SURMOUNT-5: tirzepatide beat semaglutide for weight loss in the first head-to-head obesity trial

SURMOUNT-5 was a phase 3b, open-label trial sponsored by Eli Lilly, the maker of tirzepatide. It randomised 751 adults with obesity and no type 2 diabetes in a 1:1 ratio to one of the two drugs, each injected under the skin once a week for 72 weeks ^[1]. The registry entry lists the trial as completed in November 2024, with 751 people enrolled ^[2].

The primary end point was the percentage change in body weight from baseline to week 72. Using least-squares means, weight fell by 20.2% on tirzepatide (95% confidence interval 19.1% to 21.4%) and by 13.7% on semaglutide (12.6% to 14.9%). The difference was statistically significant (P<0.001) ^[1].

Waist circumference, a key secondary end point, fell by 18.4 cm on tirzepatide and 13.0 cm on semaglutide. People on tirzepatide were also more likely to reach each of the weight-loss thresholds the trial tested: at least 10%, 15%, 20% and 25% of starting weight ^[1]. The authors concluded that tirzepatide was superior to semaglutide for reducing body weight and waist circumference at 72 weeks in this population ^[1].

Each group received the maximum dose it could tolerate. For tirzepatide that was 10 mg or 15 mg once weekly; for semaglutide it was 1.7 mg or 2.4 mg once weekly ^[1]. All four are maintenance doses on the US weight-management labels. The current Zepbound label lists 5 mg, 10 mg or 15 mg weekly for weight reduction, with 15 mg as the maximum ^[3]. The current Wegovy injection label lists 1.7 mg or 2.4 mg weekly for weight reduction, with 2.4 mg recommended, and has since added a higher 7.2 mg option that was not part of SURMOUNT-5 ^[4].

These figures describe what the trial and the labels used. They are not guidance for anyone, and the doses on a licensed pen cannot be carried over to unlicensed vials. For unit and volume arithmetic in general, the peptide calculator explains the maths neutrally.

The most common adverse events in both groups were gastrointestinal, such as nausea, diarrhoea, constipation and vomiting. According to the published abstract, most were mild to moderate and happened mainly while the dose was being increased ^[1]. This is the same pattern seen in earlier trials of both drugs and reflected in the warnings sections of both US labels ^{[3] [4]}.

SURMOUNT-5 did not measure cardiovascular events, kidney outcomes or mortality, so it says nothing about whether one drug protects the heart better than the other. Its answer is limited to weight and waist size over 72 weeks.

Before SURMOUNT-5, the main direct comparison was SURPASS-2, a 40-week trial in 1,879 people with type 2 diabetes. It compared tirzepatide 5 mg, 10 mg and 15 mg with semaglutide 1 mg, a diabetes dose lower than the one used for weight management. All three tirzepatide doses lowered HbA1c more than semaglutide, and weight reductions were larger by 1.9 kg to 5.5 kg depending on dose ^[5]. Because semaglutide was tested at 1 mg, SURPASS-2 could not settle the obesity question. SURMOUNT-5 was designed to test tirzepatide vs semaglutide for weight loss directly, at weight-management doses, in people without diabetes.

There are limits. The trial was open-label, so participants and investigators knew which drug was given, and it was funded by the maker of one of the two drugs ^[1]. The population was adults with obesity and no diabetes, so the size of the gap may differ in people with diabetes or with lower body weight. Our tirzepatide vs semaglutide comparison sets SURMOUNT-5 alongside the separate placebo-controlled trials of each drug and their approved indications.

Among recent tirzepatide news and semaglutide news, SURMOUNT-5 is the most direct evidence on the search people make most often, "is tirzepatide better than semaglutide". For average weight loss over 72 weeks in adults with obesity and no diabetes, this trial found that it was, by about six and a half percentage points. It does not answer which drug suits a given person, which depends on medical history, tolerability and access.

Both drugs in this trial were licensed, pharmacy-grade medicines given in a monitored study. The results do not transfer to products sold online as research peptides, whose identity and dose are not verified. Regulators in several markets have warned about unlicensed GLP-1 products, and our legal status guide summarises the rules by country.

Our tirzepatide and semaglutide guides cover each drug's mechanism, full trial record and approved brand names in more depth, and the GLP-1 brand names guide explains which products contain which molecule.