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Posted on 05/12/2025 5:20:30 PM PDT by Red Badger
In a nutshell
* Tirzepatide (Mounjaro) produced 20.2% weight loss compared to semaglutide’s (Wegovy) 13.7% after 72 weeks of treatment Tirzepatide users experienced greater waistline reduction (7.2 inches vs. 5.1 inches) and more significant improvements in health markers
* Both medications caused similar side effects, but fewer people discontinued tirzepatide due to stomach issues (2.7% vs. 5.6%)
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NEW YORK — For the first time, scientists have pitted the two most popular weight loss drugs against each other in a direct competition – and one clearly dominates. A new study led by Weill Cornell Medicine researchers reveals that tirzepatide (Mounjaro, Zepbound) helps people lose significantly more weight than semaglutide (Wegovy).
The difference is striking: people taking tirzepatide lost 20.2% of their body weight over 72 weeks, while those on semaglutide dropped 13.7%. For a 250-pound person, that translates to about 50 pounds with tirzepatide versus 34 pounds with semaglutide – a 16-pound gap that could dramatically impact quality of life.
Results of the study are published in the New England Journal of Medicine.
Tirzapetide vs. Semaglutide
Both medications work by mimicking hormones that our bodies naturally produce, but they target different receptors. Semaglutide activates only one hormone pathway – glucagon-like peptide-1 (GLP-1) – which helps control appetite and slows digestion. Tirzepatide hits that same GLP-1 target but also activates a second hormone called GIP. This dual-action approach appears to be more effective for weight loss.
The SURMOUNT-5 trial, led by Dr. Louis Aronne from Weill Cornell Medicine, recruited 751 adults with obesity but without diabetes. Half received weekly tirzepatide injections, while the other half got weekly semaglutide shots. Both medications required gradual dose increases to reach their maximum strength.
Zepbound is another tirzepatide brand.
Beyond the Scale: Health Benefits and Waistline Reduction
The benefits extended beyond just weight. Tirzepatide users saw their waistlines shrink by 7.2 inches on average, compared to 5.1 inches with semaglutide. This difference matters because abdominal fat surrounds vital organs and increases the risk of heart disease, diabetes, and other conditions.
As weight dropped, health markers improved with both medications. Blood pressure, blood sugar, and cholesterol levels all showed improvements, with tirzepatide generally showing a stronger effect. Participants who lost more weight – especially those dropping 20% or more – experienced the most significant health improvements.
Side Effects and Real-World Implications
Stomach issues topped the side effect list for both medications – nausea affected about 44% of participants in both groups, while constipation troubled roughly 28%. Interestingly, twice as many people quit taking semaglutide due to digestive problems (5.6% versus 2.7% for tirzepatide).
Demand for weight loss medications continues to climb, with both manufacturers struggling to meet demand amid ongoing shortages. Insurance coverage remains inconsistent, forcing many patients to pay over $1,000 monthly out-of-pocket for either medication.
With the CDC estimating that more than 35% of American adults living with obesity – which increases risks for heart disease, stroke, diabetes, and certain cancers – these medications represent a major advance in treatment options. However, they work best alongside lifestyle changes like healthier eating and regular physical activity.
As remarkable as these results are, they come with limitations. The trial was open-label, meaning participants knew which medication they were receiving. And though the medications were tested for 72 weeks, obesity is a chronic condition requiring long-term management. Questions remain about what happens when people stop taking these medications, with some studies suggesting significant weight regain.
For now, tirzepatide has claimed the weight loss crown. The outstanding question is whether its superior results will justify what will likely be a higher price tag – and whether insurance companies will agree to cover it.
Paper Summary
Methodology
The SURMOUNT-5 trial was a phase 3b, multicenter, open-label, randomized controlled trial conducted at 32 sites in the United States and Puerto Rico. A total of 751 adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one obesity-related complication were randomly assigned in a 1:1 ratio to receive either tirzepatide or semaglutide. Participants received weekly subcutaneous injections for 72 weeks, with tirzepatide doses starting at 2.5mg and increasing to a maximum tolerated dose of 10mg or 15mg, and semaglutide starting at 0.25mg and increasing to a maximum tolerated dose of 1.7mg or 2.4mg. The primary endpoint was percent change in weight from baseline to week 72, with key secondary endpoints including weight reductions of at least 10%, 15%, 20%, and 25%, and change in waist circumference.
Results
Tirzepatide demonstrated superior efficacy compared to semaglutide across all primary and secondary endpoints. The least-squares mean percent change in weight at week 72 was -20.2% with tirzepatide versus -13.7% with semaglutide (p<0.001). The least-squares mean change in waist circumference was -18.4cm with tirzepatide and -13.0cm with semaglutide (p<0.001). More participants in the tirzepatide group achieved weight reductions of at least 10% (81.6% vs 60.5%), 15% (64.6% vs 40.1%), 20% (48.4% vs 27.3%), and 25% (31.6% vs 16.1%). For the exploratory endpoint of weight reduction of at least 30%, tirzepatide was superior at 19.7% versus 6.9% for semaglutide. Both medications also improved cardiometabolic risk factors including blood pressure, glycated hemoglobin, fasting serum glucose, and lipid levels, with more significant improvements observed with tirzepatide.
Limitations
The trial had several limitations. It was open-label, meaning participants and investigators knew which medication they were receiving, which could have influenced results. Though the trial lasted 72 weeks, obesity is a chronic condition requiring long-term management, so longer-term efficacy and safety data would be valuable. The study also included a higher percentage of men (35%) than previous similar trials, which may have affected the overall weight reduction results since men in both groups lost approximately 6% less weight than women.
Funding and Disclosures
The study was funded by Eli Lilly, the manufacturer of tirzepatide. Multiple authors reported financial relationships with Eli Lilly, including employment. The sponsor was involved in the trial design, data collection, site monitoring, data analysis, and manuscript preparation.
Publication Information
The paper titled “Tirzepatide as Compared with Semaglutide for the Treatment of Obesity” was published in the New England Journal of Medicine on May 11, 2025. The trial was registered on ClinicalTrials.gov (number NCT05822830) under the name SURMOUNT-5. The lead author was Louis J. Aronne from the Comprehensive Weight Control Center, Division of Endocrinology, Diabetes, and Metabolism at Weill Cornell Medicine.
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I’d like to see some data on meth against these two. Sure it has some bad side effects but so do these.
Key info:
*** The study was funded by Eli Lilly, the manufacturer of tirzepatide. Multiple authors reported financial relationships with Eli Lilly, including employment. The sponsor was involved in the trial design, data collection, site monitoring, data analysis, and manuscript preparation.***
I would expect that people can still get Ozempic face from the other drug, too, because I believe that is a result of rapid weight loss.
Well, with meth you lose weight and your teeth...............
I have friend who has been on both. Yes, she’s lost weight. 70 lbs, over a roughly, but not quite, a 1 year period. However, both medications made her nauseous, so yeah, she’s stopped eating. You’ll lose weight if you pretty much have no appetite because everything you eat makes you sick to your stomach. That’s what she’s dealing with.
There was a period when we were all congratulating her. That was about 35 pounds ago. Now she looks withdrawn in her face. She LOOKS sick now. It’s getting hard to watch. I hope she stops. She needs to put a few pounds back on. She is a very sweet and kind person. I don’t care what she looks like. I want her to feel good about herself, but at what cost?
Yes, my friend is on Mounjaro, and she has the same face. It’s awful.
I'm a 5'-10" 73 year old male. My IBW based on four models is shown below. I'm currently over 190, so 30 pounds to shed to reach the highest IBW. But, I do know if I actually hit 165, I'd be skin and bones and look terrible, same as you describe your friend.
How come we’ve stopped hearing about all the dangerous adverse effects? It seemed like for a while, you couldn’t go a week without hearing about someone who died or had irreversible intestinal problems, or had to be hospitalized.
Someone should do a documentary about how they choose the names for these modern drugs. I guess it’s probably heavily focused grouped, but I can’t help thinking someone in a far off third world village is saying “hey they named a drug after us.”
Freegards
Well, the first volunteer patient died. So they named it after him, Mounjaro.
It Kill a Mounjaro. ............
My wife hated Ozempic (semaglutide) but was ok with tirzepetide (Mounjaro, Trulicity). So that’s an official clinical trial right there.
When she told us she’d lost 70 lbs, well, I was surprised, because she never looked like she was that overweight for her height. I’m guessing she’s 5’5” or 5’6”. She’s lost it all over but it shows most in her face. She looks very withdrawn. I’m not sure what it is, but she looks much older, not younger.
I hope your wife isn’t my friend. If she is, please tell her she’s taken off enough weight. It looks like it’s hurting her at this point.
Has anybody here had a similar experience?
That’s what false teeth are for. Plus you get to pick them out! You can get the white white (which looks unnatural) OR you can opt for the extended eye teeth for the vampire look (my personal preference). But yeah, they all have some drawbacks.
My wife went from 250 to 140 with Mounjaro. She had no side effects.
That’s great! No side effects to boot!
Unfortunately many people do. I wonder if it has anything to do with genetics?
Or possibly something in their environment, like a certain food they continue to eat that reacts negatively with the meds?............
I’ve been on Mounjaro for 2 months and lost 16 pounds. You can see it in my face and all over. You have to work out while on Mounjaro to keep looking good. I’m not sure I can stay on it as the side effects are not great, so I’m taking a break for a short time and see how things go. I definitely want to lose another 34 pounds.
Unfortunately, I’m not on it just to lose weight. I was on Metformin which I couldn’t take, so Mounjaro is my second option and if it doesn’t work out, I’m not sure what’s next. More diet and exercise for sure.
I dont know where they are getting those ridiculous numbers.
Mine claims that I should be lighter than when I wrestled in high school and about 30lbs lighter than what the military expected. Of the weights they give as correct one is not only 30lbs lighter than what I wrestled, no I wasnt the chubby kid that just showed up, but there was no one on the team, not even that skinny spaghetti kid, that was making those weights without going to extreme ends at that height.
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