Semaglutide vs Tirzepatide: FDA status and research

	Semaglutide	Tirzepatide
FDA status	FDA approved. First U.S. approval 2017. Sold as Ozempic, Rybelsus and Wegovy ^{[1, 2, 3]}	FDA approved. First U.S. approval 2022. Sold as Mounjaro and Zepbound ^{[4, 5]}
Studied for	Labeled for type 2 diabetes, weight reduction, heart risk reduction and MASH liver disease ^{[1, 2]}	Labeled for type 2 diabetes, heart risk in type 2 diabetes, weight reduction and sleep apnea with obesity ^{[4, 5]}
Route	Under the skin once weekly, or tablets by mouth once daily ^{[1, 2, 3]}	Under the skin once weekly ^{[4, 5]}
Key trials	STEP 1 (weight), SELECT (heart events), SUSTAIN-6 ^{[8, 16, 17]}	SURMOUNT-1 (weight), SURPASS-2 and SURMOUNT-5 (both vs semaglutide) ^{[9, 7, 6]}
Receptors	GLP-1 receptor ^[1]	GIP and GLP-1 receptors ^[4]
Half-life	About 1 week (label) ^[1]	About 5 days (label) ^[4]
Shortage	FDA declared the shortage resolved on Feb 21, 2025 ^[10]	FDA declared the shortage resolved on Oct 2, 2024 and again on Dec 19, 2024 ^[10]
503B bulks list	FDA proposed in 2026 not to include it. No final decision found as of Oct 25, 2026 ^{[12, 13]}	Same proposal and status as semaglutide ^{[12, 13]}
WADA	Not prohibited. Monitored in the 2026 Monitoring Program ^{[14, 15]}	Not prohibited. Monitored in the 2026 Monitoring Program ^{[14, 15]}

Semaglutide and tirzepatide are both FDA-approved weekly shots for type 2 diabetes and weight. The main difference is the target. Semaglutide acts on one gut hormone receptor, GLP-1 ^[1]. Tirzepatide acts on two, GIP and GLP-1 ^[4]. In the SURMOUNT-5 head-to-head trial in adults with obesity, weight fell 20.2% with tirzepatide and 13.7% with semaglutide over 72 weeks ^[6].

How they differ in design

Semaglutide is a copy of the gut hormone GLP-1 with a fatty side chain. The Ozempic label says it shares 94% of its sequence with human GLP-1 ^[1]. The label gives a half-life of about one week ^[1].

Tirzepatide is one peptide built on the GIP sequence. The Mounjaro label calls it a GIP receptor and GLP-1 receptor agonist ^[4]. It is a chain of 39 amino acids ^[18]. The label gives a half-life of about 5 days ^[4]. Both drugs are given once a week, and the long half-life is what allows this ^{[1, 4]}.

Approved uses and forms

Semaglutide comes as shots (Ozempic, Wegovy) and as daily tablets (Rybelsus, and Ozempic and Wegovy tablets) ^{[1, 2, 3]}. Wegovy is labeled for weight reduction, heart risk reduction in people with obesity or overweight, and a liver disease called MASH ^[2].

Tirzepatide comes only as a weekly shot ^{[4, 5]}. Mounjaro is labeled for type 2 diabetes and for lowering heart risk in adults with type 2 diabetes ^[4]. Zepbound is labeled for weight reduction and for obstructive sleep apnea in adults with obesity ^[5]. See the full semaglutide and tirzepatide pages for label details.

Head-to-head trials

Two trials compared the drugs directly. SURPASS-2 enrolled 1,879 adults with type 2 diabetes for 40 weeks. A1c fell 2.01 to 2.30 points with tirzepatide 5, 10 or 15 mg, and 1.86 points with semaglutide 1 mg ^[7].

SURMOUNT-5 enrolled 751 adults with obesity but without type 2 diabetes. It was an open-label phase 3b trial. People got the highest dose they could tolerate of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) once weekly for 72 weeks ^[6]. Weight fell 20.2% with tirzepatide and 13.7% with semaglutide. In both groups, the most common side effects were stomach related and mostly mild to moderate ^[6]. The trial was funded by the maker of tirzepatide ^[6].

Separate placebo trials found similar patterns. In STEP 1, semaglutide 2.4 mg lowered weight 14.9% vs 2.4% with placebo over 68 weeks ^[8]. In SURMOUNT-1, tirzepatide lowered weight 15.0% to 20.9% vs 3.1% with placebo over 72 weeks ^[9]. These trials had different people, so their numbers should not be compared directly ^{[8, 9]}.

Safety

Both labels carry a boxed warning for thyroid C-cell tumors seen in rodents. Neither should be used by people with a personal or family history of medullary thyroid cancer or MEN 2 ^{[1, 4]}. The most common side effects on both labels are stomach related, such as nausea, diarrhea, vomiting and constipation ^{[1, 4]}.

Compounding and the law

FDA has ended the shortages of both drugs. That closed the main legal path for mass compounding of copies ^[10]. FDA has received reports of adverse events tied to compounded versions of both drugs, and it warns that compounded products are not reviewed for safety or quality ^[11]. On April 30, 2026, FDA announced a proposal to keep both off the 503B bulks list. The Federal Register notice followed on May 1, 2026 ^{[12, 13]}. See the FDA Peptide Status Tracker for current status.

Neither drug is on the WADA 2026 Prohibited List. WADA tracks markers of both in its 2026 Monitoring Program ^{[14, 15]}.

Frequently asked questions

Is tirzepatide stronger than semaglutide?

In SURMOUNT-5, weight fell 20.2% with tirzepatide and 13.7% with semaglutide over 72 weeks in adults with obesity without diabetes ^[6].

What is the difference between semaglutide and tirzepatide?

Semaglutide acts on the GLP-1 receptor. Tirzepatide acts on both the GIP and GLP-1 receptors ^{[1, 4]}.

Are both semaglutide and tirzepatide FDA approved?

Yes. Semaglutide was first approved in 2017 and tirzepatide in 2022 ^{[1, 4]}.

Is there a tirzepatide pill?

No approved tirzepatide pill is on the current labels. Tirzepatide is labeled as a weekly shot ^{[4, 5]}. Semaglutide has approved tablets ^[3].

Which lasts longer in the body?

Semaglutide has a half-life of about 1 week. Tirzepatide has a half-life of about 5 days ^{[1, 4]}.

Can semaglutide or tirzepatide still be compounded?

FDA ended both shortages. FDA does not plan to act on a pharmacy that fills four or fewer copies of either drug in a month ^[10].