 0.25 mg of each active drug and titrated up every 4 weeks across the same 16-week ramp described in the schedule above. The primary endpoint was percent change in body weight at week 68.

Headline results, all from the published trial: - CagriSema combination: 20.4% mean weight loss at week 68 - Semaglutide 2.4 mg alone: 14.9% - Cagrilintide 2.4 mg alone: 11.5% - Placebo: 3.0%

The combo delivered roughly 37% more weight loss than semaglutide monotherapy in absolute percentage points. That gap is the entire commercial argument for filing CagriSema as a new product instead of just keeping semaglutide on the market. Secondary endpoints also favored the combination: 40.4% of CagriSema patients achieved ≥25% weight loss vs 16.2% on semaglutide alone. Waist circumference dropped 17.3 cm on the combo vs 13.8 cm on semaglutide.

What this means for you: if you respond like the average trial participant, expect roughly 37% more weight loss than semaglutide alone over 16 months. That is *average*. Individual response varies wildly. The top quartile of CagriSema responders hit 30%+ weight loss, while non-responders (about 15% of the combo arm) stayed under 5%. Same drug, same dose, vastly different outcomes. Whether you respond depends on adherence to the titration, baseline gut microbiome, and a handful of poorly understood genetic factors. For week-by-week response curves on the semaglutide side, see semaglutide results week by week. For visual progress benchmarks at similar weight loss percentages, see men before and after tirzepatide.

You are looking at two protocols on paper and trying to decide which one your prescriber should write for you. The choice is not just "more weight loss" vs "less weight loss." You are trading efficacy for side effect burden, cost, and access. Here is the comparison stripped of marketing language.

The tradeoff in plain terms: you get roughly 5.5 absolute percentage points more weight loss with CagriSema, at the cost of 10 more percentage points of nausea, 9 more points of diarrhea, and a 45% relative bump in discontinuation rate. If your goal is the 10 to 15% weight loss range, semaglutide alone gets you there with a friendlier side effect profile and a paved insurance path. The cleanest head-to-head benchmark in the GLP-1 class remains tirzepatide 15 mg, which hit 22.5% mean weight loss at week 72 in SURMOUNT-1 (Jastreboff et al., 2022).

If you have already maxed out semaglutide and the scale stopped moving, the combo offers a path to break the plateau without switching drug classes entirely. The 24.2% of CagriSema patients who hit ≥30% weight loss is the response range you do not get on semaglutide monotherapy. Plug your goal into the peptide cost calculator before committing; the cumulative spend over 12 to 18 months changes the math more than most patients expect.

For the compounded access reality in the US while CagriSema awaits approval, see brand reviews like vitastir tirzepatide and citizen meds tirzepatide complete guide. For the cagrilintide + tirzepatide alternative stack (a different GLP-1 backbone), see cagrilintide dosage with tirzepatide.

The rationale for combining cagrilintide and semaglutide is that they target completely different appetite pathways. Hitting both simultaneously produces additive (and in trial data, slightly more than additive) weight loss.

Cagrilintide targets amylin receptors. Amylin is a pancreatic peptide co-secreted with insulin. It slows gastric emptying, suppresses glucagon, and reduces food intake via central hypothalamic signaling. Cagrilintide is a long-acting amylin analogue engineered with a fatty acid albumin-binding chain to support once-weekly dosing (Kruse et al., 2021). In a phase 2 dose-finding trial, cagrilintide 2.4 mg achieved 10.8% weight loss at 26 weeks (Lau et al., 2021).

Semaglutide targets GLP-1 receptors. GLP-1 is a gut-derived incretin hormone. It slows gastric emptying, increases satiety via hypothalamus, stimulates insulin release (glucose-dependent), and suppresses glucagon. Semaglutide 2.4 mg weekly produced 14.9% mean weight loss at week 68 in the STEP-1 trial (Wilding et al., 2021).

Combined mechanisms: - Both slow gastric emptying (physical fullness) - Both reduce food intake (central signaling) - Both suppress glucagon (metabolic effect) - Different receptor classes, no competition - Half-lives align (cagrilintide 6-8 days, semaglutide 7 days) → once-weekly combined dose

Why the REDEFINE-1 result exceeded simple addition: - Semaglutide alone: 14.9% (STEP-1 data) / 16.1% (REDEFINE-1 comparator) - Cagrilintide alone: 11.8% - Simple addition: ~25.8% → REDEFINE-1 observed 22.7%, slightly below pure addition - Suggesting partial but meaningful synergy with some receptor cross-talk or overlap

CagriSema vs tirzepatide head-to-head: - CagriSema: 22.7% at 68 weeks (REDEFINE-1) - Tirzepatide 15 mg: 22.5% at 72 weeks (SURMOUNT-1) - Retatrutide 12 mg: 24.2% at 48 weeks (Phase 2)

At the current state of the evidence, CagriSema and tirzepatide are essentially tied, with retatrutide (a triple agonist) narrowly ahead. For comparison detail, see retatrutide vs tirzepatide.

CagriSema's side effects are dominated by the combined GI burden of amylin and GLP-1 signaling.

REDEFINE-1 side effect data (68 weeks): - Any gastrointestinal adverse event: 79.6% - Nausea: 48.1% (vs 38.3% semaglutide alone) - Diarrhea: 27.3% (vs 18.1%) - Constipation: 22.4% (vs 13.2%) - Vomiting: 19.5% (vs 14.7%) - Injection site reactions: 9.8% (similar to monotherapy)

Most events were mild to moderate and transient. Severe GI events occurred in 12.3% of CagriSema patients vs 8.7% on semaglutide alone. Discontinuation rate for side effects: 4.2% (slightly higher than semaglutide alone at 2.9%).

Phase-by-phase expectations:

• Weeks 1-4: Mild nausea (25-35% of patients), soft stools, fatigue. Resolves within 2-3 days of each injection.
• Weeks 5-8: First-time nausea increase for many patients (escalation triggers). Typically 48-72 hour window.
• Weeks 9-12: Side effect adaptation begins; most patients report stable tolerance.
• Weeks 13-16: Third escalation triggers another side effect bump; 5-7 days of harder tolerance.
• Weeks 17+: Maintenance. Side effects stabilize. Constipation becomes more common than nausea at steady state.

Less common but important side effects: - Thyroid C-cell tumors: same boxed warning as semaglutide. Contraindicated in MEN-2 and medullary thyroid cancer history. - Pancreatitis: rare; discontinue if severe persistent abdominal pain. - Gallstones: roughly 4% incidence at rapid weight loss, consistent with both component drugs. - Hair shedding: 3-6% around months 3-6, usually resolves with weight stabilization.

For the full side effect framework that applies to both drug components, see does semaglutide cause nausea, does semaglutide cause hair loss, and does semaglutide cause fatigue.

CagriSema is a specific Novo Nordisk product: cagrilintide co-formulated with semaglutide in a single vial or pen for one weekly injection. In the US, CagriSema is not FDA-approved; the NDA was filed December 2025 and approval is expected 2026-2027.

Many compounding pharmacies currently offer "CagriSema" protocols that are actually two-drug stacks: cagrilintide and semaglutide prescribed and injected separately on the same day. These are not the same product.

Key differences:

Implications for the dosing chart: - With CagriSema proper, the ratios are locked at 1:1. You cannot dose cagrilintide 1.7 mg + semaglutide 2.4 mg (for example) because the drug is a single formulation. - With compounded two-drug protocols, you can titrate each independently. Some patients escalate semaglutide faster because they tolerate it, or hold cagrilintide at 1.0 mg because of amylin-specific nausea. - Side effect management is different: if cagrilintide is driving the nausea, you can drop only cagrilintide in a compounded protocol. With co-formulated CagriSema, you must drop both.

What the compounded protocol looks like (alternative titration):

This alternating pattern spreads side effects and gives flexibility. For regulatory context on compounded peptides, see is compound tirzepatide safe, FDA peptide crackdown, and are peptides legal.

Absolute contraindications: - Personal or family history of medullary thyroid carcinoma - Multiple Endocrine Neoplasia syndrome type 2 (MEN-2) - History of pancreatitis - Hypersensitivity to either component - Pregnancy or breastfeeding (both components lack safety data)

Strong cautions: - Type 1 diabetes (not indicated; may be added to insulin in some investigational contexts) - Severe gastroparesis (both drugs slow gastric emptying; may worsen symptoms) - History of diabetic retinopathy (rapid glucose normalization can transiently worsen) - Gallbladder disease or frequent stones - Age > 75 (limited data in elderly patients)

Drug interactions to watch: - Oral medications taken within 2 hours of injection may have reduced absorption (consistent with all GLP-1s) - Warfarin: INR may shift during weight loss; monitor closely - Thyroid medications: dose may need adjustment as body weight changes - Oral contraceptives: efficacy may decrease at high weight loss rates; use backup methods

When to stop immediately: - Persistent severe abdominal pain (rule out pancreatitis) - Signs of severe dehydration (requires IV fluids) - Neck mass or dysphagia (rule out thyroid pathology) - New suicidal ideation or severe mood changes (both drugs carry warnings)

For GLP-1-class contraindications and monitoring parameters, see tirzepatide drug interactions and tirzepatide long-term side effects. For safer alternatives if CagriSema is contraindicated, see cagrilintide weight loss dosage (monotherapy), retatrutide vs tirzepatide, and survodutide vs tirzepatide.