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Tirzepatide research

What published studies found for Tirzepatide: 8 papers, 8 in humans, with sample sizes and key results, plus 234 registered clinical trials.

Strong human evidence

Why: Approved drug; many large phase 3 RCTs (e.g. SURMOUNT-1, 2,539 people) show 15-21% weight loss and better glucose control.

Tirzepatide (a dual GIP/GLP-1 receptor agonist) is backed by many large phase 3 human RCTs showing roughly 15-21% average weight loss at 72 weeks, better glucose control in type 2 diabetes, and benefits in sleep apnea and heart failure with preserved ejection fraction; gastrointestinal side effects are common and weight is substantially regained after stopping.

✓ 7 positive~ 1 mixed

Most lost weight returns after stopping treatment (SURMOUNT-4).

US compounding: FDA-approved drug. FDA-approved (Mounjaro, Zepbound). The shortage ended in December 2024, so pharmacies can no longer make copies of it; compounding is limited to genuine patient-specific changes. Status for every peptide.

Browse and filter these papers Tirzepatide prices and vendors

Reported side effects

commonNausea, diarrhea, vomiting and other GI events (mostly mild-moderate, during dose escalation) [ref] [ref] [ref] [ref] [ref]
uncommonDiscontinuation due to adverse events [ref] [ref] [ref]
uncommonSerious adverse events [ref] [ref]
uncommonHypoglycemia (in type 2 diabetes) [ref]

Registered clinical trials

234 trials of Tirzepatide on ClinicalTrials.gov: 145 active, 82 completed, 45 with posted results. Registered trials include ones that haven't published yet.

Trial	Status	Phase	People	Sponsor
Comparative Effectiveness of Tirzepatide vs Semaglutide in Participants With Type 2 Diabetes and Heart Failure With Preserved Ejection FractionNCT06980623 · started 2025-01-01	Active, not recruiting	–	26,000	Brigham and Women's Hospital
A Study of Tirzepatide (LY3298176) on the Reduction on Morbidity and Mortality in Adults With ObesityNCT05556512 · started 2022-10-11	Active, not recruiting	Phase 3	15,374	Eli Lilly and Company
A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (SYNERGY-Outcomes)NCT07165028 · started 2025-10-15	Recruiting	Phase 3	4,500	Eli Lilly and Company
A Study of Tirzepatide (LY3298176) Compared With Standard of Care in Adult Participants With Obesity and Without Diabetes (SURMOUNT-REAL UK)NCT07247084 · started 2025-11-24	Recruiting	Phase 4	3,000	Eli Lilly and Company
Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo in Participants Who Are Either Obese or Overweight With Weight-Related Comorbidities (SURMOUNT-1)NCT07481747 · started 2026-02-02	Recruiting	Phase 3	2,539	Hudson Biotech
GLP-1 Medication & Behavioral Health Programs on Weight & Metabolic Outcomes: FLOURISH and THRIVE Prospective Cohort StudyNCT07588984 · started 2026-04-30	Not yet recruiting	–	2,310	Noom Inc.
Real-world Effectiveness and Dosing Patterns of Tirzepatide in People With ObesityNCT07504172 · started 2026-04-01	Not yet recruiting	–	1,700	Radboud University Medical Center
A Master Protocol Study (LY900038) of Multiple Intervention-Specific-Appendices (ISAs) in Adult Participants With Obesity or OverweightNCT06143956 · started 2023-11-17	Recruiting	Phase 2	1,481	Eli Lilly and Company
The Long COVID Treatment TrialNCT07128082 · started 2025-10-30	Active, not recruiting	Phase 2	1,000	Scripps Translational Science Institute
A Study of Tirzepatide (LY3298176) Compared With Placebo in Adults With Type 1 Diabetes and Obesity or OverweightNCT06914895 · started 2025-04-25	Active, not recruiting	Phase 3	905	Eli Lilly and Company
A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have ObesityNCT06662383 · started 2024-11-01	Active, not recruiting	Phase 3	800	Eli Lilly and Company
A Study of Tirzepatide Compared With Intensified Conventional Care in Adult Participants With Type 2 DiabetesNCT05433584 · started 2022-08-01	Active, not recruiting	Phase 4	780	Eli Lilly and Company

All 234 Tirzepatide trials, with countries and recruiting status

Meta-analyses & systematic reviews

✓ Positivemeta-analysisNat Med · 2022

Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.

7 randomized trials (SURPASS); 4,887 on tirzepatide and 2,328 controlsPre-specified cardiovascular meta-analysis with stratified Cox model

Pooling 7 SURPASS trials (7,215 participants), tirzepatide did not increase major cardiovascular events vs controls (HR 0.80, 95% CI 0.57-1.11).

Key resultHR for MACE-4 0.80 (95% CI 0.57-1.11); cardiovascular death HR 0.90 (95% CI 0.50-1.61); all-cause death HR 0.80 (95% CI 0.51-1.25)

Studied: Participants with type 2 diabetes in seven SURPASS trials of at least 26 weeks
Compared with: Pooled control groups
Main outcome: Time to first confirmed MACE-4
Authors' conclusion: Tirzepatide did not increase the risk of major cardiovascular events in participants with type 2 diabetes versus controls.
Limitations: Few events (142 with MACE-4); CIs include both benefit and harm.

PubMed 35210595 DOI Free full text

Fig. 2: Adjusted Kaplan–Meier plot of pooled tirzepatide versus pooled comparator effect on time to first occurrence of adjudication-confirmed MACE- — Fig. 2. From PMC8938269, CC BY (terms); resized.

Human studies

✓ Positivehuman RCTN Engl J Med · 2022

Tirzepatide Once Weekly for the Treatment of Obesity.

n = 2,539 humansPhase 3 double-blind randomized controlled trial (SURMOUNT-1)72 weeks including 20-week dose escalation

In 2539 adults with obesity without diabetes (SURMOUNT-1), 72 weeks of tirzepatide reduced weight by 15.0-20.9% depending on dose vs 3.1% with placebo; GI events were the most common adverse effects.

Key resultMean weight change at week 72 was -15.0% (5 mg), -19.5% (10 mg), -20.9% (15 mg) vs -3.1% with placebo (P<0.001 for all comparisons)

Studied: Adults with BMI of 30 or more, or 27 or more with at least one weight-related complication, excluding diabetes
Compared with: Placebo
Main outcome: Percent change in weight and weight reduction of 5% or more
Sample: 2539 adults randomized 1:1:1:1
Authors' conclusion: In this 72-week trial in people with obesity, tirzepatide 5, 10 or 15 mg once weekly produced substantial and sustained reductions in body weight; adverse events were mainly gastrointestinal.
Limitations: Adverse events caused discontinuation in 4.3%, 7.1%, 6.2% (5, 10, 15 mg) vs 2.6% placebo.

PubMed 35658024 DOI

✓ Positivehuman RCTN Engl J Med · 2021

Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.

n = 1,879 humansOpen-label phase 3 randomized trial (SURPASS-2)40 weeks

In 1879 people with type 2 diabetes (SURPASS-2), tirzepatide lowered HbA1c and weight more than semaglutide 1 mg; nausea 17-22%, diarrhea 13-16%, serious adverse events 5-7% vs 3%.

Key resultHbA1c change -2.01, -2.24 and -2.30 percentage points with tirzepatide 5, 10, 15 mg vs -1.86 with semaglutide (difference vs semaglutide -0.15 [P = 0.02], -0.39 and -0.45 [both P<0.001])

Studied: Patients with type 2 diabetes (mean HbA1c 8.28%)
Compared with: Semaglutide 1 mg
Main outcome: Change in glycated hemoglobin from baseline
Sample: 1879 patients randomized 1:1:1:1
Authors' conclusion: Tirzepatide at all doses was noninferior and superior to semaglutide for the change in HbA1c at 40 weeks in type 2 diabetes.
Limitations: Open-label design.

PubMed 34170647 DOI

✓ Positivehuman RCTN Engl J Med · 2025

Tirzepatide for Obesity Treatment and Diabetes Prevention.

n = 1,032 humansPhase 3 double-blind randomized controlled trial (SURMOUNT-1, prediabetes subgroup)176 weeks plus 17-week off-treatment period

Over 176 weeks in 1032 people with obesity and prediabetes, tirzepatide reduced weight 12.3-19.7% vs 1.3% with placebo and cut progression to type 2 diabetes (1.3% vs 13.3%).

Key resultWeight change at 176 weeks -12.3% (5 mg), -18.7% (10 mg), -19.7% (15 mg) vs -1.3% placebo (P<0.001); type 2 diabetes diagnosed in 1.3% vs 13.3% (HR 0.07; P<0.001)

Studied: Adults with obesity and prediabetes
Compared with: Placebo
Main outcome: Percent change in body weight at week 176 and onset of type 2 diabetes
Sample: 1032 of 2539 SURMOUNT-1 participants had prediabetes and were analysed
Authors' conclusion: Three years of tirzepatide in persons with obesity and prediabetes produced substantial, sustained weight reduction and a markedly lower risk of progression to type 2 diabetes. No new safety signals were identified.
Limitations: Prediabetes subgroup analysis; funded by Eli Lilly.

PubMed 39536238 DOI

✓ Positivehuman RCTN Engl J Med · 2025

Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.

n = 751 humansPhase 3b open-label randomized controlled trial (SURMOUNT-5)72 weeks

In 751 adults with obesity (open-label SURMOUNT-5), tirzepatide produced -20.2% weight change at 72 weeks vs -13.7% with semaglutide.

Key resultMean weight change -20.2% (95% CI, -21.4 to -19.1) with tirzepatide vs -13.7% (95% CI, -14.9 to -12.6) with semaglutide (P<0.001)

Studied: Adults with obesity but without type 2 diabetes
Compared with: Semaglutide (maximum tolerated dose, 1.7 or 2.4 mg)
Main outcome: Percent change in weight from baseline to week 72
Sample: 751 participants randomized 1:1
Authors' conclusion: In adults with obesity without diabetes, tirzepatide was superior to semaglutide for reduction in body weight and waist circumference at week 72.
Limitations: Open-label design; funded by Eli Lilly.

PubMed 40353578 DOI

✓ Positivehuman RCTN Engl J Med · 2025

Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.

n = 731 humansInternational double-blind randomized placebo-controlled trialAt least 52 weeks; median follow-up 104 weeks

In 731 patients with HFpEF and obesity (SUMMIT), tirzepatide lowered cardiovascular death or worsening heart failure (9.9% vs 15.3%; HR 0.62) and improved quality-of-life scores; GI-related discontinuations 6.3% vs 1.4%.

Key resultDeath from cardiovascular causes or worsening heart failure in 36 patients (9.9%) vs 56 (15.3%) on placebo (HR 0.62; 95% CI 0.41 to 0.95; P = 0.026)

Studied: Patients with heart failure, ejection fraction of at least 50% and BMI of at least 30
Compared with: Placebo
Main outcome: Cardiovascular death or worsening heart-failure event; change in KCCQ-CSS at 52 weeks
Sample: 731 patients (364 tirzepatide, 367 placebo)
Authors' conclusion: Tirzepatide led to a lower risk of the composite of cardiovascular death or worsening heart failure than placebo and improved health status in these patients.
Limitations: Cardiovascular deaths alone were not reduced (8 vs 5 patients, HR 1.58; wide CI).

PubMed 39555826 DOI

~ Mixedhuman RCTJAMA · 2024

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.

n = 670 humansPhase 3 randomized withdrawal trial (SURMOUNT-4)36-week open-label lead-in then 52-week double-blind period

After 36 weeks of open-label tirzepatide (20.9% loss), those switched to placebo regained 14.0% of body weight over 52 weeks while those continuing lost a further 5.5%.

Key resultWeight change from week 36 to 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference -19.4%; 95% CI -21.2% to -17.7%; P < .001)

Studied: Adults with BMI of 30 or more, or 27 or more with a weight-related complication, excluding diabetes
Compared with: Switch to placebo
Main outcome: Mean percent change in weight from week 36 to week 88
Sample: 670 randomized after 36-week lead-in (783 enrolled in lead-in)
Authors' conclusion: Withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction.
Limitations: Only participants who completed the open-label lead-in were randomized.

PubMed 38078870 DOI Free full text

✓ Positivehuman RCTN Engl J Med · 2024

Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.

Two phase 3 trials; participant numbers not stated in abstractTwo phase 3 double-blind randomized controlled trials52 weeks

In two 52-week trials in adults with moderate-severe sleep apnea and obesity, tirzepatide reduced the apnea-hypopnea index by about 20-24 more events per hour than placebo.

Key resultTrial 1: AHI changed by -25.3 events per hour with tirzepatide vs -5.3 with placebo (difference -20.0; 95% CI -25.8 to -14.2; P<0.001); trial 2: -29.3 vs -5.5 (difference -23.8; P<0.001)

Studied: Adults with moderate-to-severe obstructive sleep apnea and obesity (trial 1 without PAP, trial 2 on PAP)
Compared with: Placebo
Main outcome: Change in apnea-hypopnea index (AHI)
Authors' conclusion: Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced AHI, body weight, hypoxic burden, hsCRP and systolic blood pressure.

PubMed 38912654 DOI Free full text

Verdicts are judged on each paper's own main outcome; grades run from A (strong human evidence) to D (little or none). Details are read from the abstracts, and figures are reproduced only from openly licensed full texts. Not medical advice.