Comparison guide / Semaglutide vs Tirzepatide

Semaglutide vs Tirzepatide: What the Head-to-Head Trials Show.

Updated October 2026 · 8 minute read

Semaglutide and tirzepatide are the two most widely discussed incretin-based medicines. Two published randomised trials have compared them directly. This guide explains how they differ and what those trials actually found.

Research information only. This article summarises published research. It is not medical advice, a dosing guide, or a recommendation of either medicine. Trial averages do not predict an individual outcome, and approved medicines are available only through licensed prescribers and pharmacies.

01 / Short answer

The short answer

In the two head-to-head trials published so far, tirzepatide produced greater average reductions in body weight than semaglutide. In SURPASS-2 (type 2 diabetes), it also produced greater reductions in HbA1c, a measure of long-term blood sugar.[1]

SURPASS-2 was a 40-week Phase 3 trial registered as NCT03987919 that randomised 1,879 adults with type 2 diabetes on metformin. Both trials were open-label and funded by Eli Lilly, tirzepatide's manufacturer.[2]

"Greater average reduction" is a statement about groups in a controlled trial. It does not mean one medicine is right for any particular person; that depends on clinical factors only a licensed clinician can assess.

View the Tirzepatide research listing

02 / Mechanism

How do they differ?

Semaglutide is a selective GLP-1 receptor agonist: it activates one receptor involved in glucose-dependent insulin release, satiety, and gastric emptying. Tirzepatide is a dual agonist that activates both the GLP-1 receptor and the GIP receptor.[4]

Both are given as once-weekly injections in their main approved forms. Semaglutide is also available as an oral tablet in some indications. The trials compared maximum-tolerated or fixed weekly injectable doses.[5]

Adding GIP activity is the main pharmacological difference. How much of tirzepatide's larger average effect comes from GIP signalling, versus dose and other factors, is still studied and should not be treated as settled.

03 / Published evidence

What did the head-to-head trials find?

SURPASS-2 (NEJM, 2021): over 40 weeks, mean HbA1c change was −2.01, −2.24 and −2.30 percentage points with tirzepatide 5, 10 and 15 mg, versus −1.86 with semaglutide 1 mg. Tirzepatide was non-inferior and superior at all doses. Estimated treatment differences in body weight versus semaglutide were −1.9 kg, −3.6 kg and −5.5 kg.[2]

SURMOUNT-5 (NEJM, 2025) randomised 751 adults with obesity but without type 2 diabetes to the maximum tolerated dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks. Mean weight change was −20.2% with tirzepatide versus −13.7% with semaglutide; waist circumference change was −18.4 cm versus −13.0 cm.[3]

Participants on tirzepatide in SURMOUNT-5 were more likely to reach weight reductions of at least 10%, 15%, 20% and 25%. Lilly's announcement reported 64.6% reaching at least 15% weight loss with tirzepatide versus 40.1% with semaglutide. Both trials were sponsor-funded and open-label, meaning participants knew which medicine they received.[4]

Shop Tirzepatide pen

04 / Safety evidence

How do side effects compare?

In both trials the most common adverse events with both medicines were gastrointestinal and mostly mild to moderate. In SURPASS-2, nausea occurred in 17–22% of tirzepatide groups versus 18% with semaglutide, and diarrhea in 13–16% versus 12%.[4]

In SURMOUNT-5, gastrointestinal events occurred mainly during dose escalation in both groups. Neither trial established a clear overall tolerability advantage for one medicine.[3]

Both approved medicines carry boxed warnings about thyroid C-cell tumours seen in rodent studies, along with other warnings in their official prescribing information. Anyone considering either should rely on that information and a licensed clinician.

05 / Regulators

Approval status

Both molecules are approved in the US and EU under specific brand names and indications: semaglutide as Ozempic and Wegovy, tirzepatide as Mounjaro and Zepbound. Approval covers those assessed products only. The FDA has separately published concerns about unapproved and compounded GLP-1 products.[3]

In the UAE, the Emirates Drug Establishment maintains the public registered medical product directory. Approved medicines are dispensed through licensed channels. Afiya Labs research listings are laboratory reference materials, not these approved medicines.[6]

06 / Quick answers

Frequently asked questions

Which produces more weight loss, semaglutide or tirzepatide?

In SURMOUNT-5, the head-to-head obesity trial, mean weight change at 72 weeks was −20.2% with tirzepatide versus −13.7% with semaglutide. These are group averages; individual responses vary widely.

What is the main difference between them?

Semaglutide activates only the GLP-1 receptor. Tirzepatide activates both GLP-1 and GIP receptors.

Are the side effects different?

Both mainly cause gastrointestinal effects such as nausea and diarrhea, mostly mild to moderate and concentrated during dose escalation. Rates were broadly similar in the head-to-head trials.

Who funded the head-to-head trials?

Both SURPASS-2 and SURMOUNT-5 were funded by Eli Lilly, which makes tirzepatide. Both were open-label.

Are Afiya Labs listings the same as Ozempic or Mounjaro?

No. Afiya Labs research listings are laboratory reference materials, not the approved branded medicines, and are not presented as suitable for human use.

07 / Sources