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The medicines

Semaglutide vs tirzepatide

They are the two most prescribed weight-management medicines, and they are often compared on social media with more confidence than evidence. There is now a head-to-head trial, which helps. It answers one question well — average weight loss — and leaves the question that matters most to you for your prescriber.

By the Cafeity teamUpdated 3 min read

The short answer

Semaglutide acts on the GLP-1 receptor; tirzepatide acts on both the GLP-1 and GIP receptors. In SURMOUNT-5, a head-to-head trial in 751 adults with obesity but without diabetes, average weight change at 72 weeks was −20.2% on tirzepatide and −13.7% on semaglutide, each at the highest dose tolerated.1 Both have mostly gastrointestinal side effects, most common during dose increases. Semaglutide is weekly or a daily tablet with a half-life of about a week; tirzepatide is weekly with a half-life of about 5–6 days.23 Which suits you depends on your health, other conditions, tolerability, cost and coverage — a decision for your prescriber.

Bar chart from the SURMOUNT-5 head-to-head trial: average weight change at 72 weeks of minus 20.2% on tirzepatide and minus 13.7% on semaglutide.
SURMOUNT-5 (open-label, 751 adults with obesity without type 2 diabetes, maximum tolerated doses). Averages, not predictions.

How they differ

From the US prescribing information for each medicine.
SemaglutideTirzepatide
ReceptorsGLP-1GLP-1 and GIP
FormsWeekly injection; daily tabletWeekly injection
Half-lifeAbout 1 weekAbout 5–6 days
Peak after injection1 to 3 daysMedian about 24 hours
Weight-management approvalYesYes (also obstructive sleep apnoea with obesity)

Sources: prescribing information.23

The head-to-head trial

SURMOUNT-5 randomised 751 adults with obesity and without type 2 diabetes to the maximum tolerated dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg), weekly, for 72 weeks. Average weight change was −20.2% with tirzepatide and −13.7% with semaglutide, and tirzepatide also reduced waist circumference more.1 The trial was open-label (participants knew which medicine they had) and funded by tirzepatide's manufacturer — worth knowing, though the primary outcome is an objective measurement.

Separate placebo-controlled trials point the same way: semaglutide 2.4 mg produced −14.9% over 68 weeks in STEP 1, and tirzepatide 15 mg −20.9% over 72 weeks in SURMOUNT-1 — though comparing across different trials is less reliable than a head-to-head.45

Side effects

Most common reactions in the weight-management trials, from each label. Different trials, so not a direct comparison.
ReactionSemaglutide 2.4 mg (placebo)Tirzepatide 5–15 mg (placebo)
Nausea44% (16%)25–29% (8%)
Diarrhoea30% (16%)19–23% (8%)
Vomiting24% (6%)8–13% (2%)
Constipation24% (11%)11–17% (5%)
Hair loss3% (1%)4–5% (1%)

Sources: prescribing information.23 The labels warn that rates from different medicines' trials cannot be compared directly.

Choosing between them

The average result is one input. Others your prescriber will weigh include your other conditions (some indications are specific to one medicine), how you tolerate side effects, other medicines you take — tirzepatide, for example, can make birth control pills less reliable for a period after starting and after each increase — whether you would prefer a tablet, and cost and coverage.3 Switching from one to the other is a clinical decision with its own instructions; this site does not give dose conversions.

Common questions

Is tirzepatide better than semaglutide?
For average weight loss in adults with obesity without diabetes, the SURMOUNT-5 trial found more with tirzepatide (−20.2% against −13.7% at 72 weeks).1 "Better" for a person depends on much more than the average; ask your prescriber.
Which has more side effects?
Both are mainly gastrointestinal. Their labels come from different trials, and the labels say rates cannot be compared directly.23
Can I switch from semaglutide to tirzepatide?
Switching is a decision for your prescriber, who will set the starting dose. Cafeity does not provide dose conversions.

Sources

  1. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5) Aronne LJ et al. New England Journal of Medicine 2025
  2. Semaglutide injection and tablets for weight management — US prescribing information DailyMed, US National Library of Medicine, version published 30 June 2026
  3. Tirzepatide injection for weight management and obstructive sleep apnoea — US prescribing information DailyMed, US National Library of Medicine, version published 2 September 2026
  4. Once-weekly semaglutide in adults with overweight or obesity (STEP 1) Wilding JPH et al. New England Journal of Medicine 2021;384:989–1002
  5. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1) Jastreboff AM et al. New England Journal of Medicine 2022;387:205–216

Written by the Cafeity team from the sources listed here. Figures from prescribing information are quoted as the label states them; trial results are averages from those trials, not predictions for any one person. This page has not yet been reviewed by a clinician — see the editorial policy for how pages are researched and corrected.