Semaglutide vs Tirzepatide: What Head-to-Head Data Show

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Side by side

Both are FDA-approved. Head-to-head trials have compared them on weight and blood sugar, not heart attacks. This page separates what has been compared directly from what has only been placed next to each other.

Key takeaways

• There are two head-to-head trials we found, both open-label and funded by Lilly, which makes tirzepatide. In 751 adults with obesity and no diabetes, SURMOUNT-5 found more weight loss with tirzepatide at 72 weeks (−20.2%) than with semaglutide (−13.7%). In 1,879 people with type 2 diabetes, SURPASS-2 found greater blood sugar reductions and weight loss with tirzepatide at 40 weeks.
• We found no trial comparing them directly on heart attacks, kidney disease or liver outcomes. Their heart trials used different comparators and different people.
• Their approved uses overlap but are not identical. Tirzepatide has a sleep apnea indication; semaglutide has indications for fatty liver disease (MASH) and kidney outcomes in type 2 diabetes.
• Both carry a boxed warning for thyroid C-cell tumors seen in rodents.
• “Better” depends on the goal and the person. That is a decision for a prescriber, using the label.

Which one causes more weight loss?

SURMOUNT-5 is the direct comparison on weight in people without diabetes. It was randomized and open-label, enrolled adults with obesity and no diabetes, and ran 72 weeks. Participants took the highest dose they tolerated.

Source: SURMOUNT-5. Three cautions:

1. Funding. The trial was sponsored by Lilly. That does not make the result wrong, but it is context.
2. What it measured. Weight and waist. It does not show that the extra weight loss translates into fewer heart attacks or other outcomes.
3. Open-label. Participants and investigators knew which drug was being taken.

In people with type 2 diabetes, SURPASS-2 (1,879 people, 40 weeks, open-label, funded by Lilly) tested three tirzepatide doses against one semaglutide dose. Tirzepatide lowered HbA1c more, by 0.15 to 0.45 percentage points depending on dose, and weight more, by 1.9 to 5.5 kg. Serious adverse events were reported in 5% to 7% of people on tirzepatide and 3% on semaglutide.

For reference, the placebo-controlled trials point the same direction: in STEP 1, semaglutide produced −14.9% vs −2.4% on placebo at 68 weeks; in SURMOUNT-1, tirzepatide produced −15.0% to −20.9% (depending on dose arm) vs −3.1% at 72 weeks. Those are different trials with different participants, so use SURMOUNT-5 for the comparison and these only as background.

What is each drug approved for?

✓ means the indication appears on the prescribing information we reviewed. — means we did not find it there.

Sources: labels for Wegovy, Ozempic, Zepbound and Mounjaro.

The cardiovascular rows hide a difference in who is covered. Wegovy’s indication is for adults with established cardiovascular disease and obesity or overweight. Mounjaro’s is for adults with type 2 diabetes at high cardiovascular risk. Mounjaro’s cardiovascular indication is new; we checked the label on Oct. 30, 2026.

Which is better for the heart?

We found no direct evidence. The heart trials answer different questions:

A reader might be tempted to say semaglutide’s hazard ratio looks stronger. That comparison is not valid: one trial used placebo, the other an active drug, and the populations differ. SURPASS-CVOT does not show that tirzepatide beats dulaglutide on heart outcomes, and no trial we reviewed compares tirzepatide with semaglutide on them.

Which one helps with sleep apnea, kidneys or the liver?

• Sleep apnea: tirzepatide has a randomized trial and an indication. In SURMOUNT-OSA (adults with moderate-to-severe apnea and obesity, 52 weeks), the apnea-hypopnea index fell by 25.3 events per hour vs 5.3 on placebo in people not using PAP therapy, and by 29.3 vs 5.5 in people using it.
• Kidneys: semaglutide’s FLOW trial (type 2 diabetes with chronic kidney disease) found a composite kidney outcome HR of 0.76 (0.66–0.88). We did not review a comparable tirzepatide trial.
• Liver: semaglutide’s phase 3 MASH trial improved fibrosis without worsening steatohepatitis in 36.8% vs 22.4%. Its approval is accelerated, so benefit on clinical outcomes remains to be confirmed. We did not review a comparable tirzepatide trial.

“We did not review” is a statement about our research, not proof that no such trial exists or that the other drug does not work.

How do the risks compare?

Both labels carry a boxed warning for thyroid C-cell tumors. Both are contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. The tumors were seen in rodents; relevance to humans has not been determined. Both labels also list severe gastrointestinal reactions, acute kidney injury from dehydration, gallbladder disease, pancreatitis, hypersensitivity, low blood sugar, diabetic retinopathy complications, and aspiration during anesthesia or deep sedation. The suicidal-ideation warning was removed from both in February 2026. The Zepbound label does not recommend combining tirzepatide with another GLP-1 product or another tirzepatide product.

Two things we cannot compare:

• Dropout from side effects. SELECT reported 16.6% vs 8.2% on placebo; SURMOUNT-1 reported 4.3–7.1% vs 2.6%. The populations and durations differ, so the rates are not comparable.
• Rare eye risk (NAION). Our review of observational studies covered semaglutide only. We did not evaluate tirzepatide data, so the absence of a finding here is not evidence of safety. See the semaglutide guide.

What about compounded versions?

Neither drug’s compounded versions are FDA-approved, and FDA does not review compounded drugs for safety, effectiveness or quality before marketing. As of Oct. 30, 2026:

• Neither is on FDA’s shortage list or the 503B list, and FDA proposed not adding either to the 503B list in May 2026. We found no final rule (FDA).
• A Sept. 18, 2026 FDA warning letter said a tirzepatide-plus-niacinamide product and others appear to be essentially copies of approved drugs. A warning letter is an agency position, not a court ruling.
• FDA has also warned about fraudulent products and adverse events, including doses above label amounts.

How to choose between them

The evidence does not crown one drug for everyone. A conversation with a prescriber can use the facts above:

• If the goal is weight loss without diabetes, SURMOUNT-5 favors tirzepatide on weight and waist.
• If a person has cardiovascular disease without diabetes, semaglutide has the placebo-controlled heart-event trial for that group.
• If sleep apnea is part of the picture, tirzepatide has the labeled indication.
• If fatty liver disease or kidney disease with type 2 diabetes is part of the picture, semaglutide has the relevant labeled indications.
• Tolerability, cost, insurance coverage and a person’s own history matter and are outside what these trials can answer.

Frequently asked questions

Is tirzepatide stronger than semaglutide?

For weight and waist in adults with obesity and no diabetes, one Lilly-funded, open-label 72-week trial found a larger effect with tirzepatide. A second Lilly-funded, open-label trial found larger blood sugar and weight effects in type 2 diabetes. “Stronger” is not established for other outcomes.

Is tirzepatide better for the heart?

Not shown. SURPASS-CVOT found tirzepatide non-inferior to dulaglutide, not superior, and we found no trial comparing it with semaglutide on heart outcomes.

Can you take both?

The Zepbound label does not recommend combining tirzepatide with another GLP-1 product. Ask your prescriber about your own situation.

Are compounded versions equivalent?

FDA says no. A compounded product is not an approved drug and has not been reviewed for safety, effectiveness or quality.

Related guides

• Semaglutide: Trial Evidence, Risks and Compounded Versions
• Tirzepatide: Trial Evidence, Risks and Compounded Versions
• Best Peptides for Weight Loss: What the Evidence Shows
• Tirzepatide vs Retatrutide: Approved vs Investigational

Sources we checked

1. SURMOUNT-5: tirzepatide vs semaglutide (PubMed)PubMed. Accessed October 30, 2026.
2. SURPASS-2: tirzepatide vs semaglutide in type 2 diabetes (PubMed)PubMed. Accessed October 30, 2026.
3. STEP 1 trial (PubMed)PubMed. Accessed October 30, 2026.
4. SURMOUNT-1 trial (PubMed)PubMed. Accessed October 30, 2026.
5. SELECT trial (PubMed)PubMed. Accessed October 30, 2026.
6. FLOW trial (PubMed)PubMed. Accessed October 30, 2026.
7. SURPASS-CVOT trial (PubMed)PubMed. Accessed October 30, 2026.
8. SURMOUNT-OSA trial (PubMed)PubMed. Accessed October 30, 2026.
9. Phase 3 trial of semaglutide in MASH (PubMed)PubMed. Accessed October 30, 2026.
10. Wegovy prescribing information (DailyMed, rev. 06/2026)FDA. Accessed October 30, 2026.
11. Ozempic prescribing information (DailyMed, rev. 01/2025)FDA. Accessed October 30, 2026.
12. Zepbound prescribing information (DailyMed, rev. 08/2026)FDA. Accessed October 30, 2026.
13. Mounjaro prescribing information (DailyMed)FDA. Accessed October 30, 2026.
14. FDA clarifies policies for compounders as national GLP-1 supply stabilizesFDA. Accessed October 30, 2026.
15. FDA's concerns with unapproved GLP-1 drugs used for weight lossFDA. Accessed October 30, 2026.
16. FDA warning letter to a compounding pharmacy, Sept. 18, 2026FDA. Accessed October 30, 2026.

Written and maintained by the Best Peptides For Editorial Team. How we rate evidence.