Semaglutide vs Tirzepatide: The Two FDA Labels Side by Side

The number of receptors each one activates. Semaglutide is a GLP-1 analogue that activates the GLP-1 receptor. Tirzepatide is a single peptide that activates both the GIP and GLP-1 receptors. Both are once-weekly injections with the same boxed warning, but they are different molecules with separate approvals and separate trial data behind each label.

In one head-to-head trial, SURMOUNT-5, yes on its primary endpoint. Results posted to ClinicalTrials.gov show a mean body-weight change of -20.2% on tirzepatide and -13.7% on semaglutide at week 72. The trial enrolled 751 adults with obesity or overweight. The limits matter as much as the numbers. It was open-label and sponsored by Eli Lilly, which makes tirzepatide. It measured weight change, not every outcome a prescriber weighs. It is one trial, not a verdict.

Broadly similar ones. Both labels list nausea, diarrhoea, vomiting and constipation as the most common adverse reactions, and both carry a boxed warning for thyroid C-cell tumours in rodents. The exact rates differ between the labels, but they come from different trial programmes with different placebo rates, so comparing the percentages directly is not reliable.

Both labels say no. The Wegovy label states that co-administration with any other GLP-1 receptor agonist is not recommended, and the Zepbound label says the same. Tirzepatide activates the GLP-1 receptor, so combining the two falls under that instruction.

No. FDA has documented dosing errors, counterfeit product and fraudulent labelling in the compounded and grey-market supply of both drugs, and unapproved salt forms substituted for semaglutide. As of 31 May 2026 FDA had received 990 adverse event reports tied to compounded semaglutide and more than 730 tied to compounded tirzepatide.

Because of what its label allows that tirzepatide's does not. Only semaglutide, as Ozempic, carries an FDA indication for reducing kidney decline, kidney failure and cardiovascular death in adults with type 2 diabetes and chronic kidney disease. Tirzepatide has no equivalent kidney indication. Semaglutide is also the only one of the two available as a once-daily tablet (Rybelsus), for someone who cannot or will not inject. Beyond the label, the choice depends on a person's other conditions and how they tolerated a prior GLP-1 medicine. It also depends on which drug their insurer covers for their diagnosis. That is a prescriber's decision, not a fact this page can rank.

Two things its label flags directly. The first is insulin or insulin secretagogues such as sulfonylureas. Combining either with semaglutide raises the risk of hypoglycaemia, and the label says to consider lowering the dose of the other medicine. The second is other GLP-1 receptor agonists, including tirzepatide. Co-administration is not recommended. Semaglutide also delays gastric emptying, which can affect how well oral medicines are absorbed. The label calls for monitoring any oral drug taken alongside it.

There is no fixed timeline, and the trials behind tirzepatide's approval were not designed to answer it. The Zepbound label reports percentage change in body weight at 72 weeks, not weeks to a set number of pounds. A 20 lb loss is a different fraction of starting weight for every person. Dosing also starts low and steps up over the first months by label design, so early weight loss is typically slower than later in treatment. Only a prescriber tracking a person's own weight can say how quickly that person responds.

No published trial has isolated a cause for that, and the two drugs' side-effect tables cannot be read against each other to explain it. Tirzepatide activates a receptor, GIP, that semaglutide does not, which is a real pharmacological difference. But the gastrointestinal side-effect rates on each label come from separate trial programmes with different placebo rates. A lower number on one label is not proof that the drug causes less sickness for everyone. If one drug suits a person better than the other, discuss it with the prescriber who can see their history. This page cannot explain it in general.

The same ones any GLP-1-based medicine carries, plus a few specific to it. Its label carries the same boxed warning for thyroid C-cell tumours as semaglutide's. It also carries the same class of warnings for pancreatitis, gallbladder disease, acute kidney injury, hypoglycaemia and hypersensitivity. Specific to tirzepatide: it has no oral tablet option (semaglutide does, as Rybelsus). It is not FDA-approved for chronic kidney disease (semaglutide, as Ozempic, is). Its injection comes in six dose strengths against semaglutide's five, which is one more titration step to reach the top dose. Its most common adverse reactions are gastrointestinal, at the rates in the tables on this page.

The labels cannot tell you. Nausea was 44% on Wegovy 2.4 mg against 16% on placebo, and 28% on Zepbound 15 mg against 8% on placebo. Those figures come from separate trials with different placebo rates, so they are not a head-to-head result. The one direct comparison, SURMOUNT-5, was designed to measure weight change, not to settle tolerability.