Forums›Tirzepatide (Mounjaro / Zepbound)›SURMOUNT-5: Tirzepatide vs semaglutide head-to-head — looking for input

SURMOUNT-5: Tirzepatide vs semaglutide head-to-head — looking for input

MounjBrad Thu, Jul 3, 2025 at 1:46 AM 25 replies 1,608 viewsPage 1 of 5

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MounjBrad

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Jul 3, 2025 at 1:46 AM#1

I spent 3 months researching before choosing between tirzepatide and semaglutide. I'm a data analyst by profession so I built a literal decision matrix. Thought I'd share for anyone currently deciding. My profile: 39F, BMI 36.2, prediabetic (A1c 5.9), no prior GLP-1 experience, good insurance that covers both. Decision factors I evaluated: 1. Efficacy — Tirz wins. SURMOUNT-1 showed 20.9% weight loss at max dose vs. STEP-1's 14.9% for sema. 2. Mechanism — Tirz is dual GIP/GLP-1, sema is GLP-1 only. More pathways = potentially more durable effect. 3. Side effect profile — Mixed. GI sides similar in incidence, some evidence tirz has more sulfur burps but less nausea at equivalent efficacy doses. 4. Dosing flexibility — Tirz has 6 dose levels (2.5/5/7.5/10/12.5/15), sema has 4 (0.25/0.5/1/1.7 for Ozempic or 0.25/0.5/1/1.7/2.4 for Wegovy). More granularity with tirz. 5. Track record — Sema has been around longer (approved 2017 for T2D). Tirz approved 2022. Longer safety track record for sema. 6. Cost — Similar out of pocket with my insurance. Cash price: Mounjaro ~$1,050/mo, Wegovy ~$1,350/mo. 7. Supply — Sema has had WORSE shortage issues historically. My verdict: Tirzepatide, primarily on efficacy and dosing flexibility. But it was closer than the internet makes it seem. They're both excellent medications. What factors influenced YOUR decision? 🤔

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KevinCompounds

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Jul 3, 2025 at 2:55 AM#2

Great framework. I'll add some nuance to your efficacy comparison because it matters: The SURMOUNT vs. STEP comparison isn't perfectly apples-to-apples because the trial populations differed (SURMOUNT had higher baseline BMI on average). The most direct comparison we have is SURPASS-2, which compared tirzepatide to semaglutide 1mg head-to-head: > SURPASS-2 results: Tirzepatide 15mg achieved -12.4 kg greater weight reduction compared to semaglutide 1mg at 40 weeks. All tirzepatide doses (5, 10, 15mg) were superior to semaglutide 1mg. However, this compared tirz to sema 1mg, not 2.4mg. We don't have a head-to-head trial of tirz 15mg vs. sema 2.4mg, which would be the true max-dose comparison. The gap might be narrower than cross-trial comparisons suggest. That said, every available data point favors tirzepatide for weight loss efficacy. The question is whether that margin matters enough for any given individual.

Last edited: Jul 3, 2025 at 4:55 AM

49 2Dr.RaviCardio, jennifer_SEA, tyler_CSCS and 46 others

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hans_munich

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Jul 3, 2025 at 4:05 AM#3

I actually chose semaglutide and I'm happy with my decision. Here's my counter-framework: 1. Track record — You mentioned this briefly but I weighted it heavily. Semaglutide has 8+ years of post-marketing safety data. The SELECT cardiovascular outcomes trial showed a 20% reduction in MACE. Tirzepatide's CV outcomes trial (SURPASS-CVOT) is still ongoing. 2. Oral option — Semaglutide is available as oral Rybelsus. I hate needles. Started on oral sema and only switched to injectable when I needed a higher dose. Tirz has no oral option yet. 3. More prescriber experience — My endo has managed hundreds of patients on sema vs. maybe 50-60 on tirz. That clinical experience with dosing, side effect management, and troubleshooting matters. 4. "Good enough" efficacy — I've lost 48 lbs on Wegovy 2.4mg (16 months). That's life-changing. Did I leave 10-15 lbs on the table vs. tirz? Maybe. But 48 lbs solved my sleep apnea, normalized my blood pressure, and made me feel like a new person. Not everything needs to be optimized to the maximum. Sometimes "really good" is enough. 💪

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PeptideChemSF

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Jul 3, 2025 at 5:15 AM#4

really good point about the lack of a true head-to-head max dose comparison. That's a gap in the evidence I should have noted. I respect this so much. The "good enough" framing is something we data people tend to overlook — we chase the optimal solution when the satisfactory solution is already transformative. And the CV outcomes data for sema is genuinely compelling. That SELECT trial was a landmark.

Last edited: Jul 3, 2025 at 9:15 AM

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raj_cambridge

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Jul 3, 2025 at 11:56 AM#5

Obesity medicine physician here. My approach to recommending one vs. the other: I lean toward tirzepatide when: - Patient has >50 lbs to lose (greater efficacy may matter more) - Patient has insulin resistance or T2D (dual mechanism targets this powerfully) - Patient has tried semaglutide and plateaued - Patient prefers fewer dose adjustments (tire achieves therapeutic effect at lower relative doses) I lean toward semaglutide when: - Patient prefers oral medication option - Patient has established cardiovascular disease (SELECT trial data) - Patient is concerned about long-term safety data (longer track record) - Cost/insurance favors it - Patient is in an area with tirz supply issues I tell all patients: Both medications represent a revolution in obesity treatment. The difference between them is far smaller than the difference between either of them and no treatment. You can't make a wrong choice here.

Last edited: Jul 3, 2025 at 12:56 PM

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