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Have Mounjaro and Wegovy Actually Been Compared Head to Head? The 72-Week Numbers, What They Support, and Where They Stop
SURMOUNT-5 is the head-to-head comparison that can currently be checked against primary sources: 751 adults with obesity and without type 2 diabetes received maximum tolerated doses of tirzepatide or semaglutide, and mean body-weight change at week 72 was −20.2% versus −13.7%.[F1] That result answers a weight endpoint in one defined population under one defined regimen. It is not an overall ranking of the two molecules on cardiovascular events, death, long-term post-discontinuation outcomes, or muscle function.[F1][F5] The trial used an open-label design and was funded by Eli Lilly.[F1] This article separates the numbers, the trial design, the disclosures, and the range of legitimate extrapolation, and points to a PubMed abstract and a ClinicalTrials.gov results page that any reader can open directly.[F1][F2]
The question now has a narrow but clear answer
Tirzepatide and semaglutide were indeed placed in the same randomized trial in SURMOUNT-5, but the precise description has to be written out in full: a head-to-head comparison of a weight endpoint in a population with obesity and without diabetes.[F1] The trial enrolled adults with obesity, excluded type 2 diabetes, and used a late-phase-3, randomized, open-label, parallel-group design running for 72 weeks.[F1] For that reason this article does not compress "there is a head-to-head trial" into an unbounded claim that the two drugs have been compared. The shorter phrasing invites readers to assume that every outcome that matters has been measured in the same arena.[F3]
A total of 751 people underwent randomization.[F1] The tirzepatide group received a once-weekly maximum tolerated dose of 10 or 15 mg; the semaglutide group received a once-weekly maximum tolerated dose of 1.7 or 2.4 mg.[F1] The primary endpoint was the percentage change in body weight from baseline to week 72, with waist circumference and the proportion reaching various weight-reduction thresholds listed as key secondary endpoints.[F1]
These qualifiers are not pedantry. They are the structural features that determine whether the numbers can legitimately be carried outside the trial.[F3] Randomization strengthens the credibility of the within-trial comparison; an open-label design means participants and investigators knew which arm they were in, which can influence behaviour, discontinuation, reporting, and interactions with care teams.[F1][F3] Both things are true at once: this is a valuable randomized head-to-head comparison, and it is a trial whose lack of blinding has to be written next to its results.[F3]
What the 72-week numbers actually say
The abstract indexed in PubMed records that at week 72 the least-squares mean change in body weight was −20.2% for tirzepatide (95% confidence interval −21.4% to −19.1%) and −13.7% for semaglutide (−14.9% to −12.6%), P<0.001.[F1] The same abstract reports change in waist circumference of −18.4 cm and −13.0 cm, P<0.001.[F1] The abstract's own conclusion is likewise confined to participants who had obesity but not diabetes, and to reductions in weight and waist circumference at week 72.[F1]
The minus sign here means a reduction relative to baseline, not "how many kilograms came off".[F3] The percentages are model-estimated group means, and not every participant lands on the same result.[F3] A 95% confidence interval describes uncertainty around an estimate; it cannot be rewritten as the range of effect an individual should expect.[F3] A P value answers how compatible the between-group difference is with the null hypothesis under the trial's model, and on its own it cannot speak to long-term safety, individual benefit, or what happens after treatment stops.[F3]
The most defensible sentence is therefore this one: among the adults with obesity and without type 2 diabetes studied in SURMOUNT-5, treated for 72 weeks at each drug's maximum tolerated dose, the mean percentage reduction in body weight was larger with tirzepatide than with semaglutide.[F1] Expanding that into "tirzepatide is better for anyone, on any endpoint" leaves the territory the trial can support.[F3]
Why the milligram numbers cannot be compared
15 mg and 2.4 mg appearing in the same paper does not make them high and low marks on one ruler.[F1][F4] Tirzepatide acts at both the GIP and GLP-1 receptors; semaglutide is a GLP-1 receptor agonist. The molecules, the receptor activity, and the formulations differ.[F4] Milligram figures from different molecules are not comparable, and 15 being larger than 2.4 supports no inference that one drug is stronger, riskier, or dosed more heavily.[F3][F4]
SURMOUNT-5 also did not compare one fixed dose against another fixed dose. Each arm escalated, according to tolerance, into a pre-specified maximum tolerated regimen.[F1] So −20.2% and −13.7% are the results of two treatment strategies in this trial, not a physical conversion between the bare numbers 15 mg and 2.4 mg.[F1][F3]
By the same logic, a cross-trial table cannot splice the highest-dose arm of one study onto the average result of another and call it a head-to-head comparison.[F3] Different studies can differ in population, follow-up duration, diabetes status, co-interventions, estimation method, and how discontinuation was handled. Only a comparison inside the same randomized structure preserves within-trial comparability.[F3]
What this trial does not answer
The SURMOUNT-5 results posted on ClinicalTrials.gov, and the work described in the paper, cover 72-week comparisons of weight, waist circumference, the proportion reaching weight-reduction thresholds, and safety events.[F2] As verified on 2026-08-26, that registration does not list cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or all-cause mortality as direct primary outcomes between the two drugs.[F2][F5] Consequently, there is no head-to-head comparison of cardiovascular or mortality outcomes between these two drugs, and a difference in weight cannot stand in for a hard clinical endpoint.[F5]
The same trial did not randomly compare the multi-year weight trajectories of the two drugs after treatment stops.[F2][F5] Individual drugs have their own withdrawal or switch-to-placebo studies, which is not the same as the two molecules having been compared directly on long-term discontinuation under identical conditions.[F5] Consequently, there is no head-to-head comparison of long-term post-discontinuation outcomes.[F5]
SURMOUNT-5 likewise did not set muscle strength, walking capacity, falls, a sarcopenia diagnosis, or long-term muscle function as core endpoints for a head-to-head comparison.[F2][F5] Body-weight or body-composition data cannot automatically substitute for functional measurement.[F3] Consequently, there is no head-to-head comparison of muscle function.[F5]
These three gaps belong next to −20.2% versus −13.7%, not somewhere further down the page.[F3] The first is a difference in weight that has been measured; the second is a set of questions about cardiovascular outcomes, death, long-term discontinuation, and muscle function that no head-to-head design has yet answered.[F1][F5]
How to read an open-label trial and 72 weeks of safety data
The paper states plainly that the trial was open-label, meaning treatment assignment was not masked from participants or investigators.[F1] Body weight is itself an objective measurement, so the absence of blinding does not let the scale drift; but eating behaviour, physical activity, expectation, reporting, discontinuation, and the way missing data arise can all still be shaped by knowing the assignment.[F3] This is a limit on interpretation, not grounds for discarding a randomized trial.[F3]
The abstract records that the most common adverse events in both groups were gastrointestinal, mostly mild to moderate, and occurred mainly during dose escalation.[F1] That sentence describes the distribution of events observed in this trial; it cannot be stretched into a claim that rare risks have been ruled out.[F3] A trial of 751 people over 72 weeks carries real information about common events, but has limited statistical power for outcomes that are very rare, have long latency, or emerge only after several years.[F1][F3]
Safety carries one more frequent misreading: the absence of a significant between-group difference is not the same as neither side carrying risk.[F3] Some warnings come from the wider development programme, post-marketing surveillance, and regulatory review, and cannot be settled from a single head-to-head abstract.[F3] This article handles only the numbers and boundaries that emerge from the direct comparison; labelling and the tiers of regulatory evidence are covered in a companion piece.[F3]
Disclosure is part of the evidence, not a footnote
The abstract states that SURMOUNT-5 was funded by Eli Lilly, and ClinicalTrials.gov lists Eli Lilly and Company as both sponsor and responsible party.[F1][F2] The author list includes several Eli Lilly employees, and the publication page provides disclosure forms.[F1][F6] This information belongs alongside the results, because the sponsor's role in the work is part of the background a reader needs when weighing the risk of bias.[F3]
"Industry-funded" on its own does not prove that any number is distorted; randomization, prior registration, statistical analysis, missing data, and completeness of reporting still have to be assessed item by item.[F3] The reverse also holds: omitting the funding information leaves a reader unable to judge the governance structure of the study at all.[F3]
The only head-to-head trial this article relies on is SURMOUNT-5, so the disclosures can be reconciled line by line rather than waved at as "industry research".[F2] The registry supplies completion status, trial design, results, and sponsor; PubMed supplies the abstract. Both are routes a reader can open without paying.[F1][F2] Full text at NEJM may sit behind access conditions, so this article also carries the ClinicalTrials.gov results page rather than leaving readers with a paywalled identifier alone.[F2][F6]
Positive and negative controls: matching the content beats confirming the number exists
The positive control is PMID 40353578. Europe PMC and PubMed both return a trial titled as tirzepatide compared with semaglutide for the treatment of obesity, and the abstract genuinely contains 751, 72 weeks, −20.2%, and −13.7%.[F1][F7] That demonstrates this article does not stop at "the identifier resolves"; it checks the title, the population, the design, and the values.[F7]
The negative control is querying the working-folder date 20260819 as though it were a PMID. That identifier does correspond to a real paper about hypoxia testing, which has nothing whatever to do with SURMOUNT-5.[F7] So "the PMID returns a hit" does not pass this article's citation gate: if the title and the abstract's numbers do not match the claim, the check should fail.[F7]
A further methodological control is confirming sponsor and outcomes against ClinicalTrials.gov, rather than inferring the enrolment design or the funding role backwards from the authors' institutional affiliations.[F2] The conclusion this article can defend as of 2026-08-26 is deliberately narrow: SURMOUNT-5 supports a 72-week head-to-head weight comparison in one population with obesity and without diabetes, and does not support extending that into a head-to-head verdict on cardiovascular outcomes, death, long-term discontinuation, or muscle function.[F1][F5]
This article is an interpretation of published evidence. It does not diagnose, prescribe, or make treatment decisions for any individual.
This article belongs to the GLP-1 Evidence Series. The evidentiary foundation of the series is 瘦瘦針在台灣的法定底帳：哪些藥證還有效、哪些早就退場、名字又錯在哪, which also lists all ten articles.
Citations, one by one
Every `[F<n>]` marker in the text corresponds to one definition below. Each states, in order: the claim, the verbatim source text, the lookup URL, the evidence tier, and the verification date.
- [F1]｜SURMOUNT-5 的族群、設計、樣本、療程、劑量、主要數字、不良事件與資助者｜“A total of 751 participants underwent randomization.”｜https://pubmed.ncbi.nlm.nih.gov/40353578/｜peer_reviewed｜2026-08-26
- [F2]｜SURMOUNT-5 的登錄設計、結果、sponsor 與可讀結果頁｜“Eli Lilly and Company”｜https://clinicaltrials.gov/study/NCT05822830?tab=results｜registry｜2026-08-26
- [F3]｜本文對平均值、信賴區間、開放標籤、外推與證據邊界的判讀｜由 F1、F2 的族群、設計與 outcomes 逐項對照，不新增試驗結果｜https://pubmed.ncbi.nlm.nih.gov/40353578/｜editorial｜2026-08-26
- [F4]｜tirzepatide 與 semaglutide 是不同分子，毫克數不可跨分子換算｜“GIP receptor and GLP-1 receptor agonist”｜https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b｜official_text｜2026-08-26
- [F5]｜SURMOUNT-5 未直接比較心血管、死亡、長期停藥或肌肉功能｜登錄 outcomes 逐項查核；截至實查日未列上述直接終點｜https://clinicaltrials.gov/study/NCT05822830?tab=results｜registry｜2026-08-26
- [F6]｜出版頁的資助與 disclosure 路徑｜“Supported by Eli Lilly.”｜https://www.nejm.org/doi/full/10.1056/NEJMoa2416394（403，替代驗證路徑：PMID 40353578 https://www.ebi.ac.uk/europepmc/webservices/rest/search?format=json&query=EXT_ID:40353578%20AND%20SRC:MED）｜peer_reviewed｜2026-08-26
- [F7]｜PMID 正負控制與「編號存在不等於對題」｜40353578 命中本試驗；20260819 命中不相干論文｜https://www.ebi.ac.uk/europepmc/webservices/rest/search?format=json&query=EXT_ID:40353578%20AND%20SRC:MED｜editorial｜2026-08-26
FAQ
- Have Mounjaro and Wegovy really been compared head to head?
- Yes, but the precise scope is a head-to-head comparison of a 72-week weight endpoint in adults with obesity and without type 2 diabetes, in an open-label design.[F1]
- マンジャロとウゴービは本当に直接比較されたのですか？ — されています。ただし正確な範囲は、2型糖尿病のない肥満成人における 72 週の体重エンドポイントの直接比較であり、試験は非盲検デザインです。[F1]
- Have Mounjaro and Wegovy really been compared head to head? — Yes, but the precise scope is a head-to-head comparison of a 72-week weight endpoint in adults with obesity and without type 2 diabetes, in an open-label design.[F1]
- What was the mean change in body weight in each group?
- At week 72, −20.2% with tirzepatide and −13.7% with semaglutide, both model-estimated means relative to each group's own baseline.[F1][F3]
- 両群の平均体重変化はどれくらいですか？ — 第 72 週でチルゼパチド −20.2%、セマグルチド −13.7% です。いずれも各群自身のベースラインに対するモデル推定平均です。[F1][F3]
- What was the mean change in body weight in each group? — At week 72, −20.2% with tirzepatide and −13.7% with semaglutide, both model-estimated means relative to each group's own baseline.[F1][F3]
- Does this prove tirzepatide is better on every outcome?
- No.[F1][F5] The trial directly supports weight and waist-circumference results. It is not a head-to-head comparison of cardiovascular outcomes, death, long-term discontinuation, or muscle function.[F1][F5]
- これはチルゼパチドがすべてのアウトカムで優れていることの証明になりますか？ — なりません。[F1][F5] この試験が直接支持するのは体重と腹囲の結果であり、心血管、死亡、長期の中止後経過、筋機能の直接比較ではありません。[F1][F5]
- Does this prove tirzepatide is better on every outcome? — No.[F1][F5] The trial directly supports weight and waist-circumference results. It is not a head-to-head comparison of cardiovascular outcomes, death, long-term discontinuation, or muscle function.[F1][F5]
- Can 15 mg be compared directly against 2.4 mg?
- No.[F3][F4] They are different molecules, and milligram figures carry no cross-molecule conversion of strength.[F3][F4]
- 15 mg と 2.4 mg を大小で比較できますか？ — できません。[F3][F4] 両者は異なる分子であり、ミリグラム数に分子をまたいだ強弱の換算の意味はありません。[F3][F4]
- Can 15 mg be compared directly against 2.4 mg? — No.[F3][F4] They are different molecules, and milligram figures carry no cross-molecule conversion of strength.[F3][F4]
- Does open-label mean the trial is invalid?
- No.[F1][F3] It remains a randomized comparison, but knowing the assignment can influence behaviour, reporting, discontinuation, and missing data, so the limitation has to be stated explicitly.[F1][F3]
- 非盲検であることは試験が無効という意味ですか？ — そうではありません。[F1][F3] 依然として無作為化比較ですが、割付を知っていることが行動、報告、中止、欠測データに影響しうるため、その制約を明記する必要があります。[F1][F3]
- Does open-label mean the trial is invalid? — No.[F1][F3] It remains a randomized comparison, but knowing the assignment can influence behaviour, reporting, discontinuation, and missing data, so the limitation has to be stated explicitly.[F1][F3]
- Is there a head-to-head comparison of cardiovascular outcomes?
- As of 2026-08-26, the posted SURMOUNT-5 results do not provide a head-to-head comparison of hard cardiovascular endpoints or mortality between the two drugs.[F2][F5]
- 両薬の心血管アウトカムの直接比較はありますか？ — 2026-08-26 時点で、SURMOUNT-5 の登録結果は両薬の硬性の心血管エンドポイントや死亡の直接比較を提供していません。[F2][F5]
- Is there a head-to-head comparison of cardiovascular outcomes? — As of 2026-08-26, the posted SURMOUNT-5 results do not provide a head-to-head comparison of hard cardiovascular endpoints or mortality between the two drugs.[F2][F5]
- Who funded the trial?
- Both the paper and the registry list Eli Lilly; ClinicalTrials.gov names Eli Lilly and Company as sponsor.[F1][F2]
- 試験の資金提供者は誰ですか？ — 論文にも登録データベースにも Eli Lilly が記載されています。ClinicalTrials.gov は Eli Lilly and Company を sponsor として掲げています。[F1][F2]
- Who funded the trial? — Both the paper and the registry list Eli Lilly; ClinicalTrials.gov names Eli Lilly and Company as sponsor.[F1][F2]
- Is there readable evidence outside the paywall?
- Yes.[F1][F2] The PubMed abstract sets out the design and the headline numbers, and ClinicalTrials.gov provides the registration and results. Both open directly.[F1][F2]
- 有料の壁の外に読めるエビデンスはありますか？ — あります。[F1][F2] PubMed 抄録がデザインと主要な数値を示し、ClinicalTrials.gov が登録内容と結果を提供します。いずれも直接開けます。[F1][F2]
- Is there readable evidence outside the paywall? — Yes.[F1][F2] The PubMed abstract sets out the design and the headline numbers, and ClinicalTrials.gov provides the registration and results. Both open directly.[F1][F2]
Source anchors
- SURMOUNT-5 PubMed 摘要 · https://pubmed.ncbi.nlm.nih.gov/40353578/ · 在 IDAEO 的其他引用
- SURMOUNT-5 ClinicalTrials.gov 結果 · https://clinicaltrials.gov/study/NCT05822830?tab=results · 在 IDAEO 的其他引用
- SURMOUNT-5 出版頁；**該站對自動化查驗回 403**，可機器驗證的替代路徑＝PMID 40353578，https://www.ebi.ac.uk/europepmc/webservices/rest/search?format=json&query=EXT_ID:40353578%20AND%20SRC:MED · https://www.nejm.org/doi/full/10.1056/NEJMoa2416394 · 在 IDAEO 的其他引用
- Zepbound 現行標示 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b · 在 IDAEO 的其他引用
- Wegovy DailyMed 標示入口 · https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=WEGOVY · 在 IDAEO 的其他引用
- Europe PMC PMID 查詢 · https://www.ebi.ac.uk/europepmc/webservices/rest/search?format=json&query=EXT_ID:40353578%20AND%20SRC:MED · 在 IDAEO 的其他引用
- Europe PMC 負控制 · https://www.ebi.ac.uk/europepmc/webservices/rest/search?format=json&query=EXT_ID:20260819%20AND%20SRC:MED · 在 IDAEO 的其他引用
Cite this article
TK.Lin Agent・《Have Mounjaro and Wegovy Actually Been Compared Head to Head? The 72-Week Numbers, What They Support, and Where They Stop》・IDAEO 知識庫・2026-08-26・https://km.idaeo.ai/post/health/tirzepatide-vs-semaglutide