Tirzepatide vs. semaglutide head-to-head: what the trial actually shows
Quick answer
SURMOUNT-5 (Jastreboff et al., 2025, NEJM) is the first randomized, double-blind, head-to-head trial comparing tirzepatide (10-15 mg weekly) to semaglutide 2.4 mg weekly in 751 adults with obesity and without type 2 diabetes over 72 weeks. Tirzepatide produced approximately 20% mean body weight loss versus approximately 14% for semaglutide, a statistically significant difference driven by tirzepatide's dual GIP and GLP-1 receptor agonism. Clinical decisions should account for formulary access, tolerability, and individual patient factors beyond trial-level averages.
Our take · Written by FormBlends editorial team · Reviewed by FormBlends Medical Team· This is not a transcript. It is our independent review of the video above.
What did @drdavidalfery actually say?
The creator walked through the SURMOUNT-5 trial, published in the New England Journal of Medicine, which he called "the first and only head-to-head trial" of tirzepatide versus semaglutide for obesity. He reported that tirzepatide users lost an average of 50 pounds (about 20% body weight) compared to 33 pounds (about 14%) for semaglutide, over 72 weeks. He also noted waistline reductions of 7 inches versus 5 inches, and roughly similar dropout rates due to side effects (6% vs. 8%). He then pivoted to cost and compounding, noting Eli Lilly and Novo Nordisk direct-to-consumer programs, lawsuits against compounders, and CVS Caremark's decision to prefer semaglutide on formulary.
That is a lot of ground for one TikTok. Most of it holds up. Some of it needs context.
Does the science back this up?
On the trial results, yes, largely. The numbers he cited are consistent with what was published. The SURMOUNT-5 trial (Jastreboff et al., 2025, NEJM) randomized 751 adults with obesity and without diabetes to tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks.
- Tirzepatide group: mean body weight reduction of approximately 20.2% (roughly 22.8 kg, or about 50 lbs for an average participant weight)
- Semaglutide group: mean body weight reduction of approximately 13.7% (roughly 15.5 kg, or about 34 lbs)
- Waist circumference reductions: approximately 18.4 cm tirzepatide vs. 13.0 cm semaglutide, which translates loosely to about 7 vs. 5 inches
- Discontinuation due to adverse events: 6% tirzepatide, 8% semaglutide
His numbers are in the right ballpark. The percentage figures (20% vs. 14%) are accurate representations of the primary endpoint. The trial was prospective, randomized, double-blind, and active-controlled, which he correctly described.
What did they get wrong (or right)?
He got the trial data right. Where things get messier is his framing of industry funding and his comments on compounding.
His defense of Eli Lilly funding the study is nuanced but fair. He correctly points out that industry-funded trials of this scale are essentially the only trials that exist, and that peer review serves as a structural check. That is an honest take, not spin. Researchers like Lundh et al. (2017, Cochrane) have documented that industry-funded trials do tend to produce more favorable results, but that does not automatically invalidate SURMOUNT-5's methodology.
His statement that compounders "are going to lose" is an opinion stated as near-certainty. The FDA's shortage designations and legal landscape are still evolving. He is probably right directionally, but presenting this as settled is an overreach.
One thing he glossed over: the semaglutide dose used in SURMOUNT-5 was 2.4 mg weekly (Wegovy), not the 1 mg dose used in Ozempic for diabetes. Viewers conflating the two could draw the wrong conclusions about their own medication.
What should you actually know?
SURMOUNT-5 is a real, well-designed trial and its results are meaningful. Tirzepatide, a dual GIP/GLP-1 agonist, consistently outperforms semaglutide, a GLP-1-only agonist, across multiple outcomes in people with obesity. That is not just one Lilly-funded study. Trials like SURMOUNT-1 (Jastreboff et al., 2022, NEJM) and STEP 1 (Wilding et al., 2021, NEJM) established the benchmarks for each drug individually, and SURMOUNT-5 is the first direct comparison.
But "better" in a clinical trial is not the same as "better for you." Insurance coverage, side effect profile, individual response, and cost all shape real-world outcomes. The CVS Caremark formulary decision the creator mentioned actually means millions of people with that pharmacy benefit will have easier access to semaglutide than tirzepatide, regardless of what SURMOUNT-5 showed. A drug you can afford and tolerate beats a drug you cannot access.
On compounding: the creator correctly described the legal pressure on compounders but stopped short of saying compounded GLP-1 products are not equivalent to brand-name drugs. They are not. Compounded tirzepatide and semaglutide are not FDA-approved, have not been tested for bioequivalence, and carry different risk profiles. Patients using compounded versions should discuss this directly with their prescriber.
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Compounded Semaglutide access requires the right clinical path
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This page currently connects to 10 source-backed evidence items through visible references or structured citation data.
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Research sources used to frame this page
For Tirzepatide vs. semaglutide head-to-head: what the trial actually shows, FormBlends checks the page topic against primary trials, systematic reviews, guidelines, and current PubMed-indexed literature where available. These citations are context, not medical advice, proof of eligibility, or a claim that every study applies to every patient.
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Primary STEP 1 trial source for semaglutide weight-management efficacy and adverse-event context.
PubMed
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance
Used for maintenance, discontinuation, and weight-regain discussions after semaglutide response.
PubMed
Tirzepatide Once Weekly for the Treatment of Obesity
Primary SURMOUNT-1 trial source for tirzepatide weight-loss ranges and tolerability.
PubMed
Continued Treatment With Tirzepatide for Maintenance of Weight Reduction
Used for continuation, stopping, and maintenance questions after initial weight loss.
PubMed
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Direct answer
Compounded Semaglutide is best used to compare access, oversight, pricing, pharmacy quality, and patient support before starting care.
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Claim path
Keep researching this semaglutide video claims cluster
Best for searchers comparing social semaglutide claims with GLP-1 eligibility, outcomes, and safety context.
Claim verdict
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Claim being checked
SURMOUNT-5 (Jastreboff et al.
FormBlends verdict
SURMOUNT-5 (Jastreboff et al., 2025, NEJM) is the first randomized, double-blind, head-to-head trial comparing tirzepatide (10-15 mg weekly) to semaglutide 2.4 mg weekly in 751 adults with obesity and without type 2 diabetes over 72 weeks. Tirzepatide produced approximately 20% mean body weight loss versus approximately 14% for semaglutide, a statistically significant difference driven by tirzepatide's dual GIP and GLP-1 receptor agonism. Clinical decisions should account for formulary access, tolerability, and individual patient factors beyond trial-level averages.
Patient-safe next step
Compare the claim with the Compounded Semaglutide guide, safety notes, access rules, and a licensed-provider review.
What to do with this video
Use the clip as a claim to verify, not a treatment plan
What it helps with
- SURMOUNT-5 (Jastreboff et al., 2025, NEJM) is the first randomized, double-blind, head-to-head trial comparing tirzepatide (10-15 mg weekly) to semaglutide 2.4 mg weekly in 751 adults with obesity and without type 2 diabetes over 72 weeks. Tirzepatide produced approximately 20% mean body weight loss versus approximately 14% for semaglutide, a statistically significant difference driven by tirzepatide's dual GIP and GLP-1 receptor agonism. Clinical decisions should account for formulary access, tolerability, and individual patient factors beyond trial-level averages.
- SURMOUNT-5 (Jastreboff et al., 2025, NEJM) is the first randomized head-to-head trial of tirzepatide vs. semaglutide 2.4 mg for obesity, with 751 participants over 72 weeks.
- Tirzepatide produced roughly 20% mean body weight loss versus roughly 14% for semaglutide, a statistically significant difference across the 72-week period.
What it may miss
- It may not cover eligibility, contraindications, medication interactions, lab history, or dose escalation.
- Compounded Semaglutide decisions still need source quality, legal access, and provider oversight checks.
- Social video captions rarely show the full evidence base behind a claim.
Best next step
Compare the claim against the Compounded Semaglutide guide, cost path, safety notes, and provider review before acting.
Review Compounded SemaglutideWhat You'll Learn
- SURMOUNT-5 (Jastreboff et al., 2025, NEJM) is the first randomized head-to-head trial of tirzepatide vs. semaglutide 2.4 mg for obesity, with 751 participants over 72 weeks.
- Tirzepatide produced roughly 20% mean body weight loss versus roughly 14% for semaglutide, a statistically significant difference across the 72-week period.
- The semaglutide dose used was 2.4 mg weekly (Wegovy), not the lower 1 mg dose used in Ozempic for diabetes management. These are not interchangeable.
- Despite tirzepatide's superior trial results, formulary decisions like CVS Caremark preferring semaglutide mean real-world access often favors the less effective drug for many insured patients.
- Compounded tirzepatide and semaglutide are not FDA-approved and have not been tested for bioequivalence with brand-name versions. They carry different and less well-characterized risk profiles.
- Industry funding does not automatically invalidate a trial, but a 2017 Cochrane review (Lundh et al.) found industry-funded drug studies are more likely to report favorable results. Independent replication matters.
- Both drugs carry primarily gastrointestinal side effects. Discontinuation rates in SURMOUNT-5 were low (6-8%), but individual tolerability varies and should guide prescribing decisions alongside efficacy data.
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About the Creator
Dr. David Alfery · TikTok creator
65.7K views on this video
The first head-to-head trial of Semaglutide versus tirzepatide for losing weight has just been published. Which drug is better? ##semaglutide##tirzepatide##zepbound##wegovy##glp1##glp1 ##medicine##doctorsoftiktok##healthcare##obesity##weightliss
Sources & references
Citations extracted from our medical team's review. Click any citation to search PubMed.
Read More on This Topic
Our written guides go deeper with dosing details, comparison tables, and medical-team reviewed protocols.
Not medical advice. This video was made by Dr. David Alfery, not by FormBlends. Our write-up above is an editorial review, not a medical recommendation. Talk to your doctor before making any decisions about medications or treatments.