Semaglutide vs. Tirzepatide: What’s the Difference?

Brand names and approved uses

How they work

Both drugs mimic gut hormones called incretins, which are released after eating.

Semaglutide is a GLP-1 receptor agonist. GLP-1 increases insulin when blood sugar is high, reduces glucagon, slows stomach emptying, and reduces appetite through the brain.

Tirzepatide is a dual GIP and GLP-1 receptor agonist. It does everything semaglutide does through GLP-1, and adds GIP receptor activity. GIP also boosts insulin after meals and appears to influence how fat tissue stores and releases energy. The combination is thought to explain tirzepatide’s larger effect on weight, although the exact contribution of GIP is still being studied.

Weight loss: the head-to-head trial

SURMOUNT-5 is the only direct comparison for weight management. It randomized 751 adults with obesity or overweight, without diabetes, to the highest tolerated dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks.

In separate trials, STEP 1 reported 14.9% weight loss with semaglutide 2.4 mg at 68 weeks, and SURMOUNT-1 reported 20.9% with tirzepatide 15 mg at 72 weeks.

Blood sugar: the head-to-head trial

SURPASS-2 compared tirzepatide with semaglutide 1 mg in 1,879 adults with type 2 diabetes over 40 weeks. All three tirzepatide doses lowered A1c more than semaglutide.

One caveat: semaglutide is now approved up to 2 mg for diabetes, and the trial used 1 mg.

Heart and kidney protection

Semaglutide has the longer track record here.

• In SELECT, semaglutide 2.4 mg reduced major adverse cardiovascular events by 20% in adults with cardiovascular disease and obesity but no diabetes. Wegovy is approved to reduce cardiovascular risk.
• In FLOW, semaglutide 1 mg slowed kidney disease progression in people with type 2 diabetes and chronic kidney disease. Ozempic is approved for that use.

Tirzepatide’s cardiovascular outcomes trial, SURPASS-CVOT, compared it against dulaglutide (another GLP-1 drug) in people with type 2 diabetes and cardiovascular disease and found it was not inferior. The FDA approved Mounjaro to reduce cardiovascular risk in adults with type 2 diabetes on August 28, 2026. Zepbound is approved for moderate to severe obstructive sleep apnea in adults with obesity, based on the SURMOUNT-OSA trials.

Side effects

The side-effect profiles are similar because both drugs act on GLP-1.

Common: nausea, diarrhea, vomiting, constipation, abdominal pain, and reduced appetite, most often during dose increases.

Warnings on both labels: boxed warning for thyroid C-cell tumors seen in rodents (do not use with a personal or family history of medullary thyroid carcinoma or MEN 2), pancreatitis, gallbladder disease, low blood sugar when combined with insulin or sulfonylureas, kidney injury from dehydration, and delayed stomach emptying that can affect other medicines.

In SURMOUNT-5, discontinuation because of side effects was 6.1% for tirzepatide and 8.0% for semaglutide. In SURPASS-2, gastrointestinal side effects were similar between the two drugs.

Dosing schedules

Semaglutide (Wegovy injection): The label starts at a low dose and raises the dose in steps every 4 weeks; see the semaglutide calculator’s label-dose table for the steps. The Wegovy label also lists a 7.2 mg dose; who it is for is set out in the label. Ozempic for diabetes has a separate label.

Tirzepatide (Zepbound and Mounjaro): The labels start at low doses and raise the dose in steps every 4 weeks; see the tirzepatide calculator’s label-dose table for the steps.

Both are injected under the skin. The semaglutide labels list the abdomen, thigh, or upper arm. The tirzepatide labels list the abdomen or thigh, with the back of the upper arm only when another person gives the injection. Each brand comes in several pens, syringes, or vials, and the strength per mL differs between them.

Half-life and missed doses

Semaglutide’s half-life is about 1 week. Tirzepatide’s is about 5 days. Semaglutide reaches steady levels after 4 to 5 weeks of weekly dosing, and tirzepatide after about 4 weeks. Each label’s missed-dose rules are in the injection sites guide, so the prescribing information for the specific product is the reference.

Which one is right for a given person?

That is a prescribing decision. Factors a clinician weighs include diabetes status, cardiovascular history, kidney function, the amount of weight loss needed, side-effect tolerance, insurance coverage, and cost. Tirzepatide produces more weight loss on average. Semaglutide has more outcome data. Insurance coverage varies by plan, so check yours.