GLP-1 reference

Tirzepatide vs Semaglutide: A Research-Framed Comparison

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What's the difference between Tirzepatide and Semaglutide?

Semaglutide is a GLP-1 receptor agonist (single receptor). Tirzepatide is a GLP-1 + GIP dual receptor agonist. Both are once-weekly subcutaneous peptides. Semaglutide titrates 0.25 → 2.4 mg/wk over 16 weeks (Wegovy schedule); Tirzepatide titrates 2.5 → 15 mg/wk over 20 weeks (Mounjaro / Zepbound schedule). Clinical trial data shows Tirzepatide at maintenance produces larger weight loss on average, but they're not interchangeable mg-for-mg. The reconstitution math is the same formula for both — concentration = vial mass ÷ BAC water; draw volume = dose ÷ concentration.

At a glance

Field Semaglutide Tirzepatide
Class GLP-1 receptor agonist GLP-1 + GIP dual receptor agonist
Cadence Once weekly Once weekly
Maintenance dose (weight management) 2.4 mg/wk 15 mg/wk (max)
Starting dose 0.25 mg/wk 2.5 mg/wk
Titration steps 5 steps over 16 weeks (0.25 → 0.5 → 1 → 1.7 → 2.4 mg) 6 steps over 20 weeks (2.5 → 5 → 7.5 → 10 → 12.5 → 15 mg)
Common research vial sizes 5 mg, 10 mg lyophilized 10 mg, 15 mg lyophilized
Concentration math sensitivity Doses span 0.25 → 2.4 mg (10× range) Doses span 2.5 → 15 mg (6× range)

Semaglutide titration (Wegovy schedule)

FDA-approved 16-week step-up for weight management:

  • Weeks 1-4: 0.25 mg/wk
  • Weeks 5-8: 0.5 mg/wk
  • Weeks 9-12: 1.0 mg/wk
  • Weeks 13-16: 1.7 mg/wk
  • Week 17+: 2.4 mg/wk (maintenance)

Ozempic (Type 2 diabetes label) titrates the same molecule differently: 0.25 → 0.5 → 1.0 → optional 2.0 mg.

Tirzepatide titration (Mounjaro / Zepbound schedule)

FDA-approved 20-week step-up. The longer ramp + higher maintenance reflects Tirzepatide's dual receptor profile:

  • Weeks 1-4: 2.5 mg/wk
  • Weeks 5-8: 5 mg/wk
  • Weeks 9-12: 7.5 mg/wk (optional)
  • Weeks 13-16: 10 mg/wk
  • Weeks 17-20: 12.5 mg/wk (optional)
  • Week 21+: 15 mg/wk (maintenance, max)

Reconstitution math is identical for both

The same three-step formula works for both molecules:

  • Concentration (mg/ml) = vial mass (mg) ÷ BAC water (ml)
  • Draw volume (ml) = target dose (mg) ÷ concentration (mg/ml)
  • U-100 units = draw volume × 100

The difference shows up in how the concentration choice scales:

  • Semaglutide 5 mg vial + 2 ml BAC = 2.5 mg/ml. A 0.25 mg dose = 0.1 ml = 10 units. A 2.4 mg maintenance dose = 0.96 ml = 96 units (close to syringe max — most researchers use 5 mg + 1 ml = 5 mg/ml so maintenance is 48 units).
  • Tirzepatide 10 mg vial + 2 ml BAC = 5 mg/ml. A 2.5 mg start dose = 0.5 ml = 50 units. A 15 mg maintenance dose = 3 ml = 300 units (needs three syringe pulls — most researchers use a 10 mg + 1 ml = 10 mg/ml concentration so maintenance is 150 units split across two draws).

The right concentration depends on which dose you'll be at longest. The free calculator on this site shows the unit count for any amount as you change the water volume — pick the volume that keeps the maintenance dose in the readable 10-80 unit range.

Working out the units for either molecule

  1. Confirm the vial mass. Read the label. Research vials are commonly 5 mg or 10 mg for Semaglutide and 10 mg or 15 mg for Tirzepatide.

  2. Work out the concentration. Divide the vial mass by the bacteriostatic water you added (e.g., 10 mg ÷ 2 ml = 5 mg/ml).

  3. Work out the draw. Divide the amount from your prescription or protocol by the concentration to get ml, then multiply by 100 for U-100 units. The free calculator on this site does it for the numbers you type and draws the line on a syringe.

What Peptly does NOT do

  • Recommend a dose. The schedules above are FDA-approved labels; your protocol may differ.
  • Calculate or suggest an amount in the app. Every amount in your log is one you typed.
  • Diagnose or treat any condition. Peptly is a reference site and a log.
  • Send your log to any server. Your log stays on your phone.
  • Suggest which molecule to use. That's between you and your clinician.

See also

Primary sources

The weight-loss comparisons and titration schedules on this page trace to the pivotal clinical trials (New England Journal of Medicine) and the FDA-approved prescribing information. The calculator on this site supplies the reconstitution math — not the clinical data.

Frequently asked questions

Is Tirzepatide stronger than Semaglutide milligram-for-milligram? +

They aren't directly comparable on a per-mg basis because they hit different receptors. Tirzepatide is a dual GLP-1 + GIP agonist; Semaglutide is GLP-1 only. Published clinical trials (SURPASS for Tirzepatide; STEP for Semaglutide) show Tirzepatide at its maintenance dose (15 mg/wk) produces larger average weight loss than Semaglutide at its maintenance dose (2.4 mg/wk for Wegovy), but the doses themselves are not interchangeable.

Can I use the same syringe size for both? +

Yes — both are typically drawn with a U-100 insulin syringe at the same reconstitution conventions, and the calculator on this site uses U-100. The unit count per dose differs because of concentration: a Tirzepatide 15 mg dose draws more units than a Semaglutide 2.4 mg dose, even at the same mg/ml concentration.

Does Tirzepatide need a higher BAC water volume because of the larger dose? +

Not necessarily. The choice of BAC water volume sets the concentration. For Tirzepatide at 10 mg vial + 2 ml BAC = 5 mg/ml, a 5 mg dose is 1 ml = 100 units on a U-100 syringe (the full barrel). Most research protocols pick a BAC volume that lands the dose in the 10-80 unit range; the free calculator on this site shows the unit count as you change the water volume.

How does Retatrutide compare to Tirzepatide and Semaglutide? +

Retatrutide is a triple agonist — GLP-1, GIP, AND glucagon. Phase 2 clinical data shows it producing larger weight loss than either Tirzepatide or Semaglutide. It is still in late-stage trials and has no FDA-approved dosing schedule yet. The reconstitution math is the same as for the other two.

Why do the titration schedules differ? +

Each is a separate FDA-approved schedule designed to minimize GI side effects (nausea, vomiting) during dose ramp. Semaglutide steps every 4 weeks; Tirzepatide also steps every 4 weeks but starts higher and runs longer. The schedules aren't arbitrary — they're based on tolerability data from clinical trials.

Can I switch between Tirzepatide and Semaglutide research protocols? +

Researchers do switch protocols, but the dosing isn't a direct conversion. There's no validated "equivalence" table because the drugs hit different receptors. Most protocols treat them as separate titrations — finish or pause one, then start the other from the manufacturer's starting dose. Always consult primary literature.

How long is each stable after reconstitution? +

Most research protocols refrigerate reconstituted Semaglutide and Tirzepatide at 2-8 °C and use within 4-6 weeks when reconstituted with bacteriostatic water. Stability varies by source peptide and storage conditions. Consult primary literature or a licensed clinician for stability data specific to your protocol.

Where does Peptly fit in? +

In two separate places. The free calculator on this site does the reconstitution math for the numbers you type, so you don't mis-convert mg ↔ mcg ↔ units ↔ ml. The Peptly app is a private log: it keeps each entry with the amount exactly as you typed it, reminds you on your own schedule and suggests your next injection site; for semaglutide and tirzepatide, Peptly Pro also draws an estimated level chart from your own log and published half-lives, labelled "Estimated, not measured". Neither prescribes doses or schedules — those come from the FDA labels, your prescriber or your research protocol.

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