Retatrutide + Cagrilintide Blend — Research, Dosing & Price Guide

Reta-Cagri Blend combines retatrutide, a triple-agonist GLP-1/GIP/glucagon receptor peptide, with cagrilintide, a long-acting amylin analog. This combination targets multiple metabolic pathways simultaneously — appetite suppression, insulin sensitization, glucagon-mediated fat oxidation, and gastric emptying regulation. The blend represents a next-generation approach to obesity pharmacotherapy, leveraging synergistic mechanisms that individually have shown dramatic weight loss in clinical trials.

Retatrutide activates three distinct receptors: GLP-1R, GIPR, and the glucagon receptor (GCGR). GLP-1R activation suppresses appetite via hypothalamic satiety centers and slows gastric emptying, enhancing post-meal fullness. GIPR agonism improves insulin sensitivity and may enhance the central appetite-suppressive effects of GLP-1. The glucagon receptor component is the distinguishing feature — it increases hepatic fat oxidation, stimulates energy expenditure, and promotes thermogenesis, addressing the metabolic slowdown that often accompanies caloric restriction. Cagrilintide is a long-acting analog of amylin, a hormone co-secreted with insulin from pancreatic beta cells. It binds to the amylin receptor (AMY1/AMY3) in the area postrema and lateral parabrachial nucleus, reducing meal size and promoting satiety through a distinct pathway from GLP-1. It also slows gastric emptying independently and reduces postprandial glucagon secretion. Together, these compounds create a four-receptor assault on obesity — GLP-1R, GIPR, GCGR, and amylin receptors — covering appetite, satiety, energy expenditure, and glucose regulation simultaneously. This multi-target approach may mitigate the weight loss plateau commonly seen with single-mechanism agents.

• Retatrutide Phase II trial (2023, NEJM) showed up to 24.2% body weight loss at 48 weeks at the 12 mg dose — the highest recorded for any obesity drug at that time
• Cagrilintide Phase II trial (2021, Lancet) demonstrated 10.8% weight loss at 4.5 mg weekly over 26 weeks as monotherapy
• The CagriSema concept (cagrilintide + semaglutide) achieved ~15.6% weight loss in 32 weeks in Phase II, validating multi-mechanism approaches
• Triple agonism (GLP-1/GIP/glucagon) showed superior hepatic fat reduction vs. dual agonists in preclinical models
• Retatrutide significantly reduced liver fat content (up to 81.4% relative reduction) in Phase II subanalyses
• Amylin analogs have shown independent weight loss effects additive to GLP-1RA therapy in rodent and human studies

• Starting dose: typically low-dose escalation beginning at 0.5 mg retatrutide / 0.25 mg cagrilintide weekly
• Dose titration over 4–8 weeks, increasing every 2–4 weeks based on tolerance
• Maintenance doses vary; retatrutide component may reach 8–12 mg weekly in aggressive protocols
• Administered as a single subcutaneous injection weekly, typically in the abdomen or thigh
• Inject at the same time each week for consistent blood levels
• Best administered in the morning or early afternoon to align appetite suppression with waking hours
• Cycle length: ongoing while weight loss goals are being pursued; no established cycling protocol
• GI side effects are dose-limiting — slow titration is essential to minimize nausea and vomiting

Known Side Effects

• Nausea is the most common side effect, particularly during dose escalation (reported in 40–60% of participants in trials)
• Vomiting and diarrhea are frequent, especially at higher doses or with rapid titration
• Decreased appetite — expected pharmacological effect but can become excessive
• Constipation from slowed gastric motility
• Injection site reactions including redness, swelling, and itching
• Potential for gallbladder events (cholelithiasis) with rapid weight loss, consistent with other GLP-1 class agents
• Heart rate increases of 2–4 bpm observed in some retatrutide trial participants

Safety Profile

Neither retatrutide nor cagrilintide is FDA-approved as of early 2025, making this blend an investigational combination. The individual components have shown acceptable safety profiles in Phase II trials, but long-term data is lacking. GI side effects are the primary tolerability concern and are managed through slow dose escalation. As with all GLP-1 class agents, there is a theoretical concern about medullary thyroid carcinoma based on rodent studies, though no human cases have been attributed to these drugs. Patients with a personal or family history of MTC or MEN2 should avoid this class. Pancreatitis risk has been flagged for GLP-1 agonists generally, though causation remains debated. Renal function should be monitored, as severe dehydration from GI side effects can impair kidney function. This blend should not be used during pregnancy, in patients with gastroparesis, or in those with a history of eating disorders where further appetite suppression could be harmful.

Week 1–2: Mild appetite reduction becomes noticeable, particularly around meal times. Some nausea is common, especially after larger meals. Week 3–4: Appetite suppression strengthens considerably as doses escalate. Most users report eating 30–50% less without conscious effort. Nausea typically peaks then begins to improve. Week 5–8: Weight loss becomes measurable, typically 3–6% of body weight. Energy levels stabilize. GI side effects generally diminish as the body adjusts. Week 9–16: Continued steady weight loss of 1–2 lbs per week. Many users report reduced cravings for high-calorie foods and improved relationship with portion sizes. Week 16+: Weight loss continues but rate may slow. Total weight loss at 6 months can reach 15–20%+ depending on dose and adherence. Body composition improvements become visible.

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