Retatrutide titration calculator
Calculate your retatrutide titration schedule based on Phase 3 trial protocol. Includes glucagon receptor warnings, ketone prediction, and NAFLD hepatic data.
Retatrutide is a triple GIP, GLP-1, and glucagon receptor agonist currently in Phase 3 clinical trials. It represents the next generation of incretin-based therapies, adding glucagon receptor co-agonism to the dual GIP/GLP-1 mechanism of tirzepatide. Phase 3 data shows a mean body weight reduction of 24.9% at 96 weeks with no plateau — the highest efficacy ever demonstrated by a pharmacological agent for obesity.
The glucagon receptor component is the key mechanistic difference. Glucagon receptor activation drives the liver to switch fuel sources — preferentially oxidizing stored fat rather than dietary carbohydrate. This generates a measurable increase in ketone body production (2-3× baseline in Phase 2 data), confirming the metabolic switch is active. It also drives superior hepatic fat clearance: 86% liver fat reduction in the Phase 2 NAFLD sub-study, and 93% of participants reaching normal liver fat levels.
This calculator implements the Phase 3 TRIUMPH-1 escalation protocol: 1mg → 2mg → 4mg → 8mg → 12mg, with a minimum of 4 weeks at each level. The slower ramp compared to tirzepatide reflects the more variable tolerability profile associated with glucagon receptor activation. Gastrointestinal adverse events occur in approximately 72% of participants, with 6.8% discontinuing due to tolerability.
This tool is for research purposes only. The NAFLD flag activates hepatic fat clearance projections. Ketone predictions are based on Phase 2 metabolic data. Retatrutide is not FDA-approved.
Triple agonist — GIP + GLP-1 + Glucagon
Retatrutide's glucagon receptor activation produces stronger fat oxidation than tirzepatide but also more variable tolerability. The calculator accounts for glucagon-specific effects including paresthesia risk and ketone elevation.
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18–24.9 lbs
18% (4mg) to 25% (12mg) · Phase 3 data
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Minimal ketone elevation expected at initiation dose
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Week 1 of 4 at 1mg. Continue current dose. Next escalation assessment at week 5.
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Frequently asked questions
What makes retatrutide more effective than tirzepatide for weight loss?+
Retatrutide activates three hormone receptors — GIP, GLP-1, and glucagon — while tirzepatide activates only GIP and GLP-1. The glucagon receptor component increases energy expenditure through hepatic fat oxidation and brown adipose tissue thermogenesis, counteracting the metabolic adaptation (reduced energy expenditure) that limits weight loss with dual agonists. Phase 3 data shows 24.9% weight loss vs approximately 22.5% with tirzepatide.
Why does retatrutide cause tingling and numbness?+
Paresthesia (tingling and numbness, typically in hands and feet) was reported in 12.5% of Phase 3 participants at the 12mg dose. This side effect is not observed with tirzepatide or semaglutide and is attributed to glucagon receptor activation affecting peripheral nerve function. It is generally mild and reversible. Researchers should document and monitor any paresthesia symptoms.
What does the NAFLD flag do in the retatrutide calculator?+
When enabled, the NAFLD flag activates hepatic fat clearance projections based on the Phase 2 sub-study data. Retatrutide showed 86% liver fat clearance at therapeutic doses (≥4mg), driven by glucagon receptor activation increasing hepatic fat oxidation. The flag also shows fibrosis stage guidance from the sub-study and notes that hepatic effects begin at the 4mg dose level.
How long does the full retatrutide escalation take?+
Following the Phase 3 protocol with successful escalation at each 4-week checkpoint: 1mg (4 weeks) → 2mg (4 weeks) → 4mg (4 weeks) → 8mg (4 weeks) → 12mg. Total time to maximum dose is approximately 16 weeks. Some researchers stay at 4mg or 8mg based on tolerability and weight loss trajectory.
Is retatrutide available for research use?+
Retatrutide (LY3437943) is currently in Phase 3 trials and is not FDA-approved. It is available through licensed research chemical suppliers as an investigational compound. Eli Lilly is expected to file for FDA approval in late 2026, with a potential decision in late 2027.
Research background
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Jastreboff AM, Kaplan LM, Frías JP, et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial title: . New England Journal of Medicine. DOI: 10.1056/NEJMoa2301972
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