Zepbound vs. Wegovy: The Head-to-Head Results Are In — And They're Clear
If you've been weighing your options between tirzepatide (Zepbound) and semaglutide (Wegovy) for weight loss, you no longer have to wonder which one works better. For the first time, scientists put both medications head-to-head in a rigorous clinical trial — and in May 2025, the results were published in the New England Journal of Medicine, the most respected medical journal in the world.[1]
Here in Shreveport and across northwest Louisiana, where nearly 40% of adults are living with obesity, this study matters. It gives physicians and patients a clear, evidence-based answer to one of the most common questions in weight management today.
What Was the SURMOUNT-5 Trial?
The SURMOUNT-5 trial was a Phase 3b, randomized, head-to-head study — the gold standard of clinical research design. Researchers randomly assigned 751 adults with obesity (but without type 2 diabetes) to receive either tirzepatide or semaglutide once a week by injection for 72 weeks — that's about 17 months.
Both groups received the maximum tolerated dose of their medication:
- Tirzepatide group: 10 mg or 15 mg weekly (Zepbound)
- Semaglutide group: 1.7 mg or 2.4 mg weekly (Wegovy)
Participants had a BMI of 30 or higher, or a BMI of 27 or higher with at least one weight-related health condition. The trial ran at 32 sites across the United States and Puerto Rico, and was led by Dr. Louis J. Aronne, Director of the Comprehensive Weight Control Center at Weill Cornell Medicine — one of the leading obesity researchers in the country.
The Results: Tirzepatide Wins — By a Significant Margin
At 72 weeks, the results were unambiguous:
- Tirzepatide: average body weight loss of −20.2%
- Semaglutide: average body weight loss of −13.7%
That gap — 6.5 percentage points — is not a small difference. For a 250-pound person, that's the difference between losing about 34 pounds (semaglutide) and about 50 pounds (tirzepatide). In absolute terms, tirzepatide patients lost an average of 22.8 kg (50 lbs), while semaglutide patients lost 15.0 kg (33 lbs).[1]
The secondary results were just as striking. Here's how the two groups compared on reaching key weight loss milestones:
| Weight loss milestone | Tirzepatide | Semaglutide |
|---|---|---|
| Lost ≥10% of body weight | 81.6% | 60.5% |
| Lost ≥15% of body weight | 64.6% | 40.1% |
| Lost ≥20% of body weight | 48.4% | 27.3% |
| Lost ≥25% of body weight | 31.6% | 16.1% |
Waist circumference also shrank more with tirzepatide: an average of 18.4 cm (about 7 inches) compared to 13.0 cm (about 5 inches) with semaglutide.[1]
"The SURMOUNT-5 head-to-head results demonstrated tirzepatide led to greater weight reduction compared to semaglutide," said Dr. Aronne, "providing further evidence to support tirzepatide as an effective option for obesity management."[2]
Why Does Tirzepatide Produce More Weight Loss?
Both medications work by mimicking hormones your gut naturally produces after a meal — hormones that tell your brain you're full and help regulate blood sugar. The difference is in how many receptors they activate.
Semaglutide activates one receptor: the GLP-1 (glucagon-like peptide-1) receptor.
Tirzepatide activates two receptors: GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). That second receptor appears to add an extra layer of appetite suppression and fat-burning that semaglutide can't provide on its own. Think of it as a two-key system versus a one-key system — both work, but tirzepatide unlocks more doors.
What About Side Effects?
Both medications share a similar side effect profile — primarily nausea, stomach upset, constipation, and occasional vomiting, especially during the early weeks when the dose is being increased.
One important finding from SURMOUNT-5: tirzepatide was actually better tolerated in this trial. Gastrointestinal side effects caused 5.6% of semaglutide patients to stop their medication entirely, compared to only 2.7% of tirzepatide patients.[1] That's roughly half the dropout rate due to GI issues.
The trial also found that men lost about 6% less weight than women on both medications. This is a meaningful finding for male patients — not because the medications don't work, but because it helps set realistic expectations.
Does This Mean Everyone Should Choose Tirzepatide?
Not necessarily — and this is where physician-led care matters.
Tirzepatide produces more weight loss on average, and the data is now clear. But the "right" medication depends on your full medical picture:
- Insurance coverage and cost — Wegovy may be covered when Zepbound is not, or vice versa. Your physician can help you navigate this.
- Cardiovascular history — Semaglutide has extensive cardiovascular outcome data, including the SELECT trial showing a 20% reduction in heart attacks and strokes in people with obesity.
- Tolerance — Some patients do better on one medication than the other. Individual response varies.
- Contraindications — Both medications have specific medical conditions that rule them out.
At Shreveport Direct Care, Dr. Bass reviews your full health history before recommending any weight loss medication. We don't hand out prescriptions without labs, a real exam, and a plan. Our physician-led weight loss program is built into your membership — starting at $109 per month — so the conversations happen at every visit, not just at the start.
Tirzepatide versus Semaglutide
What This Means for Patients in Shreveport and the Ark-La-Tex
Louisiana consistently ranks among the top three states in the country for obesity prevalence. Our region also carries one of the highest burdens of cardiovascular disease, type 2 diabetes, and related conditions in the South. For our patients, the availability of highly effective, FDA-approved weight loss medications — and a physician who can match the right one to your needs — is genuinely life-changing.
SURMOUNT-5 doesn't end the conversation about which medication to use. But it does give us the clearest head-to-head data we've ever had — and it shows that the gap between tirzepatide and semaglutide is real, meaningful, and reproducible under controlled conditions.
If you've been thinking about starting a weight loss program, or you've tried medication before and didn't get the results you hoped for, this research is worth a conversation with your doctor.
Ready to find the right weight loss plan for you? Schedule a free meet-and-greet with Dr. Bass at Shreveport Direct Care. We'll review your health history, talk through your options — including whether tirzepatide, semaglutide, or another approach is the right fit — and build a plan that's actually designed for your life.
📞 318-588-7060 | ✉️ info@shreveportdirectcare.com
FAQs
1. What is the SURMOUNT-5 trial? SURMOUNT-5 is a Phase 3b randomized clinical trial that directly compared tirzepatide (Zepbound) to semaglutide (Wegovy) for weight loss in 751 adults with obesity over 72 weeks. It was the first large, rigorous head-to-head study between these two medications and was published in the New England Journal of Medicine in May 2025.
2. How much more weight did tirzepatide patients lose than semaglutide patients? At 72 weeks, tirzepatide patients lost an average of 20.2% of their body weight compared to 13.7% with semaglutide — a difference of 6.5 percentage points. In pounds, that's roughly 50 lbs vs. 33 lbs for a 250-pound person.
3. Is tirzepatide better than semaglutide for everyone? Tirzepatide produces more weight loss on average, but the best medication for any individual depends on their full medical history, insurance coverage, cardiovascular risk, and how they tolerate each drug. Both are highly effective FDA-approved options.
4. Which has fewer side effects — Zepbound or Wegovy? In the SURMOUNT-5 trial, fewer patients stopped tirzepatide due to gastrointestinal side effects (2.7%) compared to semaglutide (5.6%). Both medications cause nausea and stomach upset in some patients, especially early in treatment during dose escalation.
5. How do I get tirzepatide or semaglutide in Shreveport? Both medications require a prescription from a physician. At Shreveport Direct Care, we offer a physician-led weight loss program that includes a full medical evaluation, lab work, and ongoing monitoring. Schedule a free meet-and-greet to find out if you're a candidate.
References
Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393(1):26-36. doi:10.1056/NEJMoa2416394
Eli Lilly and Company. Lilly's Zepbound demonstrated significantly greater weight reduction compared to Novo Nordisk's Wegovy in SURMOUNT-5 head-to-head trial. Press release. May 2025.
American College of Cardiology. SURMOUNT-5: Greater loss of weight, waist circumference with tirzepatide than semaglutide. ACC.org. July 10, 2025. https://www.acc.org/Latest-in-Cardiology/Journal-Scans/2025/07/10/09/09/SURMOUNT-5
Shreveport Direct Care is a direct primary care practice serving adults and children in Shreveport, Bossier City, and surrounding communities in Northwest Louisiana. Dr. Pat "Ricky" Bass III is board-certified in Internal Medicine and Pediatrics.