Tirzepatide: evidence brief
What was actually studied
SURPASS-2 measured glycemic change in type 2 diabetes; SURMOUNT-1 measured weight change without diabetes. SURMOUNT-4 tested continuation versus withdrawal after a tolerated lead-in. Different populations, comparators and time origins prevent a ranking across these trials.
- Version
- 2026-10-05.1
- Snapshot updated
Prepared by Peptides Codex. Independent review by a qualified subject specialist is pending.
Scope of this brief
Three selected primary trial reports of study-supplied subcutaneous tirzepatide (LY3298176), sponsored by Eli Lilly. Arm doses describe historical study conditions, not instructions. These findings do not authenticate research powders or other formulations. This is not an exhaustive review; qualified scientific review remains pending.
Frías et al., 2021 · SURPASS-2 · PMID 34170647
- Material tested
- Study-supplied subcutaneous tirzepatide (LY3298176), target arms 5/10/15 mg; subcutaneous semaglutide 1 mg comparator.
- Model or population
- Adults with type 2 diabetes inadequately controlled on metformin.
- Study design
- Phase 3, 40 weeks; randomized 1:1:1:1, open-label between products; tirzepatide dose groups double-blinded.
- Sample and comparison
- 1,879 randomized: 471/469/470 versus 469. Modified intention-to-treat analysis: 1,878 who received study drug (470/469/470 versus 469); missing values estimated.
- Reported finding
- Primary HbA1c change at week 40, treatment-regimen estimate: −2.01/−2.24/−2.30 percentage points for 5/10/15 mg versus −1.86 with semaglutide 1 mg. Each comparison favored tirzepatide (p=0.02/<0.001/<0.001).
- Limits of this evidence
- Open-label, 40-week glycemic comparison in diabetes; no comparison with semaglutide 2.4 mg for obesity. Gastrointestinal adverse events were common; this 40-week trial does not establish long-term safety.
Source access: Primary journal abstract, Methods and Results retrieved in indexed search; direct full-text access blocked. Registry participant flow cross-checked.
Primary source ↗: Frías et al., 2021 · SURPASS-2 · PMID 34170647
Jastreboff et al., 2022 · SURMOUNT-1 · PMID 35658024
- Material tested
- Study-supplied subcutaneous tirzepatide (LY3298176), target arms 5/10/15 mg versus matching placebo; lifestyle support in all groups.
- Model or population
- Adults without diabetes: BMI ≥30, or ≥27 with a weight-related complication.
- Study design
- Phase 3, randomized 1:1:1:1, double-blind, placebo-controlled; initial 72-week report.
- Sample and comparison
- 2,539 randomized and included in intention-to-treat analysis: 630/636/630 versus 643 placebo. Estimates include missing-data handling, not only participants completing treatment.
- Reported finding
- Coprimary outcomes at week 72, treatment-regimen estimates: mean weight change −15.0/−19.5/−20.9% for 5/10/15 mg versus −3.1% placebo; ≥5% weight loss in 85/89/91% versus 35%. All comparisons p<0.001.
- Limits of this evidence
- Initial 72-week placebo comparison without diabetes, excluding later follow-up; no active-drug ranking. Mean benefit must be considered alongside gastrointestinal adverse events and treatment discontinuations.
Source access: Primary abstract and indexed journal Methods/Results inspected; direct journal full-text access blocked. Official registry design and counts corroborated.
Primary source ↗: Jastreboff et al., 2022 · SURMOUNT-1 · PMID 35658024
Aronne et al., 2024 · SURMOUNT-4 · PMID 38078870
- Material tested
- Study-supplied subcutaneous tirzepatide (LY3298176), tolerated target 10 or 15 mg; continuation versus matching placebo after lead-in, with lifestyle support.
- Model or population
- Adults without diabetes: BMI ≥30, or ≥27 with a weight-related complication; randomization restricted to lead-in completers tolerating treatment.
- Study design
- Phase 3 withdrawal trial: 36-week open-label lead-in, then 52 weeks randomized 1:1, double-blind continuation versus placebo.
- Sample and comparison
- 783 entered lead-in; 782 received drug. 670 eligible tolerators randomized/analyzed, 335/group; 600 completed. The primary estimate includes all randomized participants with missing-data handling.
- Reported finding
- Primary estimated weight change from week 36 to 88: −5.5% continuing tirzepatide versus +14.0% after switching to placebo; difference −19.4 percentage points (95% CI −21.2 to −17.7; p<0.001).
- Limits of this evidence
- Withdrawal comparison in selected tolerators, not initial efficacy or tolerability among all 783 entrants. Lifetime benefit and safety are not established.
Source access: Primary JAMA full text inspected, including Methods, Results and limitations; official registry participant flow cross-checked.
Primary source ↗: Aronne et al., 2024 · SURMOUNT-4 · PMID 38078870
A finding applies to the material, model and conditions studied. It does not establish safety or effectiveness in other settings.
Help review this exact version
Qualified scientific review is pending. Source-backed corrections are welcome; a correction submission does not itself constitute expert approval.
Review reference: tirzepatide · 2026-10-05.1
What a reviewer should check
- Does the reported material match the preparation actually studied?
- Do population, participant counts and analysis denominators match the source?
- Are estimates, endpoints, uncertainty and missing-data methods represented accurately?
- Do limitations, source-access boundaries and English/French text preserve the same conclusion?
Study records in this version
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