GLP-1 reference

Tirzepatide vs Semaglutide: A Research-Framed Comparison

By Baris Bingor · Last updated June 12, 2026

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. Peptly's 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. Peptly's Semaglutide profile supports both schedules — switch in the protocol picker.

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. Peptly's slider shows the unit count for every step as you adjust BAC volume — pick the volume that keeps the maintenance dose in the readable 10-80 unit range.

How to use Peptly with either molecule

Open Peptly and pick the profile. Tap Semaglutide or Tirzepatide. The profile loads with the standard reconstitution math and titration schedule.
Enter vial mass and BAC water. Set the vial size (e.g., 10 mg) and the bacteriostatic water you added (e.g., 2 ml or 3 ml). Concentration auto-computes.
Slide through titration steps. Tap the step (0.25 mg, 0.5 mg, etc. for Semaglutide; 2.5 mg, 5 mg, etc. for Tirzepatide). Peptly displays exact draw volume + visual syringe mark.
Save the protocol. Save the vial × BAC × current step. The tracker logs each weekly shot, prompts site rotation, and reloads the math next week in one tap.

What Peptly does NOT do

Recommend a dose. The schedules above are FDA-approved labels; your protocol may differ.
Diagnose or treat any condition. Peptly is a calculator + log.
Send your dose log to any server. Everything stays on-device.
Suggest which molecule to use. That's between you and your clinician.

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. Peptly supplies the reconstitution math — not the clinical data.

Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5, head-to-head) — N Engl J Med, 2025.
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2, head-to-head) — N Engl J Med, 2021.
Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1) — N Engl J Med, 2022.
Titration steps and maintenance doses are from the FDA-approved prescribing information for Wegovy, Ozempic, Mounjaro, and Zepbound (Drugs@FDA).

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. Peptly defaults to 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; Peptly's slider lets you preview the unit count as you adjust BAC.

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. Peptly's Retatrutide profile uses the same reconstitution math as the other two; you set your own target dose based on the research literature you're following.

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? +

Peptly computes the reconstitution math, displays the exact U-100 syringe draw, and logs each dose. It does not prescribe doses or schedules — those come from the FDA labels or your research protocol. Peptly removes the arithmetic so you don't mis-convert mg ↔ mcg ↔ units ↔ ml during weekly shots.

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