GLP-1 Playbook

The GLP-1 Peptide Protocol

Exact dosing schedules, titration guide, and cycle structure for Semaglutide, Tirzepatide, and Retatrutide. Use the quiz below to find your starting compound, then read through the full protocols.

Compound Selector

Which compound is right for you?

Answer 5 quick questions to get your personalized recommendation.

Question 1 of 50%

What is your primary goal?

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The golden rule: Only escalate your dose when you have been at the current dose for the full period AND you are tolerating it well. Never escalate to manage a plateau if you are still experiencing side effects.

Protocols

All Three Compounds

Semaglutide

Most Researched

GLP-1 Receptor Agonist

Starting dose

0.25 mg

Once weekly

Semaglutide is the most extensively studied GLP-1 agonist with the longest clinical track record. It is the right starting point for first-time users, those with GI sensitivity, and anyone prioritizing a well-documented safety profile. The key rule: if you are still losing weight at your current dose, do not increase it. Many users achieve their goals at 0.25-0.5 mg and never need to go higher.

Strengths

  • +Longest clinical research history of any GLP-1 compound
  • +Well-understood side effect profile and management
  • +Lower cost than Tirzepatide and Retatrutide
  • +Effective for metabolic health beyond weight loss

Considerations

  • !Single receptor action -- less potent than dual/triple agonists
  • !Weight loss ceiling typically lower than Tirzepatide or Retatrutide

Titration Schedule

WeekDoseNotes
Wk 1–40.25 mgFoundation phase. Do not escalate early -- many users lose significant weight here and stay at this dose for months.
Wk 5–80.5 mgOnly increase if weight loss has stalled for 2+ weeks AND you are tolerating 0.25 mg well with no significant side effects.
Wk 9–121.0 mgOnly escalate if plateau continues. Many users find their sweet spot at 0.5 mg and stay there long-term.
Wk 13–161.5 mgHigh-end dose. Only escalate if still plateaued and tolerating 1.0 mg without significant side effects.
Wk 17+2.0 mgMaximum dose for most protocols. Only reach this if lower doses are genuinely insufficient after adequate time at each tier.

Tirzepatide

Dual Action

GLP-1 + GIP Dual Agonist

Starting dose

2.5 mg

Once weekly

Tirzepatide acts on both GLP-1 and GIP receptors, producing greater average weight loss than Semaglutide in head-to-head research. Best for users who have plateaued on Semaglutide or who want stronger metabolic effects from the start. Important: some users lose significant weight at 2.5 mg and never need to escalate. Always use the lowest effective dose.

Strengths

  • +Dual receptor action produces greater average weight loss than Semaglutide
  • +Strong appetite suppression with additional GIP-mediated metabolic benefits
  • +Effective for body recomposition alongside fat loss
  • +Well-documented in large-scale clinical trials (SURMOUNT series)

Considerations

  • !Higher cost than Semaglutide
  • !Acts as a diuretic for most users -- electrolyte management (sodium, potassium, magnesium) is important
  • !Not recommended as a first compound for highly GI-sensitive users

Titration Schedule

WeekDoseNotes
Wk 1–42.5 mgFoundation phase. Many users lose 3-5% body weight here without ever escalating. Do not rush past this dose.
Wk 5–85 mgOnly increase if weight loss has stalled for 2+ weeks AND you are tolerating 2.5 mg well. Ensure electrolytes are adequate before escalating.
Wk 9–127.5 mgMid-range dose. Only escalate if plateau continues. Nausea risk increases with each step -- do not rush.
Wk 13–1610 mgEscalate only if still plateaued after 4+ weeks at 7.5 mg. Most users do not need to go beyond this point.
Wk 17–2012.5 mgHigh-end dose. Only if well tolerated and lower doses are genuinely insufficient.
Wk 21+15 mgMaximum dose. Most users do not need to reach this level.

Retatrutide

Triple Action

GLP-1 + GIP + Glucagon Triple Agonist

Starting dose

0.5 mg

Once weekly

Retatrutide is the most potent GLP-1-class compound currently in research, acting on three receptors simultaneously. Phase 2 trials showed the highest average weight loss of any compound in this class. Critical: Retatrutide accumulates in the body over weeks -- effects at week 3 are significantly stronger than week 1 at the same dose. The clinical trial starting dose of 2 mg is too high for most people. Community consensus is to start at 0.5 mg.

Strengths

  • +Highest average weight loss of any GLP-1-class compound in Phase 2 research
  • +Triple receptor action: GLP-1 + GIP + glucagon
  • +Strong energy expenditure increase via glucagon receptor activation
  • +Promising results for metabolic syndrome and NAFLD

Considerations

  • !Less long-term data than Semaglutide or Tirzepatide
  • !Accumulates over weeks -- do not judge efficacy in the first 7 days
  • !Unique side effect: skin sensitivity (allodynia) -- clothes may feel uncomfortable at higher doses
  • !Not recommended for first-time GLP-1 users. Start with Semaglutide first.

Titration Schedule

WeekDoseNotes
Wk 1–40.5 mgFoundation phase. Do not judge results yet -- the compound is still building up. Many users feel strong appetite suppression by week 3 at this dose without ever needing to escalate.
Wk 5–81.0 mgOnly increase if you are still experiencing significant hunger / food noise AND tolerating 0.5 mg well. If appetite is already suppressed, stay here.
Wk 9–122.0 mgOnly escalate if genuinely plateaued. This is where most users find their long-term therapeutic dose. Do not rush past this point.
Wk 13–164.0 mgExperienced users only. Only escalate if plateau has persisted for 4+ weeks at 2 mg. Skin sensitivity side effects become more common at this dose.
Wk 17–206.0 mgHigh-end dose. Only for experienced users who have tolerated all previous tiers without significant side effects.
Wk 21+8.0 mgMaximum practical dose for most users. The Phase 2 trial maximum of 12 mg is rarely needed and carries substantially higher side effect risk.

Injection Timing (All Compounds)

Inject on the same day each week. Evening injections (6–9 PM) are recommended so that peak plasma levels occur overnight, minimizing nausea during waking hours. Subcutaneous injection into the abdomen, outer thigh, or upper arm. Rotate sites weekly.

Adjustment Guide

How to Respond to What You Feel

Your body will give you signals. This guide tells you exactly what to do with them. Tap any symptom to expand.

Compound Comparison

Semaglutide vs Tirzepatide vs Retatrutide

SemaglutideTirzepatideRetatrutide
Receptor targetsGLP-1GLP-1 + GIPGLP-1 + GIP + Glucagon
Avg. weight loss (trials)~15%~20%~24%
Starting dose0.25 mg2.5 mg0.5 mg
Max dose2 mg15 mg8 mg*
Best for beginners✓—✗
Research maturityHighHighMedium
Relative cost$$$$$$

* Retatrutide Phase 2 trials studied doses up to 12 mg, but the community-recommended practical maximum is 8 mg. Most users achieve their goals between 2-4 mg. Start at 0.5 mg regardless of prior GLP-1 experience.

Research purposes only. This protocol is for educational and research purposes. Peptides are research chemicals. Consult a qualified healthcare provider before beginning any peptide protocol, especially if you have pre-existing medical conditions or are taking other medications.