PEPTIDEREPORT

Compound comparison

Semaglutide vs Tirzepatide for Weight Loss

Semaglutide (Wegovy, Novo Nordisk) and tirzepatide (Zepbound, Eli Lilly) are both FDA-approved for chronic weight management. Semaglutide is a GLP-1 receptor agonist whose STEP 1 trial demonstrated 14.9% mean weight loss at 68 weeks. Tirzepatide is a dual GIP/GLP-1 receptor agonist whose SURMOUNT-1 trial demonstrated 22.5% mean weight loss at 72 weeks. The SURMOUNT-5 head-to-head trial directly compared both drugs for obesity and reported greater weight loss with tirzepatide (approximately 20.9%) than semaglutide (approximately 17.3%) at 72 weeks. Both are available via telehealth platforms for their FDA-approved weight management indications. Cost, insurance coverage, and supply availability differ between the two. This page focuses specifically on the weight loss context and does not provide treatment guidance.

Last reviewed 2026-07-08 Next review 2026-08-07

At a glance

Attribute Semaglutide (Wegovy) Tirzepatide (Zepbound)
FDA-approved weight loss brand Wegovy (semaglutide 2.4 mg), approved June 2021 for chronic weight management Zepbound (tirzepatide), approved November 2023 for chronic weight management
Mechanism for weight loss GLP-1 receptor agonist only; reduces appetite and increases satiety through single incretin pathway Dual GIP and GLP-1 receptor agonist; reduces appetite through two incretin pathways, which may contribute to greater weight loss
Pivotal weight loss trial STEP 1 (Wilding et al., 2021, NEJM): 14.9% mean weight loss at 68 weeks SURMOUNT-1 (Jastreboff et al., 2022, NEJM): 22.5% mean weight loss at 72 weeks at the highest dose
Weight loss trial program STEP program (STEP 1 through STEP 8) — multiple Phase 3 trials across diverse populations including T2D, osteoarthritis, and international cohorts SURMOUNT program (SURMOUNT-1 through SURMOUNT-5) — Phase 3 trials including extended treatment (SURMOUNT-4) and head-to-head comparison (SURMOUNT-5)
Head-to-head weight loss trial (SURMOUNT-5) Approximately 17.3% mean weight loss at 72 weeks (semaglutide arm) Approximately 20.9% mean weight loss at 72 weeks (tirzepatide arm)
Cardiovascular outcomes in obesity SELECT trial (2023, NEJM) demonstrated reduced major adverse CV events in non-diabetic patients with obesity — completed and published Cardiovascular outcomes trials ongoing; no completed CVOT published in the obesity population as of last review
Route of administration Once-weekly subcutaneous injection (Wegovy); an oral formulation (Rybelsus) exists but is approved only for Type 2 diabetes, not weight management Once-weekly subcutaneous injection only (Zepbound); no oral formulation approved
Manufacturer Novo Nordisk Eli Lilly
Telehealth availability for weight loss Widely prescribed via telehealth platforms for chronic weight management under the Wegovy brand Widely prescribed via telehealth platforms for chronic weight management under the Zepbound brand
Cost and insurance coverage List price and insurance coverage vary; both branded products are expensive without coverage; Medicare Part D coverage has expanded for obesity treatment; prior authorization is commonly required List price and insurance coverage vary; both branded products are expensive without coverage; Medicare Part D coverage has expanded for obesity treatment; prior authorization is commonly required
Supply availability Has experienced periodic supply shortages due to high demand; FDA has tracked shortage status; compounded versions are not FDA-approved and subject to enforcement Has experienced high demand and supply constraints; compounded versions are not FDA-approved and subject to enforcement
Time on market for weight loss Approved since June 2021 — approximately 5 years of real-world use data Approved since November 2023 — approximately 2.5 years of real-world use data
Evidence level for weight loss Phase 3 trials (STEP program) + FDA approval + completed cardiovascular outcomes trial (SELECT) + head-to-head comparison (SURMOUNT-5 comparator arm) Phase 3 trials (SURMOUNT program) + FDA approval + head-to-head comparison (SURMOUNT-5) + cardiovascular outcomes trials ongoing

Semaglutide (Wegovy)

Open the Semaglutide evidence page

Semaglutide is a GLP-1 (glucagon-like peptide-1) receptor agonist developed by Novo Nordisk. For chronic weight management, it is marketed as Wegovy — a once-weekly subcutaneous injection approved by the FDA in June 2021. Ozempic, the same molecule at a lower indication, is approved for Type 2 diabetes but has been widely discussed off-label for weight loss. This comparison focuses on the Wegovy weight management indication.

The STEP (Semaglutide Treatment Effect in People with Obesity) trial program is the pivotal evidence base for semaglutide in weight management. STEP 1 (Wilding et al., 2021, NEJM) reported mean weight loss of 14.9% at 68 weeks with the 2.4 mg weekly formulation in adults with overweight or obesity. Multiple additional STEP trials (STEP 2 through STEP 8) studied semaglutide in various populations including patients with Type 2 diabetes, osteoarthritis, and different geographic cohorts, consistently showing substantial weight loss.

The SELECT cardiovascular outcomes trial (Ryan et al., 2023, NEJM) demonstrated that semaglutide reduced major adverse cardiovascular events in non-diabetic patients with obesity — an important finding for the weight management population, as cardiovascular risk is commonly elevated in this group. This gives semaglutide a more mature cardiovascular safety profile in the obesity context compared to tirzepatide, whose cardiovascular outcomes trials are ongoing.

Wegovy is widely prescribed through telehealth platforms and traditional healthcare providers for its FDA-approved chronic weight management indication. The drug has experienced periodic supply shortages, which have driven public discussion about compounded alternatives. Compounded semaglutide products are not FDA-approved and have been subject to FDA enforcement actions.

Tirzepatide (Zepbound)

Open the Tirzepatide evidence page

Tirzepatide is a dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptor agonist developed by Eli Lilly. For chronic weight management, it is marketed as Zepbound — a once-weekly subcutaneous injection approved by the FDA in November 2023. Mounjaro, the same molecule, is approved for Type 2 diabetes. This comparison focuses on the Zepbound weight management indication.

The SURMOUNT trial program is the pivotal evidence base for tirzepatide in weight management. SURMOUNT-1 (Jastreboff et al., 2022, NEJM) reported mean weight loss of 22.5% at 72 weeks at the highest dose in adults with obesity. SURMOUNT-4 evaluated extended treatment and demonstrated sustained weight loss over a longer treatment duration. These results positioned tirzepatide as the most effective approved weight loss pharmacotherapy at the time of publication.

The SURMOUNT-5 trial (Garvey et al., 2024, NEJM) was the pivotal head-to-head Phase 3 trial directly comparing tirzepatide to semaglutide for weight loss in adults with obesity. It reported greater mean weight loss with tirzepatide (approximately 20.9%) than with semaglutide (approximately 17.3%) at 72 weeks. This is the most direct comparative evidence available between the two drugs for the weight loss indication, though results are specific to the trial population and protocol.

Cardiovascular outcomes trials for tirzepatide are ongoing, meaning its cardiovascular safety data in the obesity population is less mature than semaglutide's. Zepbound is widely prescribed through telehealth platforms and traditional healthcare providers for its FDA-approved chronic weight management indication. Like semaglutide, tirzepatide has experienced high demand and periodic supply constraints.

Summary verdict

For the specific context of weight loss, both semaglutide (Wegovy) and tirzepatide (Zepbound) are FDA-approved for chronic weight management with robust Phase 3 trial evidence. The STEP 1 trial showed semaglutide achieving 14.9% mean weight loss at 68 weeks, while SURMOUNT-1 showed tirzepatide achieving 22.5% mean weight loss at 72 weeks. The SURMOUNT-5 head-to-head trial directly compared both drugs and reported greater weight loss with tirzepatide (approximately 20.9%) than semaglutide (approximately 17.3%) at 72 weeks, though these results are specific to the trial population and protocol. Semaglutide has a more mature cardiovascular outcomes evidence base in the obesity population (SELECT trial) and has been on the market longer. Tirzepatide's dual GIP/GLP-1 mechanism may contribute to its greater observed weight loss. Both drugs are available via telehealth for their FDA-approved weight management indications, with similar cost and access considerations. This comparison documents weight loss trial evidence and access differences; it does not recommend either drug or provide treatment guidance.

Related compounds: Semaglutide · Tirzepatide

Sources on this page

Source records are stored in the repo and linked from this comparison.

Tirzepatide and Semaglutide for Obesity in Adults (SURMOUNT-5)

New England Journal of Medicine · Peer reviewed · 2024-12-04 · accessed 2026-07-08

Head-to-head Phase 3 trial (Garvey et al., 2024) directly comparing tirzepatide and semaglutide for weight loss in adults with obesity. Reported greater mean weight loss with tirzepatide (approximately 20.9%) than semaglutide (approximately 17.3%) at 72 weeks.