Tirzepatide is the only dual GIP/GLP-1 receptor agonist with a complete phase-3 obesity portfolio. The SURMOUNT program (Studies of tiRzepatide in oveRweight or obesity) ran six coordinated phase 3 trials between 2022 and 2025: obesity without diabetes (SURMOUNT-1), obesity with type 2 diabetes (SURMOUNT-2), intensive-lifestyle adjunct (SURMOUNT-3), maintenance vs withdrawal (SURMOUNT-4), head-to-head against semaglutide (SURMOUNT-5), Chinese adults (SURMOUNT-CN), and obstructive sleep apnea (SURMOUNT-OSA). Outside SURMOUNT, SYNERGY-NASH established efficacy in MASH/MASLD with liver fibrosis, the SUMMIT trial showed tirzepatide reduces heart-failure events in HFpEF with obesity, and SURPASS-2 — although a T2D glycemic trial — first quantified tirzepatide's weight-loss advantage over semaglutide. Every PMID below was verified live via PubMed esummary on the lastVerified date.
Ranked papers
#1SURMOUNT-1
Jastreboff AM, Aronne LJ, Ahmad NN, et al. · N Engl J Med · 2022
Primary endpoint: Body weight change at 72 weeks
The pivotal SURMOUNT-1 trial randomized 2,539 adults with obesity (BMI ≥30, no diabetes) to tirzepatide 5 mg, 10 mg, 15 mg, or placebo for 72 weeks. The highest dose produced −20.9% body weight versus −3.1% on placebo — the largest weight reduction ever recorded for a non-surgical obesity intervention at the time. Roughly 57% of participants on 15 mg lost ≥20% body weight. This trial drove the November 2023 FDA approval of Zepbound and reset the benchmark for GLP-1 obesity efficacy.
PMID 35658024 ↗NCT04184622 ↗DOI 10.1056/NEJMoa2206038 ↗
#2SURMOUNT-2
Garvey WT, Frias JP, Jastreboff AM, et al. · Lancet · 2023
Primary endpoint: Body weight change at 72 weeks
SURMOUNT-2 enrolled 938 adults with overweight or obesity AND type 2 diabetes — a population that typically loses less weight on incretin therapy. Tirzepatide 10 mg produced −13.4% body weight and 15 mg produced −15.7% versus −3.3% on placebo. A1C dropped about 2.1 percentage points. Established that tirzepatide retains roughly two-thirds of its obesity-trial weight effect in T2D and confirmed dual cardiometabolic benefit, supporting the case for Zepbound in T2D patients beyond Mounjaro's glycemic indication.
PMID 37385275 ↗NCT04657003 ↗DOI 10.1016/S0140-6736(23)01200-X ↗
#3SURMOUNT-3
Wadden TA, Chao AM, Machineni S, et al. · Nat Med · 2023
Primary endpoint: Body weight change from randomization to week 72
SURMOUNT-3 used a 12-week intensive-lifestyle run-in (low-calorie diet plus behavioral therapy) before randomizing 579 participants who had already lost ≥5% to tirzepatide or placebo for 72 more weeks. After the run-in, tirzepatide added a further −18.4% weight loss versus +2.5% regain on placebo — total mean loss from baseline ~26%. Established that GLP-1/GIP therapy compounds rather than competes with lifestyle interventions, an important finding for prior-authorization criteria requiring documented lifestyle trials.
PMID 37840095 ↗NCT04657016 ↗DOI 10.1038/s41591-023-02597-w ↗
#4SURMOUNT-4
Aronne LJ, Sattar N, Horn DB, et al. · JAMA · 2024
Primary endpoint: Percent change in body weight from week 36 to week 88
SURMOUNT-4 enrolled 670 participants who had already lost ~20.9% body weight on tirzepatide during a 36-week open-label run-in, then randomized them to continued tirzepatide or placebo. Continuing tirzepatide produced an additional −5.5% loss; switching to placebo caused +14.0% regain. Crystallized the chronic-disease framing that defines modern obesity medicine: stopping a dual GIP/GLP-1 reverses most of the weight loss within a year — physiologically identical to discontinuing antihypertensive therapy.
PMID 38078870 ↗NCT04660643 ↗DOI 10.1001/jama.2023.24945 ↗
#5SURMOUNT-5
Aronne LJ, Horn DB, le Roux CW, et al. · N Engl J Med · 2025
Primary endpoint: Percent change in body weight at week 72
SURMOUNT-5 is the first dedicated head-to-head obesity trial between the two FDA-approved GLP-1-class agents. 751 adults with obesity (no diabetes) were randomized to tirzepatide (max-tolerated 10 or 15 mg) versus semaglutide 2.4 mg for 72 weeks. Tirzepatide produced −20.2% body weight versus −13.7% on semaglutide — a 6.5-percentage-point absolute advantage, roughly 47% greater relative weight loss. Cemented tirzepatide as the most potent obesity pharmacotherapy and reshaped first-line GLP-1 selection.
PMID 40353578 ↗NCT05822830 ↗DOI 10.1056/NEJMoa2416394 ↗
#6SURMOUNT-CN
Zhao L, Cheng Z, Lu Y, et al. · JAMA · 2024
Primary endpoint: Body weight change at week 52
SURMOUNT-CN randomized 210 Chinese adults with obesity (or overweight with weight-related comorbidity) to tirzepatide 10 mg, 15 mg, or placebo for 52 weeks. Tirzepatide produced −13.6% (10 mg) and −17.5% (15 mg) versus +2.3% on placebo. Effect sizes are comparable to SURMOUNT-1 despite the lower-BMI Asian population, addressing a long-standing question about whether GIP/GLP-1 agonists work in populations with lower baseline obesity. Supported Eli Lilly's 2024 China NMPA filing for tirzepatide for obesity.
PMID 38819983 ↗NCT05024032 ↗DOI 10.1001/jama.2024.9217 ↗
#7SURMOUNT-OSA
Malhotra A, Grunstein RR, Fietze I, et al. · N Engl J Med · 2024
Primary endpoint: Change in apnea-hypopnea index (AHI) at week 52
SURMOUNT-OSA enrolled 469 adults with moderate-to-severe obstructive sleep apnea and obesity across two trials (one CPAP-using, one not). Tirzepatide reduced apnea-hypopnea index by 25-29 events/hour versus 5-6 on placebo — roughly a 55-60% relative reduction — alongside 17-20% body-weight loss. Drove the December 2024 FDA approval of Zepbound for OSA, making tirzepatide the first medication of any class approved to treat obstructive sleep apnea. Major insurance-coverage catalyst for adults with OSA but BMI <30.
PMID 38912654 ↗NCT05412004 ↗DOI 10.1056/NEJMoa2404881 ↗
#8SYNERGY-NASH
Loomba R, Hartman ML, Lawitz EJ, et al. · N Engl J Med · 2024
Primary endpoint: MASH resolution without worsening of fibrosis at 52 weeks
SYNERGY-NASH randomized 190 biopsy-confirmed MASH (formerly NASH) patients with stage F2/F3 fibrosis to tirzepatide 5/10/15 mg or placebo for 52 weeks. MASH resolution without fibrosis worsening occurred in 44-62% of tirzepatide arms versus 10% on placebo. Body weight dropped 10-15%. Established tirzepatide as the second drug with clear hepatology benefit (after resmetirom) and the first GIP/GLP-1 to demonstrate phase-2 efficacy in MASH, supporting an ongoing phase 3 program.
PMID 38856224 ↗NCT04166773 ↗DOI 10.1056/NEJMoa2401943 ↗
#9SUMMIT
Packer M, Zile MR, Kramer CM, et al. · N Engl J Med · 2025
Primary endpoint: Composite of cardiovascular death or worsening heart failure event, and change in KCCQ-CSS at week 52
The SUMMIT trial randomized 731 patients with heart failure with preserved ejection fraction (HFpEF) and obesity to tirzepatide or placebo. Tirzepatide cut the composite of cardiovascular death or worsening heart failure events by 38% (HR 0.62) and improved KCCQ-CSS by 6.9 points more than placebo, alongside ~14% body-weight loss. Established tirzepatide as HFpEF disease-modifying therapy in obese phenotypes — complementing STEP-HFpEF for semaglutide — and reframed obesity as a treatable HF risk factor.
PMID 39555826 ↗NCT04847557 ↗DOI 10.1056/NEJMoa2410027 ↗
#10SURPASS-2
Frías JP, Davies MJ, Rosenstock J, et al. · N Engl J Med · 2021
Primary endpoint: Change in glycated hemoglobin at 40 weeks (body weight key secondary)
SURPASS-2 was the first head-to-head between tirzepatide and semaglutide — designed as a glycemic-control trial in 1,879 T2D adults but reporting body weight as a key secondary endpoint. Tirzepatide produced −7.6, −9.3, and −11.2 kg at 5, 10, and 15 mg versus −5.7 kg on semaglutide 1 mg over 40 weeks, while also delivering stronger A1C reductions. Provided the earliest randomized signal that the GIP/GLP-1 dual mechanism produces greater weight loss than GLP-1 alone — a hypothesis SURMOUNT-5 later confirmed at obesity doses.
PMID 34170647 ↗NCT03987919 ↗DOI 10.1056/NEJMoa2107519 ↗
About this list
We curate ranked, citation-anchored PubMed paper lists for the most-searched questions in obesity medicine. Every PMID was verified via the NCBI PubMed esummary endpoint on 2026-05-27 — we do not cite from training data or memory. Each paper card links directly to PubMed and to ClinicalTrials.gov where applicable.
Browse our full index of research lists or our long-form research articles.
See also: our tirzepatide overview page.