GLP-1 Body Saturation Calculator
Calculate how long it takes for a GLP-1 receptor agonist to reach steady-state plasma concentration with repeated dosing, and understand the accumulation ratio for different peptides.
GLP-1 Body Saturation Calculator
Calculate steady-state accumulation and time to saturation for GLP-1 receptor agonists and related peptides with repeated dosing.
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GLP-1 agonist — Bioavailability: 89%
Results
Accumulation ratio
1.98x
Weeks to 90% steady state
3.3weeks
Weeks to 95% steady state
4.2weeks
Relative Plasma Concentration Over Time
View data table
| Week | % of Steady State |
|---|---|
| 0.0 | 50.6% |
| 0.5 | 35.6% |
| 1.0 | 75.6% |
| 1.5 | 53.1% |
| 2.0 | 88.0% |
| 2.5 | 61.8% |
| 3.0 | 94.1% |
| 3.5 | 66.1% |
| 4.0 | 97.1% |
| 4.5 | 68.2% |
| 5.0 | 98.6% |
| 5.5 | 69.2% |
| 6.0 | 99.3% |
| 6.5 | 69.8% |
| 7.0 | 99.6% |
| 7.5 | 70.0% |
| 8.0 | 99.8% |
| 8.5 | 70.1% |
| 9.0 | 99.9% |
| 9.5 | 70.2% |
| 10.0 | 100.0% |
| 10.5 | 70.2% |
| 11.0 | 100.0% |
| 11.5 | 70.3% |
| 12.0 | 100.0% |
How this was calculated
1. Elimination rate constant: ke = ln(2) / 165h = 0.00420 h-1
2. Accumulation ratio: R = 1 / (1 - e-ke×τ) = 1 / (1 - e-0.00420×168) = 1.98x
3. Time to 90% SS: t90 = ln(10) / ke = 548h (3.3 weeks)
4. Time to 95% SS: t95 = ln(20) / ke = 713h (4.2 weeks)
Half-life: 165 hours (6.9 days) | Dosing interval (τ): 168 hours
Time to Steady State
Semaglutide
Half-life: ~7 days (165h)
Steady state: ~4–5 weeks
Tirzepatide
Half-life: ~5 days (117h)
Steady state: ~3–4 weeks
Retatrutide
Half-life: ~6 days (144h)
Steady state: ~4 weeks
Accumulation Ratio Reference
| Peptide | t½ | Rac |
|---|---|---|
| Semaglutide | 165h | 2.07x |
| Tirzepatide | 117h | 1.60x |
| Retatrutide | 144h | 1.84x |
| Cagrilintide | 180h | 2.18x |
| Mazdutide | 184h | 2.21x |
Rac = peak steady-state level relative to a single dose, with weekly dosing.
Why This Matters
- 1Dose titration schedules are designed to gradually approach steady state and minimize GI side effects.
- 2Full clinical effects are not seen until steady state is reached, which takes 4–5 half-lives.
- 3Higher accumulation ratios mean more drug is present at steady state relative to the first dose.
- 4Washout after discontinuation also takes 4–5 half-lives (about the same time as reaching steady state).
Understanding Steady-State Pharmacokinetics
When a medication is taken repeatedly at fixed intervals, the drug accumulates in the body until the amount eliminated between doses equals the amount administered. This equilibrium is called steady state. For GLP-1 receptor agonists, which have remarkably long half-lives (5 to 8 days), achieving steady state takes several weeks of consistent dosing.
The time to reach steady state depends solely on the drug's elimination half-life, not on the dose or dosing frequency. It takes approximately 4 to 5 half-lives to reach 90–95% of steady state. For semaglutide with a half-life of about 7 days, this means approximately 4–5 weeks. For tirzepatide with a 5-day half-life, it is approximately 3–4 weeks.
The Accumulation Ratio
The accumulation ratio (Rac) describes how much higher the peak plasma concentration is at steady state compared to after a single dose. It is determined by the ratio of half-life to dosing interval. A drug with a half-life equal to its dosing interval will have an accumulation ratio of approximately 2x, meaning steady-state peak levels are double those seen after the first dose.
For weekly-dosed GLP-1 agonists:
- Semaglutide (t½ ≈ 7 days): Rac ≈ 2.1x. Peak levels at steady state are about twice those after the first injection.
- Tirzepatide (t½ ≈ 5 days): Rac ≈ 1.6x. Less accumulation because more drug is cleared between weekly doses.
- Cagrilintide (t½ ≈ 7.5 days): Rac ≈ 2.2x. Slightly more accumulation than semaglutide.
Clinical Implications for Dose Titration
Dose titration schedules for GLP-1 agonists are carefully designed to account for accumulation kinetics. Starting at a low dose and gradually increasing over weeks allows the body to adapt to rising drug levels, reducing the incidence and severity of gastrointestinal side effects such as nausea.
For example, the semaglutide (Ozempic/Wegovy) titration schedule starts at 0.25 mg weekly for 4 weeks, then increases to 0.5 mg for another 4 weeks, and continues escalating every 4 weeks. The 4-week intervals align with the time needed to approach steady state at each dose level before increasing.
Skipping titration steps or increasing doses too rapidly can lead to disproportionately higher drug levels (due to incomplete clearance of the previous dose) and increased side effects.
Formula Reference
ke = ln(2) / t½
Rac = 1 / (1 - e-ke × τ)
t90% = ln(10) / ke ≈ 3.32 × t½
fss(n) = 1 - e-n × ke × τ
References
- Kapitza C, et al. Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive pill. J Clin Pharmacol. 2015;55(5):497-504. PMID: 25475122
- Overgaard RV, et al. Clinical pharmacokinetics of oral semaglutide: analyses of data from clinical pharmacology trials. Clin Pharmacokinet. 2021;60(10):1335-1348. PMID: 33969456
- Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. PMID: 35658024
- Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity. N Engl J Med. 2023;389(6):514-526. PMID: 37366315
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Medical Disclaimer
This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.