Semaglutide vs Tirzepatide: Receptors, Trials, and Label Warnings

How we built this table

The identity, regulatory, anti-doping, study-count and supplier rows come from our substance records, which list the approved brand products and their approval dates. The editorial rows were compiled from the US prescribing information for Ozempic ^{Source [1]} and Zepbound ^{Source [2]}, from the published reports of the trials named in the table, and from FDA pages, all checked on October 25, 2026. The comparison is informational. It is not a treatment recommendation, and it does not describe research listings.

One receptor or two

Semaglutide's label describes it as a GLP-1 analogue with 94% sequence homology to human GLP-1 that selectively binds to and activates the GLP-1 receptor. Its long action comes mainly from binding to albumin in the blood, made possible by a spacer and a fatty di-acid chain attached at one position, and a second change protects it from breakdown by the enzyme DPP-4. The peptide backbone is produced by yeast fermentation ^{Source [1]}.

Tirzepatide's label describes a single molecule, based on the sequence of the hormone GIP, that binds to and activates both the GIP and the GLP-1 receptors. It contains a C20 fatty diacid that enables albumin binding and prolongs its half-life ^{Source [2]}. So the two share a design idea, a hormone-like peptide that rides on albumin, but differ in which receptors they act on.

What the large trials measured

Each drug has a large placebo-controlled trial in adults with obesity or overweight and without diabetes. In STEP 1, 1,961 adults were followed for 68 weeks; mean body weight changed by -14.9% with semaglutide and -2.4% with placebo, and nausea and diarrhea were the most common adverse events ^{Source [3]}. In SURMOUNT-1, 2,539 adults were followed for 72 weeks; mean weight changed by -15.0%, -19.5% and -20.9% in three tirzepatide dose groups and by -3.1% with placebo, and the most common adverse events were gastrointestinal ^{Source [4]}.

These are separate trials with different durations, eligibility criteria and placebo groups. Their numbers show what each trial found; they are not a comparison of the two drugs. Our guide on how to read a peptide study explains why results from different trials should not be ranked against each other.

Head-to-head trials

Two trials compared the two drugs directly; at the time of SURPASS-2, tirzepatide was still an investigational drug. Both were open-label, meaning participants and investigators knew which drug was given, and both were funded by Eli Lilly, which makes tirzepatide.

• SURPASS-2 enrolled 1,879 people with type 2 diabetes for 40 weeks and compared three tirzepatide dose levels with one semaglutide dose level. All three tirzepatide groups lowered HbA1c, a measure of average blood sugar, more than semaglutide did, and body weight fell more with tirzepatide. Gastrointestinal events were the most common adverse events ^{Source [5]}.
• SURMOUNT-5 enrolled 751 adults with obesity and without type 2 diabetes for 72 weeks, each on the highest dose they tolerated. Mean weight changed by -20.2% with tirzepatide and -13.7% with semaglutide. Gastrointestinal events, mostly mild to moderate, were the most common adverse events in both groups ^{Source [6]}.

These trials answer a narrow question about specific products, populations and durations. They do not show which medicine suits a given person.

Label warnings

Both US labels open with the same boxed warning: risk of thyroid C-cell tumors ^{Source [1] Source [2]}. The most common adverse reactions listed for Ozempic are nausea, vomiting, diarrhea, abdominal pain and constipation ^{Source [1]}. For Zepbound, they begin with nausea, diarrhea, vomiting, constipation, abdominal pain and dyspepsia, and the label lists several more ^{Source [2]}. The two lists come from different trial populations, because Ozempic is approved for type 2 diabetes and Zepbound for weight management and sleep apnea, and both labels state that adverse reaction rates from one drug's trials cannot be directly compared with another's. Each label is the full source for its own product.

Research listings are not these medicines

Everything above describes the manufacturers' own products, as studied in their trials and as covered by FDA-approved labels. FDA has warned companies that sold semaglutide and tirzepatide labeled "for research purposes" or "not for human consumption" directly to consumers, and urges people not to buy them. It also says that semaglutide sodium and semaglutide acetate are different active ingredients from the one used in the approved drugs ^{Source [7]}.

Independent testing points the same way. In a 2024 study, researchers ordered semaglutide from illegal online pharmacies selling it without a prescription. Three vials arrived and none of the ordered pens did. The authors judged all three vials to be probable substandard and falsified products on visual inspection, and laboratory testing found endotoxin in every sample and purity far below the label claim ^{Source [8]}. For the legal categories involved, see approved, compounded and unapproved drugs and why availability is not approval.

What the table does not show

The table does not show how either medicine works for any individual, and it does not cover every approved use, trial or risk. We do not give dosing, preparation or usage guidance; questions about prescription medicines belong with a clinician. Research listings are not for personal use.