# Tirzepatide vs Semaglutide: Which Works Better for Weight Loss? | This GLP

In the randomized SURMOUNT-5 trial, weight fell 20.2% on tirzepatide and 13.7% on semaglutide at 72 weeks | routine-care studies found a three-to-four-point gap.

Publisher: This GLP Editorial Team
Canonical: https://thisglp.com/research/tirzepatide-vs-semaglutide-which-works-better
Updated: 2026-09-18
Published: 2026-09-17

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Evidence

# Tirzepatide vs Semaglutide: Which Works Better for Weight Loss?

In a 72-week randomized trial at weight-management doses, weight fell 20.2 percent on tirzepatide and 13.7 percent on semaglutide. Routine-care studies found a smaller gap, three to four points.

[This GLP Editorial Team](https://thisglp.com/about)September 20268 min readUpdated September 2026

Weight loss, tirzepatide against semaglutide · chart review, 12 mo · −16.6% · −13.4% · matched cohort, 2 yr · −14.7% · −10.8% · Randomized, SURMOUNT-5: 20.2% against 13.7% at 72 weeks.

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## Key takeaways

-   In SURMOUNT-5, a randomized trial at weight-management doses, weight fell 20.2% on tirzepatide and 13.7% on semaglutide over 72 weeks.
-   Participants knew which drug they took, and Eli Lilly, tirzepatide's maker, paid for the trial.
-   A 511-patient chart review found 16.6% against 13.4% at twelve months; a matched cohort found 14.7% against 10.8% over two years.
-   An earlier randomized trial, SURPASS-2, compared them in type 2 diabetes against semaglutide 1 mg, the diabetes dose.
-   Previous obesity medication blunted both drugs, but semaglutide far more: 14.4% down to 10.4%, against 17.1% down to 16.1%.

Tirzepatide, on current evidence. In SURMOUNT-5, a randomized trial at weight-management doses, weight fell 20.2% on tirzepatide and 13.7% on semaglutide over 72 weeks [\[5\]](https://thisglp.com/research/tirzepatide-vs-semaglutide-which-works-better#ref-5). Participants knew which drug they were on, and the sponsor was Eli Lilly, tirzepatide's manufacturer. Routine-care studies point the same way, by three to four percentage points.

## The randomized comparisons, and their limits

SURMOUNT-5 randomized 751 adults with obesity but without type 2 diabetes [\[5\]](https://thisglp.com/research/tirzepatide-vs-semaglutide-which-works-better#ref-5). Each took the maximum tolerated dose of one drug: tirzepatide 10 or 15 mg, or semaglutide 1.7 or 2.4 mg, weekly for 72 weeks. Weight fell 20.2% (95% CI −21.4 to −19.1) against 13.7% (−14.9 to −12.6). Waists shrank by 18.4 cm on tirzepatide and 13.0 cm on semaglutide.

Two limits sit beside that result. Participants knew which drug they were taking, and the sponsor makes one of them. Gastrointestinal events were the most common adverse events in both arms, mostly mild to moderate and mostly during dose escalation.

An earlier trial compared them in type 2 diabetes. SURPASS-2 randomized people with type 2 diabetes to tirzepatide at 5, 10 or 15 mg, or semaglutide at 1 mg [\[1\]](https://thisglp.com/research/tirzepatide-vs-semaglutide-which-works-better#ref-1). HbA1c fell 2.01, 2.24 and 2.30 points against 1.86, and weight differed by 1.9 kg, 3.6 kg and 5.5 kg.

The comparator matters. Semaglutide 1 mg is the diabetes dose; weight management uses 2.4 mg. A reader setting the SURPASS-2 figures beside the STEP trials is comparing different doses — the mismatch this site keeps finding, set out in [the tirzepatide network comparison](https://thisglp.com/research/is-tirzepatide-better-than-dulaglutide).

## What routine practice shows

Two observational comparisons, neither randomized.
| Study | Tirzepatide | Semaglutide | Design |
| --- | --- | --- | --- |
| Chart review, 511 patients, 12 months | 16.6% | 13.4% | Retrospective, multicenter |
| Matched cohort, 2 years | 14.7% | 10.8% | Propensity-matched records |
| Reached ≥15% (chart review) | 56.8% | 40.7% | — |
| Reached ≥15% in year 1 (cohort) | 42.6% | 21.6% | — |

Two observational comparisons, neither randomized. Multicenter chart review and a propensity-matched cohort

The matched cohort also measured pace: 2.54% of body weight a month against 2.18% [\[4\]](https://thisglp.com/research/tirzepatide-vs-semaglutide-which-works-better#ref-4). Among patients without diabetes in the chart review, the gap widened to 18.5% against 14.2% [\[2\]](https://thisglp.com/research/tirzepatide-vs-semaglutide-which-works-better#ref-2).

A third and much larger matched cohort points the same way. Among 18,386 propensity-matched adults in routine US care, tirzepatide was significantly more likely to reach every weight-loss threshold [\[3\]](https://thisglp.com/research/tirzepatide-vs-semaglutide-which-works-better#ref-3). It also recorded something the smaller studies do not: follow-up ended in discontinuation for 55.9% of the tirzepatide group and 52.5% of the semaglutide group. More than half of each arm stopped.

## The finding most likely to change a decision

Previous obesity medication blunted one drug far more than the other

Patients who had used an obesity medication before did worse on both, but unevenly: semaglutide fell from 14.4% to 10.4%, a loss of four points, while tirzepatide fell from 17.1% to 16.1%, a loss of one. If that holds up, treatment history should inform which drug comes next — and it currently does not.

## Side effects: the direction is unusual, the evidence is weak

The chart review recorded gastrointestinal side effects in 28.5% of tirzepatide patients against 50.7% on semaglutide, which runs against the usual pattern where the stronger drug is harder to tolerate.

Read how that was collected. In a randomized trial, adverse events are solicited from everyone on a schedule; in a chart review they appear when a patient raised them and a clinician wrote them down. The cohort study reached a similar conclusion using AI curation of clinical notes, a method it reports no validation for here.

So the tolerability claim is directionally interesting and weakly evidenced. It sits against the network meta-analysis pattern in [the drugs that lose most and are tolerated worst](https://thisglp.com/research/the-best-losers-are-the-worst-tolerated).

## Who responded, and who did not

The two-year matched cohort reports a demographic pattern it does not explain. Women were over-represented among high responders for both drugs, as were White patients. Black and Hispanic patients were over-represented among the group losing less than 5%.

The paper offers no mechanism and this site will not invent one. It is a description of who did well in the records examined. It is also the kind of finding that ought to shape who future trials enroll — a representativeness problem this site set out in [who actually gets into trials](https://thisglp.com/research/are-glp1-drugs-safe-for-older-adults).

What none of this prices. Which of the two is cheaper depends entirely on the seller, and the stopping question applies to both — see [what happens when you stop tirzepatide](https://thisglp.com/research/what-happens-when-you-stop-tirzepatide).

## Frequently asked

Which works better, tirzepatide or semaglutide?

Tirzepatide. In the randomized SURMOUNT-5 trial, weight fell 20.2% on tirzepatide and 13.7% on semaglutide over 72 weeks. In routine care the gap was three to four points: 16.6% against 13.4% in one study, 14.7% against 10.8% in another.

Has anyone compared them in a randomized trial?

Yes. SURMOUNT-5 randomized 751 adults with obesity but without type 2 diabetes to the maximum tolerated dose of each drug for 72 weeks: 20.2% weight loss on tirzepatide against 13.7% on semaglutide. Both groups knew their assigned drug, and Eli Lilly, which sells tirzepatide, sponsored it. SURPASS-2 compared them earlier in type 2 diabetes, against the 1 mg diabetes dose of semaglutide.

Does it matter if I have taken a weight drug before?

It appeared to, unevenly. Prior obesity medication dropped semaglutide results from 14.4% to 10.4% but tirzepatide only from 17.1% to 16.1%.

Which causes more side effects?

A chart review recorded gastrointestinal effects in 28.5% of tirzepatide patients against 50.7% on semaglutide. Those were chart-reported rather than systematically collected, which limits how much the difference can carry.

## Sources

1.  \[1\] Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK (2021). Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes The New England Journal of Medicine. [PMID 34170647](https://pubmed.ncbi.nlm.nih.gov/34170647/)
2.  \[2\] Ghusn W, Fansa S, Tama E, Anazco D, Espinosa MA, Villamarin J (2026). Real-World Comparative Effectiveness of Tirzepatide and Semaglutide for Obesity: A Multicentered Study Mayo Clinic Proceedings. [PMID 42383938](https://pubmed.ncbi.nlm.nih.gov/42383938/)
3.  \[3\] Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, Brar R, Baker C, Gluckman TJ (2024). Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity JAMA Internal Medicine. [PMID 38976257](https://pubmed.ncbi.nlm.nih.gov/38976257/)
4.  \[4\] Venkatakrishnan AJ, Murugadoss K, Soundararajan V (2026). Weight-loss dynamics with tirzepatide versus semaglutide PNAS Nexus. [PMID 42311474](https://pubmed.ncbi.nlm.nih.gov/42311474/)
5.  \[5\] Aronne LJ, et al. (2025). Tirzepatide as Compared with Semaglutide for the Treatment of Obesity The New England Journal of Medicine. [PMID 40353578](https://pubmed.ncbi.nlm.nih.gov/40353578/)

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